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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>CSF1R-Related Disorder - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="CSF1R-Related Disorder">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2024/04/04">
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<meta name="citation_author" content="Jaroslaw Dulski">
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<meta name="citation_author" content="Christina Sundal">
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<meta name="citation_author" content="Zbigniew K Wszolek">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK100239/">
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<meta name="citation_keywords" content="Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis (BANDDOS)">
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<meta name="citation_keywords" content="Pigmentary Orthochromatic Leukodystrophy (POLD)">
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<meta name="citation_keywords" content="Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)">
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<meta name="citation_keywords" content="Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS)">
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<meta name="citation_keywords" content="CSF1R-Related Leukoencephalopathy">
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<meta name="citation_keywords" content="Early-Onset CSF1R-Related Disorder">
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<meta name="citation_keywords" content="Late-Onset CSF1R-Related Disorder">
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<meta name="citation_keywords" content="Macrophage colony-stimulating factor 1 receptor">
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<meta name="citation_keywords" content="CSF1R">
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<meta name="citation_keywords" content="CSF1R-Related Disorder">
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<meta name="DC.Title" content="CSF1R-Related Disorder">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Jaroslaw Dulski">
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<meta name="DC.Contributor" content="Christina Sundal">
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<meta name="DC.Contributor" content="Zbigniew K Wszolek">
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<meta name="DC.Date" content="2024/04/04">
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<meta name="description" content="The spectrum of CSF1R-related disorder ranges from early-onset disease (age <18 years) to late-onset disease (age ≥18 years). Early-onset disease is associated with hypotonia, delayed acquisition of developmental milestones, and non-neurologic manifestations (such as skeletal abnormalities); both early- and late-onset disease have similar neurodegenerative involvement. Most affected individuals eventually become bedridden with spasticity, rigidity, and loss of the ability to walk. They lose speech and voluntary movement and appear to be generally unaware of their surroundings. The last stage of disease progresses to a vegetative state with presence of primitive reflexes, such as visual and tactile grasp, mouth-opening reflex, and sucking reflex. Death most commonly results from pneumonia or other infections. About 500 individuals with CSF1R-related disorder have been reported to date.">
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<meta name="og:title" content="CSF1R-Related Disorder">
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<meta name="og:description" content="The spectrum of CSF1R-related disorder ranges from early-onset disease (age <18 years) to late-onset disease (age ≥18 years). Early-onset disease is associated with hypotonia, delayed acquisition of developmental milestones, and non-neurologic manifestations (such as skeletal abnormalities); both early- and late-onset disease have similar neurodegenerative involvement. Most affected individuals eventually become bedridden with spasticity, rigidity, and loss of the ability to walk. They lose speech and voluntary movement and appear to be generally unaware of their surroundings. The last stage of disease progresses to a vegetative state with presence of primitive reflexes, such as visual and tactile grasp, mouth-opening reflex, and sucking reflex. Death most commonly results from pneumonia or other infections. About 500 individuals with CSF1R-related disorder have been reported to date.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK100239_"><span class="title" itemprop="name"><i>CSF1R</i>-Related Disorder</span></h1><p class="contribs">Dulski J, Sundal C, Wszolek ZK.</p><p class="fm-aai"><a href="#_NBK100239_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 39 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hdls.Summary" itemprop="description"><h2 id="_hdls_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>The spectrum of <i>CSF1R</i>-related disorder ranges from early-onset disease (age <18 years) to late-onset disease (age ≥18 years). Early-onset disease is associated with hypotonia, delayed acquisition of developmental milestones, and non-neurologic manifestations (such as skeletal abnormalities); both early- and late-onset disease have similar neurodegenerative involvement. Most affected individuals eventually become bedridden with spasticity, rigidity, and loss of the ability to walk. They lose speech and voluntary movement and appear to be generally unaware of their surroundings. The last stage of disease progresses to a vegetative state with presence of primitive reflexes, such as visual and tactile grasp, mouth-opening reflex, and sucking reflex. Death most commonly results from pneumonia or other infections. About 500 individuals with <i>CSF1R</i>-related disorder have been reported to date.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>CSF1R</i>-related disorder is established in a proband with suggestive findings and a heterozygous <i>CSF1R</i> pathogenic variant or biallelic <i>CSF1R</i> pathogenic variants identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Multidisciplinary care by specialists in neurology, psychotherapy, neuropsychological rehabilitation, physical therapy, occupational therapy, speech-language therapy, social services for family support, and genetic counseling.</p><p><i>Surveillance:</i> Monitoring of existing manifestations, the individual's response to supportive care, and the emergence of new manifestations as specified by the multidisciplinary care providers.</p><p><i>Agents/circumstances to avoid:</i> For individuals with gait problems and cognitive decline, sedatives, antipsychotics, and other medications that may decrease alertness and increase the risk of falling should be used cautiously.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Early-onset <i>CSF1R</i>-related disorder is typically caused by biallelic pathogenic variants and inherited in an autosomal recessive manner; rarely, early-onset <i>CSF1R</i>-related disorder may be caused by a heterozygous pathogenic variant. Late-onset <i>CSF1R</i>-related disorder is typically caused by a heterozygous pathogenic variant and inherited in an autosomal dominant manner; rarely, late-onset <i>CSF1R</i>-related disorder may be caused by biallelic <i>CSF1R</i> pathogenic variants. While biallelic pathogenic variants are usually associated with early-onset disease and heterozygous pathogenic variants are usually associated with late-onset disease, definitive prediction of phenotype based on <i>CSF1R</i> genotype is not possible at this time.</p><p><i>Autosomal recessive inheritance:</i> The parents of an individual with <i>CSF1R</i>-related disorder caused by biallelic pathogenic variants are presumed to be heterozygous for a <i>CSF1R</i> pathogenic variant. If both parents are known to be heterozygous for a pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial <i>CSF1R</i> pathogenic variants. Sibs who inherit the same biallelic <i>CSF1R</i> pathogenic variants do not necessarily have the same clinical manifestations early in the disease course; however, in the end stage, all individuals with <i>CSF1R</i>-related disorder typically have devastating neurologic involvement. The heterozygous sibs of an individual with <i>CSF1R</i>-related disorder caused by biallelic pathogenic variants are typically asymptomatic.</p><p><i>Autosomal dominant inheritance:</i> Many individuals with <i>CSF1R-</i>related disorder caused by a heterozygous pathogenic variant have an affected parent. Some individuals with <i>CSF1R</i>-related disorder caused by a heterozygous pathogenic variant represent a simplex case; such individuals may have the disorder as the result of a pathogenic variant that occurred <i>de novo</i> in the proband; a pathogenic variant inherited from a mosaic parent; or a pathogenic variant inherited from an asymptomatic heterozygous parent. Each child of an individual with a heterozygous <i>CSF1R</i> pathogenic variant has a 50% chance of inheriting the pathogenic variant. Family members who are heterozygous for the same <i>CSF1R</i> pathogenic variant do not necessarily have the same clinical manifestations early in the disease course; however, in the end stage, all individuals with <i>CSF1R</i>-related disorder typically have devastating neurologic involvement.</p><p>Once the <i>CSF1R</i> pathogenic variant(s) have been identified in an affected family member, predictive testing for at-risk relatives and prenatal and preimplantation genetic testing for <i>CSF1R</i>-related disorder are possible.</p></div></div><div id="hdls.GeneReview_Scope"><h2 id="_hdls_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTcsf1rrelateddisorderphenotypic"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_phenotypic/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobhdlsTcsf1rrelateddisorderphenotypic"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.csf1rrelated_disorder_phenotypic"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_phenotypic/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderphenotypic">Table</a></h4><p class="float-caption no_bottom_margin"><i>CSF1R</i>-Related Disorder: Phenotypic Continuum </p></div></div></div><div id="hdls.Diagnosis"><h2 id="_hdls_Diagnosis_">Diagnosis</h2><div id="hdls.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>CSF1R</i>-related disorder should be suspected in a proband with the following clinical and neuroimaging findings (that present in an age-dependent manner) and family history [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</p><div id="hdls.Early_Onset_age__18_years"><h4>Early Onset (age <18 years)</h4><p><b>Clinical findings.</b> Most common neurologic manifestations include:</p><ul><li class="half_rhythm"><div>Speech disturbances</div></li><li class="half_rhythm"><div>Developmental delay and/or cognitive decline</div></li><li class="half_rhythm"><div>Spasticity with abnormal reflexes and other pyramidal signs</div></li><li class="half_rhythm"><div>Parkinsonism</div></li><li class="half_rhythm"><div>Dysphagia</div></li><li class="half_rhythm"><div>Seizures</div></li></ul><p><b>Radiographic features</b> [<a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>]</p><ul><li class="half_rhythm"><div>Diffuse osteosclerosis of the craniofacial bones, most prominent in the skull base</div></li><li class="half_rhythm"><div>Platyspondyly and sclerosis of the vertebral bodies</div></li><li class="half_rhythm"><div>Sclerotic pelvic bones most prominent in the iliac bodies, sclerosis of proximal femora</div></li><li class="half_rhythm"><div>Tubular bones: diaphyseal sclerosis and metaphyseal radiolucency with metaphyseal undermodeling</div></li></ul><p><b>Neuroimaging findings.</b> The spectrum of brain abnormalities include the following [<a class="bibr" href="#hdls.REF.monies.2017.1144" rid="hdls.REF.monies.2017.1144">Monies et al 2017</a>, <a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>, <a class="bibr" href="#hdls.REF.oosterhof.2019.936" rid="hdls.REF.oosterhof.2019.936">Oosterhof et al 2019</a>, <a class="bibr" href="#hdls.REF.breningstall.2020.44" rid="hdls.REF.breningstall.2020.44">Breningstall & Asis 2020</a>, <a class="bibr" href="#hdls.REF.tamhankar.2020.302" rid="hdls.REF.tamhankar.2020.302">Tamhankar et al 2020</a>, <a class="bibr" href="#hdls.REF.k_nd__.2021.1888" rid="hdls.REF.k_nd__.2021.1888">Kındış et al 2021</a>, <a class="bibr" href="#hdls.REF.sriram.2022.311" rid="hdls.REF.sriram.2022.311">Sriram at al 2022</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>]:</p><ul><li class="half_rhythm"><div class="half_rhythm">Progressive bilateral white matter lesions that are hyperintense on T<sub>2</sub>-weighted and FLAIR images, and hypointense on T<sub>1</sub>-weighted images in the deep, subcortical, and periventricular areas that are often asymmetric, especially early in the disease course. Early lesions are patchy and focal but with time become confluent. T<sub>2</sub>-weighted and FLAIR hyperintensities are present in other areas, including the corpus callosum and corticospinal tracts.</div></li><li class="half_rhythm"><div class="half_rhythm">Calcifications</div><div class="half_rhythm">Note: Calcifications are poorly visible or not at all on conventional (1.5- or 3-Tesla) brain MRI; however, they may be appreciated on 7-Tesla brain MRI, which to date has limited availability. Calcifications are also detectable by thin-slice brain computed tomography (CT), which is available in routine clinical settings. Calcifications may be better visualized by 1 mm sections together with sagittal reconstructions.</div></li><li class="half_rhythm"><div class="half_rhythm">Cerebral atrophy</div></li><li class="half_rhythm"><div class="half_rhythm">Ventriculomegaly</div></li><li class="half_rhythm"><div class="half_rhythm">Agenesis or thinning of the corpus callosum</div></li><li class="half_rhythm"><div class="half_rhythm">Dandy-Walker malformation</div></li><li class="half_rhythm"><div class="half_rhythm">Malformations of cortical development (thinning of the cortex with poor white-gray distinction and underdeveloped gyration)</div></li></ul></div><div id="hdls.Late_Onset_age__18_years"><h4>Late Onset (age ≥18 years)</h4><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Progressive neurologic decline beginning at mean age of 40±10 years in women and 47±11 years in men</div></li><li class="half_rhythm"><div>Neurologic manifestations</div><ul><li class="half_rhythm"><div>Speech disturbances</div></li><li class="half_rhythm"><div>Cognitive decline</div></li><li class="half_rhythm"><div>Neurobehavioral/psychiatric manifestations (behavioral and personality changes)</div></li><li class="half_rhythm"><div>Spasticity</div></li><li class="half_rhythm"><div>Parkinsonism</div></li><li class="half_rhythm"><div>Seizures</div></li></ul></li></ul><p><b>Neuroimaging findings.</b> Typical brain abnormalities on imaging include the following [<a class="bibr" href="#hdls.REF.van_gerpen.2008.925" rid="hdls.REF.van_gerpen.2008.925">Van Gerpen et al 2008</a>, <a class="bibr" href="#hdls.REF.sundal.2012.566" rid="hdls.REF.sundal.2012.566">Sundal et al 2012</a>, <a class="bibr" href="#hdls.REF.bender.2014.2351" rid="hdls.REF.bender.2014.2351">Bender et al 2014</a>, <a class="bibr" href="#hdls.REF.konno.2014.139" rid="hdls.REF.konno.2014.139">Konno et al 2014</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2022b.1110" rid="hdls.REF.dulski.2022b.1110">Dulski et al 2022b</a>, <a class="bibr" href="#hdls.REF.mickeviciute.2022.269" rid="hdls.REF.mickeviciute.2022.269">Mickeviciute et al 2022</a>]:</p><ul><li class="half_rhythm"><div class="half_rhythm">Progressive bilateral white matter lesions that are hyperintense on T<sub>2</sub>-weighted and FLAIR images, and hypointense on T<sub>1</sub>-weighted images in the deep, subcortical, and periventricular areas that are often asymmetric, especially early in the disease course. Early lesions are patchy and focal but with time become confluent. T<sub>2</sub>-weighted and FLAIR hyperintensities are present in other areas, including the corpus callosum and corticospinal tracts.</div></li><li class="half_rhythm"><div class="half_rhythm">Cerebral atrophy, including thinning of the corpus callosum</div></li><li class="half_rhythm"><div class="half_rhythm">Calcifications are observed in the white matter in up to half of affected individuals, and frequently have a characteristic "stepping-stone appearance" in the frontal pericallosal area and punctate appearance in the frontal white matter (adjacent to the anterior horns of the lateral ventricles) and the parietal subcortical white matter [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>].</div><div class="half_rhythm">Note: Calcifications are poorly visible or not at all on conventional (1.5- or 3-Tesla) brain MRI; however, they may be appreciated on 7-Tesla brain MRI, which to date has limited availability. Calcifications are also detectable by thin-slice brain computed tomography (CT), which is available in routine clinical settings. Calcifications may be better visualized by 1 mm sections together with sagittal reconstructions.</div></li></ul></div><div id="hdls.Laboratory_Findings"><h4>Laboratory Findings</h4><p>In both early- and late-onset <i>CSF1R</i>-related disorder, cerebrospinal fluid (CSF) is unremarkable (i.e., normal cell count, glucose concentration, and proteins; no inflammatory cells; typically, normal isoelectric focusing and no oligoclonal bands). CSF studies are primarily used to evaluate for other diseases [<a class="bibr" href="#hdls.REF.saitoh.2019.22" rid="hdls.REF.saitoh.2019.22">Saitoh et al 2019</a>].</p></div><div id="hdls.Family_History"><h4>Family History</h4><p>Family history for early- and late-onset <i>CSF1R</i>-related disorder may suggest autosomal dominant inheritance (e.g., affected males and females in multiple generations), autosomal recessive inheritance, or the proband may represent a simplex case (i.e., the only family member known to be affected). A positive family history is more likely to be seen in probands with late-onset disease (i.e., age ≥18 years). The absence of a known family history does not preclude the diagnosis.</p></div></div><div id="hdls.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>CSF1R</i>-related disorder <b>is established</b> in a proband with <a href="#hdls.Suggestive_Findings">suggestive findings</a> and a heterozygous <i>CSF1R</i> pathogenic (or likely pathogenic) variant or biallelic <i>CSF1R</i> pathogenic (or likely pathogenic) variants identified by molecular genetic testing (see <a href="/books/NBK100239/table/hdls.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobhdlsTmoleculargenetictestingusedin">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#hdls.REF.richards.2015.405" rid="hdls.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of a heterozygous or biallelic <i>CSF1R</i> variant(s) of uncertain significance does not establish or rule out the diagnosis.</p><p><b>Molecular genetic testing approaches</b> can include a combination of <b>gene-targeted testing</b> (multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#hdls.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#hdls.Option_2">Option 2</a>).</p><p>Note: Single-gene testing (sequence analysis of <i>CSF1R</i>, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.</p><div id="hdls.Option_1"><h4>Option 1</h4><p><b>A multigene panel</b> that includes <i>CSF1R</i> and other genes of interest (in probands with early or late onset, a leukodystrophy and leukoencephalopathy or Parkinson disease and parkinsonism panel; in probands with early onset specifically, a skeletal disorders or brain malformations panel; in probands with late onset specifically, a movement disorders or dementia panel; see <a href="#hdls.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="hdls.Option_2"><h4>Option 2</h4><p><b>Comprehensive genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. To date, the majority of <i>CSF1R</i> pathogenic variants reported (e.g., missense, nonsense) are within the coding region and are likely to be identified on exome sequencing. Of note, several splicing variants beyond the canonical splice site have been identified [<a class="bibr" href="#hdls.REF.rademakers.2011.200" rid="hdls.REF.rademakers.2011.200">Rademakers et al 2011</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.wu.2022.3265" rid="hdls.REF.wu.2022.3265">Wu et al 2022</a>] that may be detected by genome sequencing.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTmoleculargenetictestingusedin"><a href="/books/NBK100239/table/hdls.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobhdlsTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.molecular_genetic_testing_used_in"><a href="/books/NBK100239/table/hdls.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobhdlsTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>CSF1R</i>-Related Disorder </p></div></div></div></div></div><div id="hdls.Clinical_Characteristics"><h2 id="_hdls_Clinical_Characteristics_">Clinical Characteristics</h2><div id="hdls.Clinical_Description"><h3>Clinical Description</h3><p>The spectrum of <i>CSF1R</i>-related disorder ranges from early-onset disease (age <18 years) to late-onset disease (age ≥18 years). Early-onset disease is more often associated with non-neurologic manifestations (such as skeletal abnormalities), whereas both early- and late-onset disease have similar neurodegenerative involvement.</p><p>Information on about 500 affected individuals has been reported to date. The following description of the phenotypic features associated with <i>CSF1R</i>-related disorder is based on reports of about 150 individuals (most of whom have late-onset disease) [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>]. See <a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_frequency_o/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderfrequencyo">Table 2</a> for a summary of the frequency of select features by age of onset.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTcsf1rrelateddisorderfrequencyo"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_frequency_o/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobhdlsTcsf1rrelateddisorderfrequencyo"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.csf1rrelated_disorder_frequency_o"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_frequency_o/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderfrequencyo">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>CSF1R</i>-Related Disorder: Frequency of Select Features by Age of Onset </p></div></div><div id="hdls.Findings_Unique_to_EarlyOnset_CSF1R"><h4>Findings Unique to Early-Onset <i>CSF1R</i>-Related Disorder</h4><p><b>Infantile-onset hypotonia</b> ("floppy baby syndrome") is characterized by decreased muscle tone, frequently accompanied by developmental delay, hyperextensibility of the joints, and postural disturbances [<a class="bibr" href="#hdls.REF.kaler.2020.e6922" rid="hdls.REF.kaler.2020.e6922">Kaler et al 2020</a>]. It may disappear in adolescence.</p><p><b>Developmental delay</b> may be observed from birth with delayed reaching of milestones, or begin in childhood with the loss of previously acquired milestones or regression in development [<a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et. al 2023c</a>].</p><p><b>Skeletal abnormalities,</b> reported in limited detail, include bone fragility and susceptibility to fracture beginning in childhood, short extremities or proportionate short stature usually of variable severity, and bone sclerosis (which, when involving the skull, has been associated with narrowing of the optic foramen and secondary optic atrophy) [<a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>, <a class="bibr" href="#hdls.REF.oosterhof.2019.936" rid="hdls.REF.oosterhof.2019.936">Oosterhof et al 2019</a>]. Radiographs can show pelvic bone sclerosis, vertebral sclerosis, platyspondyly, undermodeling of the tubular bones with widened metaphysis, radiolucent metaphysis, constricted diaphysis, and sclerotic diaphysis).</p><p><b>Dysmorphic features,</b> reported in limited detail, may include abnormal size and shape of the skull (macrocephaly, bony prominences), epicanthus, ptosis, bulbous nose, high-arched palate, and chest deformities (bell shaped, pectus carinatum) [<a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>].</p></div><div id="hdls.Findings_Shared_by_Early_and_LateOn"><h4>Findings Shared by Early- and Late-Onset <i>CSF1R</i>-Related Disorder</h4><p><b>Speech abnormalities</b> usually include dysarthria and/or aphasia. Of note, not infrequently, dysarthria co-occurs with aphasia.</p><p>Dysarthria denotes slurring of speech and affects more than 50% of individuals [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>, <a class="bibr" href="#hdls.REF.wu.2024.798" rid="hdls.REF.wu.2024.798">Wu et al 2024</a>]. It is most often of mixed type, including spastic, hypokinetic with cerebellar features that may manifest as a strained voice, hypophonia (soft speech), slow rate of speech, monotonicity, excessive or reduced stress on syllables, or inappropriate variation in pitch.</p><p>Aphasia refers to disturbances of language production (motor or non-fluent aphasia) or comprehension (sensory or fluent aphasia). Although there are no systematic studies on the subtypes of aphasia in <i>CSF1R</i>-related disorder, limited evidence suggests the motor subtype is more common [<a class="bibr" href="#hdls.REF.lee.2015.817" rid="hdls.REF.lee.2015.817">Lee et al 2015</a>, <a class="bibr" href="#hdls.REF.daida.2017.2507" rid="hdls.REF.daida.2017.2507">Daida et al 2017</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.jiang.2022.902067" rid="hdls.REF.jiang.2022.902067">Jiang et al 2022</a>].</p><p><b>Cognitive impairment</b> occurs to some extent in virtually all individuals and may be the first manifestation or appear later in the disease course. The major components of cognitive decline are processing speed, executive function, word retrieval, and visual problem solving [<a class="bibr" href="#hdls.REF.rush.2023.1155387" rid="hdls.REF.rush.2023.1155387">Rush et al 2023</a>]. These progressive findings are the primary cause of loss of independence in activities of daily living [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.konno.2018.142" rid="hdls.REF.konno.2018.142">Konno et al 2018</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>, <a class="bibr" href="#hdls.REF.rush.2023.1155387" rid="hdls.REF.rush.2023.1155387">Rush et al 2023</a>].</p><p><b>Pyramidal signs</b> include spasticity, hyperreflexia, extensor plantar response, hemiparesis, and/or quadriparesis.</p><p>
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<b>Extrapyramidal signs</b>
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</p><ul><li class="half_rhythm"><div>Parkinsonism (hypomimia, rigidity, bradykinesia, shuffling gait, postural instability, resting and/or kinetic tremor) is common and most often of the non-tremor dominant subtype [<a class="bibr" href="#hdls.REF.sundal.2013.869" rid="hdls.REF.sundal.2013.869">Sundal et al 2013</a>].</div></li><li class="half_rhythm"><div>Dystonia may be isolated to one body part, one side of the body, or generalized. It may be a part of a corticobasal syndrome [<a class="bibr" href="#hdls.REF.baba.2006.300" rid="hdls.REF.baba.2006.300">Baba et al 2006</a>, <a class="bibr" href="#hdls.REF.sundal.2013.869" rid="hdls.REF.sundal.2013.869">Sundal et al 2013</a>].</div></li><li class="half_rhythm"><div>Myoclonus may resemble tremor in individuals with polymyoclonus (repetitive low-amplitude myoclonus).</div></li><li class="half_rhythm"><div>Dyskinesia and chorea may also be observed in some individuals [<a class="bibr" href="#hdls.REF.van_der_knaap.2000.463" rid="hdls.REF.van_der_knaap.2000.463">van der Knaap et al 2000</a>, <a class="bibr" href="#hdls.REF.baba.2006.300" rid="hdls.REF.baba.2006.300">Baba et al 2006</a>, <a class="bibr" href="#hdls.REF.sundal.2013.869" rid="hdls.REF.sundal.2013.869">Sundal et al 2013</a>].</div></li></ul><p><b>Cerebellar involvement</b> can include ataxia (lack of coordination), dysmetria (imprecise movement control), cerebellar tremor (involuntary shaking during movement), dysdiadochokinesia (difficulty with rapid alternating movements), scanning speech (abnormal speech pattern), and nystagmus (involuntary eye movement) [<a class="bibr" href="#hdls.REF.wu.2024.798" rid="hdls.REF.wu.2024.798">Wu et al 2024</a>].</p><p>Notably, in most individuals motor signs may occur in varying combinations (e.g., pyramidal and extrapyramidal signs). For instance, it is common to observe increased muscle tone of mixed spastic-rigid type.</p><p><b>Dysphagia</b> (swallowing disturbances) is more common in individuals with severe neurologic deficits [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>]. It may encompass difficulty initiating swallowing, sensation of food sticking in the throat or chest, regurgitation, coughing or choking during meals, recurrent pneumonia (due to aspiration), unintentional weight loss, and malnutrition or dehydration.</p><p><b>Sensory deficits</b> include impairment of vibration, position, touch, and pain perception as well as impairment of higher integrative sensory functions such as graphesthesia, stereognosis, and sensory neglect on double stimulation.</p><p><b>Apraxia</b> (inability to perform certain voluntary purposeful movements despite preserved ability to use the affected body part) may occur in up to one third of individuals [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>].</p><p><b>Astereognosis</b> (inability to identify objects by touch) and agraphesthesia are common. Disturbance of right-left body side recognition, a characteristic feature, is most likely due to involvement of the corpus callosum.</p><p><b>Visual disturbances</b> include homonymous quadrantanopsia or hemianopsia. These manifestations may be due to optic nerve atrophy, for which the pathophysiologic underpinnings are not understood [<a class="bibr" href="#hdls.REF.shu.2016.171" rid="hdls.REF.shu.2016.171">Shu et al 2016</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>].</p><p><b>Seizures.</b> Initial seizure types vary. Generalized seizures seem the most common and tend to occur more frequently in individuals with more severe neurologic deficits. Occasionally, they may be the first manifestation of the disease [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>].</p><p><b>Neurobehavioral/psychiatric manifestations.</b> Many individuals report anxiety and symptoms of depression [<a class="bibr" href="#hdls.REF.rush.2023.1155387" rid="hdls.REF.rush.2023.1155387">Rush et al 2023</a>]. There are some reports of findings reminiscent of the behavioral variant of frontotemporal dementia, with personality changes, executive dysfunction, and loss of judgment and insight [<a class="bibr" href="#hdls.REF.rush.2023.1155387" rid="hdls.REF.rush.2023.1155387">Rush et al 2023</a>].</p><p>Pseudobulbar affect (i.e., uncontrolled crying or laughing disproportionate to the individual's emotional state) has been reported occasionally [<a class="bibr" href="#hdls.REF.ahmed.2013.483" rid="hdls.REF.ahmed.2013.483">Ahmed & Simmons 2013</a>, <a class="bibr" href="#hdls.REF.robinson.2015.42" rid="hdls.REF.robinson.2015.42">Robinson et al 2015</a>, <a class="bibr" href="#hdls.REF.rosenstein.2022.599" rid="hdls.REF.rosenstein.2022.599">Rosenstein et al 2022</a>, <a class="bibr" href="#hdls.REF.sriram.2022.311" rid="hdls.REF.sriram.2022.311">Sriram et al 2022</a>].</p><p><b>Other.</b> On average, women develop the first manifestations of late-onset <i>CSF1R</i>-related disorder earlier (age 40 years) than men (age 47 years) [<a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>].</p><p><b>Intrafamilial variability.</b> Individuals from the same family who have the same <i>CSF1R</i> pathogenic variant(s) do not necessarily have the same clinical manifestations early in the disease course; however, in the end stage, all individuals with <i>CSF1R</i>-related disorder typically have devastating neurologic involvement.</p><p><b>Prognosis.</b> Presence of malformations of cortical development, skeletal deformities, and cognitive impairment as the initial and predominant presentation is usually associated with a worse prognosis, with faster disease progression and earlier disability [<a class="bibr" href="#hdls.REF.dulski.2022a.2778" rid="hdls.REF.dulski.2022a.2778">Dulski et al 2022a</a>, <a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al 2023c</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</p><p>Most affected individuals eventually become bedridden with spasticity and rigidity. They lose speech and voluntary movement, and appear to be generally unaware of their surroundings. In the last stage of disease progression, individuals lose their ability to walk and progress to a vegetative state. Primitive reflexes, such as visual and tactile grasp, mouth-opening reflex, and sucking reflex, are present. Death most commonly results from pneumonia or other infections.</p></div></div><div id="hdls.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been identified to date.</p></div><div id="hdls.Penetrance"><h3>Penetrance</h3><p>Penetrance is estimated to be high but not complete [<a class="bibr" href="#hdls.REF.karle.2013.2039" rid="hdls.REF.karle.2013.2039">Karle et al 2013</a>, <a class="bibr" href="#hdls.REF.sundal.2015.328" rid="hdls.REF.sundal.2015.328">Sundal et al 2015</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>].</p></div><div id="hdls.Nomenclature"><h3>Nomenclature</h3><p><b>Pathology-based terminology.</b> Prior to the molecular characterization of <i>CSF1R</i>-related disorder, pathology-based terminology – pigmentary orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with spheroids (HDLS) – was used to describe what appeared to be distinct disorders [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>]. These terms were later consolidated under a single pathology-based designation, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).</p><p><b>Gene-based terminology.</b> The molecular characterization of <i>CSF1R</i> allowed gene-based terminology to be established, i.e., <i>CSF1R</i>-related leukoencephalopathy/leukodystrophy and <i>CSF1R</i>-related ALSP.</p><p><b>Unified terminology.</b> In recognition of the shared molecular etiology and significant phenotype overlap between <i>CSF1R</i>-related leukoencephalopathy and brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS), <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al [2024]</a> proposed the designation <i>CSF1R</i>-related disorder – subdivided into early onset (age <18 years) and late onset (age ≥18 years) – as a unifying diagnostic term encompassing both entities.</p></div><div id="hdls.Prevalence"><h3>Prevalence</h3><p>Based on a few screening studies in cohorts with leukoencephalopathies/leukodystrophies, the total worldwide prevalence of <i>CSF1R</i>-related disorder to date is estimated to be 0.5-1.5:100,000 [<a class="bibr" href="#hdls.REF.papapetropoulos.2022.788168" rid="hdls.REF.papapetropoulos.2022.788168">Papapetropoulos et al 2022</a>].</p></div></div><div id="hdls.Genetically_Related_Allelic_Disorde"><h2 id="_hdls_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CSF1R</i>.</p></div><div id="hdls.Differential_Diagnosis"><h2 id="_hdls_Differential_Diagnosis_">Differential Diagnosis</h2><p><i>CSF1R</i>-related disorder may present with a range of non-motor and motor features, which may be nonspecific and overlap with other neurodegenerative genetic disorders and conditions that are often of unknown cause (e.g., multiple sclerosis and atypical parkinsonism, including corticobasal degeneration, multiple system atrophy, progressive supranuclear palsy, and frontotemporal lobal degeneration [<a class="bibr" href="#hdls.REF.baba.2006.300" rid="hdls.REF.baba.2006.300">Baba et al 2006</a>, <a class="bibr" href="#hdls.REF.sundal.2013.869" rid="hdls.REF.sundal.2013.869">Sundal et al 2013</a>]). At present, there are several other clinical, radiologic, and pathologic mimics of <i>CSF1R</i>-related disorder, including those described below and in <a href="/books/NBK100239/table/hdls.T.genetic_disorders_to_consider_in/?report=objectonly" target="object" rid-ob="figobhdlsTgeneticdisorderstoconsiderin">Table 3</a>.</p><div id="hdls.EarlyOnset_CSF1RRelated_Disorder"><h3>Early-Onset <i>CSF1R</i>-Related Disorder</h3><p>Hereditary disorders that primarily affect the central nervous system and manifest with glial and/or myelin abnormalities may mimic early-onset <i>CSF1R</i>-related disorder (see <a href="/books/NBK100239/table/hdls.T.genetic_disorders_to_consider_in/?report=objectonly" target="object" rid-ob="figobhdlsTgeneticdisorderstoconsiderin">Table 3</a>) [<a class="bibr" href="#hdls.REF.sarret.2020.10" rid="hdls.REF.sarret.2020.10">Sarret 2020</a>, <a class="bibr" href="#hdls.REF.davies.2023.401" rid="hdls.REF.davies.2023.401">Davies et al 2023</a>, <a class="bibr" href="#hdls.REF.ja_czewska.2023.269" rid="hdls.REF.ja_czewska.2023.269">Jańczewska et al 2023</a>].</p></div><div id="hdls.LateOnset_CSF1RRelated_Disorder"><h3>Late-Onset <i>CSF1R</i>-Related Disorder</h3><p><b>Primary progressive multiple sclerosis.</b> Before the discovery of the molecular genetic cause of the disorder, <i>CSF1R</i>-related disorder was frequently misdiagnosed as multiple sclerosis, particularly primary progressive multiple sclerosis (PPMS). There is significant clinical overlap between PPMS (average age of onset: 32 years) and late-onset <i>CSF1R</i>-related disorder [<a class="bibr" href="#hdls.REF.tutuncu.2013.188" rid="hdls.REF.tutuncu.2013.188">Tutuncu et al 2013</a>, <a class="bibr" href="#hdls.REF.aharony.2017.61" rid="hdls.REF.aharony.2017.61">Aharony et al 2017</a>, <a class="bibr" href="#hdls.REF.saitoh.2019.22" rid="hdls.REF.saitoh.2019.22">Saitoh et al 2019</a>]. White matter lesions are seen in both PPMS and <i>CSF1R</i>-related disorder; however, confluent white matter lesions in frontoparietal areas are more consistent with <i>CSF1R</i>-related disorder than with PPMS [<a class="bibr" href="#hdls.REF.sundal.2015.328" rid="hdls.REF.sundal.2015.328">Sundal et al 2015</a>]. PPMS is also associated with callosomarginal lesions and later onset of cognitive decline than <i>CSF1R</i>-related disorder. Incontinence appears later in the disease course and correlates with the overall disability in PPMS [<a class="bibr" href="#hdls.REF.aharony.2017.61" rid="hdls.REF.aharony.2017.61">Aharony et al 2017</a>]. In contrast to <i>CSF1R</i>-related disorder, oligoclonal bands are often present in PPMS and can be used as a discriminative marker [<a class="bibr" href="#hdls.REF.saitoh.2019.22" rid="hdls.REF.saitoh.2019.22">Saitoh et al 2019</a>].</p><p><b>Genetic disorders.</b>
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<i>CSF1R</i>-related disorder may also phenotypically mimic genetic motor neuron disease and other neurodegenerative disorders featuring spasticity, parkinsonism, ataxia, and cognitive decline [<a class="bibr" href="#hdls.REF.baba.2006.300" rid="hdls.REF.baba.2006.300">Baba et al 2006</a>, <a class="bibr" href="#hdls.REF.aharony.2017.61" rid="hdls.REF.aharony.2017.61">Aharony et al 2017</a>, <a class="bibr" href="#hdls.REF.souza.2020.219" rid="hdls.REF.souza.2020.219">Souza et al 2020</a>]. These disorders can be distinguished by brain MRI findings characterized mainly by cerebral atrophy without the characteristic white matter lesions found in <i>CSF1R</i>-related disorder. However, molecular genetic testing or neuropathologic examination are needed to make the ultimate distinction.</p><ul><li class="half_rhythm"><div><i>AARS1</i>-related leukoencephalopathy or Swedish hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult-onset autosomal dominant progressive neurodegenerative disorder that clinically and pathologically mimics the late-onset form of <i>CSF1R</i>-related disorder [<a class="bibr" href="#hdls.REF.sundal.2019.188" rid="hdls.REF.sundal.2019.188">Sundal et al 2019</a>]. However, affected individuals show a unique neuroimaging pattern, with a centrifugally expanding rim of decreased diffusion evidenced by MRI diffusion-weighted/tensor imaging through the white matter around anterior ventricular horns [<a class="bibr" href="#hdls.REF.sundal.2014.444" rid="hdls.REF.sundal.2014.444">Sundal et al 2014</a>, <a class="bibr" href="#hdls.REF.sundal.2019.188" rid="hdls.REF.sundal.2019.188">Sundal et al 2019</a>].</div></li><li class="half_rhythm"><div><i>AARS2</i>-related leukoencephalopathy is an autosomal recessive progressive neurodegenerative disease with cognitive decline, neurobehavioral/psychiatric manifestations, cerebellar ataxia, and pyramidal and extrapyramidal features. In addition, most affected women develop premature ovarian insufficiency. The age of onset usually occurs between the second and fifth decades of life. Compared to <i>CSF1R</i>-related disorder, <i>AARS2</i>-related leukoencephalopathy has less corpus callosum involvement and usually no brain calcifications [<a class="bibr" href="#hdls.REF.papapetropoulos.2022.788168" rid="hdls.REF.papapetropoulos.2022.788168">Papapetropoulos et al 2022</a>, <a class="bibr" href="#hdls.REF.muthusamy.2023.1219324" rid="hdls.REF.muthusamy.2023.1219324">Muthusamy et al 2023</a>]. (See <a href="/books/n/gene/aars2-dis/?report=reader"><i>AARS2</i>-Related Disorder</a>.)</div></li><li class="half_rhythm"><div>A <i>CSF1R</i>-related disorder mimic with an autosomal dominant pattern of inheritance of unknown genetic cause was reported in a single family with typical clinical, radiologic, and neuropathologic features of late-onset <i>CSF1R</i>-related disorder, but without pathogenic variants in <i>CSF1R, AARS1</i>, <i>AARS2</i>, or other genes known to be associated with neurodegenerative disorders [<a class="bibr" href="#hdls.REF.dulski.2023b.307" rid="hdls.REF.dulski.2023b.307">Dulski et al 2023b</a>].</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTgeneticdisorderstoconsiderin"><a href="/books/NBK100239/table/hdls.T.genetic_disorders_to_consider_in/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobhdlsTgeneticdisorderstoconsiderin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.genetic_disorders_to_consider_in"><a href="/books/NBK100239/table/hdls.T.genetic_disorders_to_consider_in/?report=objectonly" target="object" rid-ob="figobhdlsTgeneticdisorderstoconsiderin">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genetic Disorders to Consider in the Differential Diagnosis of <i>CSF1R</i>-Related Disorder </p></div></div></div></div><div id="hdls.Management"><h2 id="_hdls_Management_">Management</h2><p>No clinical practice guidelines for <i>CSF1R</i>-related disorder have been published. Therefore, the following considerations are based on the authors' experience managing individuals with this disorder and should be viewed as personal opinions rather than recommendations.</p><p>Note that the care of individuals with early-onset <i>CSF1R</i>-related disorder requires addressing issues of developmental delay and skeletal abnormalities that are typically addressed by developmental pediatricians and pediatricians and thus are not discussed further in this chapter. Rather, the assessment and management of the manifestations of neurodegeneration observed in all individuals with <i>CSF1R</i>-related disorder are discussed in detail.</p><div id="hdls.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>CSF1R</i>-related disorder, the evaluations summarized in <a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTcsf1rrelateddisorderrecommended"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.csf1rrelated_disorder_recommended"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>CSF1R</i>-Related Disorder: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="hdls.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>The limited data available to date suggest that hematopoietic stem cell transplantation (HSCT) could modify disease progression in symptomatic individuals with early neurologic findings of <i>CSF1R</i>-related disorder [<a class="bibr" href="#hdls.REF.tipton.2021.2901" rid="hdls.REF.tipton.2021.2901">Tipton et al 2021</a>, <a class="bibr" href="#hdls.REF.dulski.2022a.2778" rid="hdls.REF.dulski.2022a.2778">Dulski et al 2022a</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>] and could be more beneficial in individuals with motor involvement (i.e., gait problems) as the initial and predominant disease manifestation, in contrast to individuals initially experiencing non-motor manifestations (i.e., cognitive impairment) [<a class="bibr" href="#hdls.REF.dulski.2022a.2778" rid="hdls.REF.dulski.2022a.2778">Dulski et al 2022a</a>]. However, before conclusions can be drawn about the role of HSCT in the treatment of individuals with <i>CSF1R</i>-related disorder, more data are needed.</p><p>Supportive treatment is recommended to improve quality of life, maximize function, and reduce complications. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_symptomatic/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisordersymptomatic">Table 5</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTcsf1rrelateddisordersymptomatic"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_symptomatic/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobhdlsTcsf1rrelateddisordersymptomatic"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.csf1rrelated_disorder_symptomatic"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_symptomatic/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisordersymptomatic">Table 5. </a></h4><p class="float-caption no_bottom_margin"><i>CSF1R-</i>Related Disorder: Symptomatic Treatment of Manifestations </p></div></div></div><div id="hdls.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended_1/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended1">Table 6</a> are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsTcsf1rrelateddisorderrecommended1"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended_1/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.T.csf1rrelated_disorder_recommended_1"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended_1/?report=objectonly" target="object" rid-ob="figobhdlsTcsf1rrelateddisorderrecommended1">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>CSF1R-</i>Related Disorder: Recommended Surveillance </p></div></div></div><div id="hdls.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>As many individuals with <i>CSF1R</i>-related disorder have gait problems and cognitive decline, sedatives, antipsychotics, and other medications that may decrease alertness and increase the risk of falling should be used cautiously.</p></div><div id="hdls.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#hdls.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="hdls.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>In a retrospective cohort study, it was observed that glucocorticoids might protect against symptomatic disease onset in individuals at risk for late-onset <i>CSF1R-</i>related disorder (i.e., asymptomatic individuals with a heterozygous <i>CSF1R</i> pathogenic variant) [<a class="bibr" href="#hdls.REF.dulski.2023a.1545" rid="hdls.REF.dulski.2023a.1545">Dulski et al 2023a</a>]. This effect was also observed in a mouse model of the disease [<a class="bibr" href="#hdls.REF.chitu.2023.2664" rid="hdls.REF.chitu.2023.2664">Chitu et al 2023</a>]. For a detailed discussion on the optimal dose, route of administration, type of glucocorticoid, and timing of therapy, see <a class="bibr" href="#hdls.REF.dulski.2023d.444" rid="hdls.REF.dulski.2023d.444">Dulski et al [2023d]</a>. Note that glucocorticoids are not beneficial in individuals with advanced disease [<a class="bibr" href="#hdls.REF.dulski.2023d.444" rid="hdls.REF.dulski.2023d.444">Dulski et al 2023d</a>].</p><p>Currently, one interventional clinical trial is in progress, enrolling individuals age 18 years and older with the late-onset <i>CSF1R</i>-related disorder commonly known as adult-onset leukoencephalopathy w/axonal spheroids & pigmented glia (ALSP) (<a href="https://clinicaltrials.gov/study/NCT05677659" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT05677659</a>). It is a Phase II multicenter, open-label study investigating the safety and tolerability of VGL101 (Vigil Neuroscience, Inc), a humanized monoclonal antibody acting as an agonist for the triggering receptor expressed on myeloid cells 2 (TREM2) receptor. Since TREM2 and macrophage colony-stimulating factor 1 receptor (CSF1R; encoded by <i>CSF1R</i>) share common signaling pathways, it is hypothesized that activation of TREM2 may compensate for deficiency in CSF1R.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="hdls.Genetic_Counseling"><h2 id="_hdls_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="hdls.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Early-onset <i>CSF1R</i>-related disorder is typically caused by biallelic pathogenic variants and inherited in an autosomal recessive manner. Rarely, early-onset <i>CSF1R</i>-related disorder may be caused by a heterozygous pathogenic variant [<a class="bibr" href="#hdls.REF.breningstall.2020.44" rid="hdls.REF.breningstall.2020.44">Breningstall & Asis 2020</a>; <a class="bibr" href="#hdls.REF.sriram.2022.311" rid="hdls.REF.sriram.2022.311">Sriram et al 2022</a>; <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>; J Dulski, unpublished data].</p><p>Late-onset <i>CSF1R</i>-related disorder is typically caused by a heterozygous pathogenic variant and inherited in an autosomal dominant manner. Rarely, late-onset <i>CSF1R</i>-related disorder may be caused by biallelic <i>CSF1R</i> pathogenic variants [<a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>; <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>; J Dulski, unpublished data].</p><p>Note: While biallelic pathogenic variants are typically associated with early-onset disease and heterozygous pathogenic variants are typically associated with late-onset disease, definitive prediction of phenotype based on <i>CSF1R</i> genotype is not possible at this time [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</p></div><div id="hdls.Autosomal_Recessive_Inheritance__Ri"><h3>Autosomal Recessive Inheritance – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an individual with <i>CSF1R</i>-related disorder caused by biallelic <i>CSF1R</i> pathogenic variants are presumed to be heterozygous for a <i>CSF1R</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a <i>CSF1R</i> pathogenic variant and to allow reliable recurrence risk assessment.</div></li><li class="half_rhythm"><div>If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>The heterozygous parents of an individual with early-onset <i>CSF1R</i>-related disorder caused by biallelic pathogenic variants are typically asymptomatic; however, definitive prediction of phenotype based on <i>CSF1R</i> genotype is not possible at this time [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>CSF1R</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial <i>CSF1R</i> pathogenic variants.</div></li><li class="half_rhythm"><div>Sibs who inherit the same biallelic <i>CSF1R</i> pathogenic variants do not necessarily have the same clinical manifestations early in the disease course; however, in the end stage, all individuals with <i>CSF1R</i>-related disorder typically have devastating neurologic involvement.</div></li><li class="half_rhythm"><div>The heterozygous sibs of an individual with <i>CSF1R</i>-related disorder caused by biallelic pathogenic variants are typically asymptomatic; however, definitive prediction of phenotype based on <i>CSF1R</i> genotype is not possible at this time [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with biallelic <i>CSF1R</i> pathogenic variants are obligate heterozygotes for a pathogenic variant in <i>CSF1R</i>.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being heterozygous for a <i>CSF1R</i> pathogenic variant.</p><p><b>Heterozygote detection.</b> Heterozygote testing for at-risk relatives requires prior identification of the <i>CSF1R</i> pathogenic variants in the family.</p></div><div id="hdls.Autosomal_Dominant_Inheritance__Ris"><h3>Autosomal Dominant Inheritance – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>Many individuals with <i>CSF1R-</i>related disorder caused by a heterozygous <i>CSF1R</i> pathogenic variant have an affected parent [<a class="bibr" href="#hdls.REF.rademakers.2011.200" rid="hdls.REF.rademakers.2011.200">Rademakers et al 2011</a>, <a class="bibr" href="#hdls.REF.kinoshita.2012.115" rid="hdls.REF.kinoshita.2012.115">Kinoshita et al 2012</a>, <a class="bibr" href="#hdls.REF.stabile.2016.1565" rid="hdls.REF.stabile.2016.1565">Stabile et al 2016</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</div></li><li class="half_rhythm"><div>Some individuals with <i>CSF1R</i>-related disorder caused by a heterozygous <i>CSF1R</i> pathogenic variant represent a simplex case (i.e., the only family member known to be affected). Such individuals may have the disorder as the result of:</div><ul><li class="half_rhythm"><div>A pathogenic variant that occurred <i>de novo</i> in the proband;</div></li><li class="half_rhythm"><div>A pathogenic variant inherited from a mosaic parent; or</div></li><li class="half_rhythm"><div>A pathogenic variant inherited from an asymptomatic heterozygous parent. (The penetrance of <i>CSF1R</i>-related disorder is estimated to be high but not complete [<a class="bibr" href="#hdls.REF.karle.2013.2039" rid="hdls.REF.karle.2013.2039">Karle et al 2013</a>, <a class="bibr" href="#hdls.REF.sundal.2015.328" rid="hdls.REF.sundal.2015.328">Sundal et al 2015</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>].)</div></li></ul></li><li class="half_rhythm"><div>If the proband appears to be the only affected family member, molecular genetic testing is recommended for the parents of the proband to evaluate their genetic status, inform recurrence risk assessment, and provide insight into familial genotype-phenotype correlations.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div class="half_rhythm">The proband has a <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div class="half_rhythm">The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism.* Somatic and germline mosaicism has been reported in an unaffected mother of four sibs with late-onset <i>CSF1R</i>-related disorder [<a class="bibr" href="#hdls.REF.eichler.2016.1666" rid="hdls.REF.eichler.2016.1666">Eichler et al 2016</a>]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.</div><div class="half_rhythm">* Note: If the parent is the individual in whom the pathogenic variant first occurred, the parent may have somatic mosaicism for the variant and may be mildly/minimally affected.</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with <i>CSF1R</i>-related disorder may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, late onset of the disease in the affected parent, or reduced penetrance [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>]. Therefore, a negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent has the pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is known to be heterozygous for the <i>CSF1R</i> pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.</div><ul><li class="half_rhythm"><div>Sibs who are heterozygous for the same <i>CSF1R</i> pathogenic variant do not necessarily have the same clinical manifestations early in the disease course; however, in the end stage, all individuals with <i>CSF1R</i>-related disorder typically have devastating neurologic involvement.</div></li><li class="half_rhythm"><div>On average, women develop the first manifestations of late-onset <i>CSF1R</i>-related disorder earlier (age 40 years) than men (age 47 years).</div></li></ul></li><li class="half_rhythm"><div>If the <i>CSF1R</i> pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism [<a class="bibr" href="#hdls.REF.eichler.2016.1666" rid="hdls.REF.eichler.2016.1666">Eichler et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>CSF1R</i> pathogenic variant but are clinically unaffected, sibs are still presumed to be at increased risk for <i>CSF1R</i>-related disorder because of possible reduced penetrance in a parent and the possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with a heterozygous <i>CSF1R</i> pathogenic variant has a 50% chance of inheriting the pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the <i>CSF1R</i> pathogenic variant, the parent's family members may be at risk.</p></div><div id="hdls.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Predictive testing (i.e., testing of asymptomatic at-risk individuals)</b>
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</p><ul><li class="half_rhythm"><div>Predictive testing for at-risk relatives is possible once the causative <i>CSF1R</i> pathogenic variant(s) have been identified in an affected family member. Such testing is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals.</div></li><li class="half_rhythm"><div>Potential consequences of such testing (including, but not limited to, socioeconomic changes and the need for long-term follow up and evaluation arrangements for individuals with a positive test result) as well as the capabilities and limitations of predictive testing should be discussed in the context of formal genetic counseling prior to testing.</div></li></ul><p>
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<b>Predictive testing in minors (i.e., testing of asymptomatic at-risk individuals age <18 years)</b>
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</p><ul><li class="half_rhythm"><div>Predictive testing of minors for adult-onset disorders for which no treatment exists is not considered appropriate. Such testing negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.</div></li><li class="half_rhythm"><div>For more information, see the National Society of Genetic Counselors <a href="https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for-adult-onset-conditions" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">position statement</a> on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics <a href="https://pediatrics.aappublications.org/content/131/3/620.full.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">policy statement</a>: ethical and policy issues in genetic testing and screening of children.</div></li></ul><p>In a family with an established diagnosis of <i>CSF1R</i>-related disorder, it is appropriate to consider testing symptomatic individuals regardless of age.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul></div><div id="hdls.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>CSF1R</i> pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing for <i>CSF1R</i>-related disorder are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider decisions regarding prenatal and preimplantation genetic testing to be the choice of the parents, discussion of these issues is appropriate.</p></div></div><div id="hdls.Resources"><h2 id="_hdls_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>Sisters’ Hope Foundation</b>
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</div><div><b>Email:</b> info@sistershopefoundation.org</div><div>
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<a href="https://sistershopefoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">sistershopefoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Alex, The Leukodystrophy Charity</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 020 7701 4388</div><div><b>Email:</b> info@alextlc.org</div><div>
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<a href="https://alextlc.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">alextlc.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>European Leukodystrophy Association (ELA)</b>
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</div><div>
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<a href="http://www.ela-asso.com" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ela-asso.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>Leukodystrophy Australia</b>
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</div><div>Australia</div><div><b>Phone:</b> 1800 141 400</div><div><b>Email:</b> info@leuko.org.au</div><div>
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<a href="https://www.leuko.org.au/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">leuko.org.au</a>
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</div></li><li class="half_rhythm"><div>
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<b>United Leukodystrophy Foundation</b>
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</div><div><b>Phone:</b> 815-748-0844</div><div><b>Email:</b> office@ulf.org</div><div>
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<a href="https://ulf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ulf.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Myelin Disorders Bioregistry Project</b>
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</div><div><b>Phone:</b> 215-590-1719</div><div><b>Email:</b> sherbinio@chop.edu</div><div>
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<a href="https://www.chop.edu/research/myelin-disorders-biorepository-project" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Myelin Disorders Bioregistry Project</a>
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</div></li></ul>
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</div><div id="hdls.Molecular_Genetics"><h2 id="_hdls_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsmolgenTA"><a href="/books/NBK100239/table/hdls.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobhdlsmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.molgen.TA"><a href="/books/NBK100239/table/hdls.molgen.TA/?report=objectonly" target="object" rid-ob="figobhdlsmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">CSF1R-Related Disorder: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighdlsmolgenTB"><a href="/books/NBK100239/table/hdls.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobhdlsmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hdls.molgen.TB"><a href="/books/NBK100239/table/hdls.molgen.TB/?report=objectonly" target="object" rid-ob="figobhdlsmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for CSF1R-Related Disorder (View All in OMIM) </p></div></div><div id="hdls.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CSF1R</i> encodes macrophage colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor primarily for cytokine colony-stimulating factor 1 (CSF-1) that regulates the survival, proliferation, differentiation, and function of mononuclear phagocytic cells, including microglia of the central nervous system . CSF1R comprises a highly glycosylated extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. Binding of CSF-1 to its receptor, CSF1R, results in the formation of receptor homodimers and subsequent autophosphorylation of several important proteins, including the phosphatase SHP-1 and the kinases Src, PLC-γ, PI(3)K, Akt, and Erk [<a class="bibr" href="#hdls.REF.rademakers.2011.200" rid="hdls.REF.rademakers.2011.200">Rademakers et al 2011</a>]. In the brain, CSF1R is predominately expressed in microglial cells [<a class="bibr" href="#hdls.REF.papapetropoulos.2022.788168" rid="hdls.REF.papapetropoulos.2022.788168">Papapetropoulos et al 2022</a>].</p><p>To date, most reported <i>CSF1R</i> pathogenic variants that cause <i>CSF1R</i>-related disorder affect kinase activity and potentially phosphorylation of downstream targets. However, the mechanisms of neuronal/glial dysfunction underlying <i>CSF1R</i>-related disorder remain to be fully elucidated [<a class="bibr" href="#hdls.REF.papapetropoulos.2022.788168" rid="hdls.REF.papapetropoulos.2022.788168">Papapetropoulos et al 2022</a>].</p><p><b>Mechanism of disease causation.</b> The mechanisms of disease causation are not fully understood and likely differ depending on the <i>CSF1R</i> pathogenic variant(s) and possible interplay with other genetic and non-genetic factors [<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al 2024</a>].</p><p><b><i>CSF1R</i>-specific laboratory technical considerations.</b> While most pathogenic variants underlying <i>CSF1R</i>-related disorder are within coding or canonical splice site regions, several splicing variants beyond the canonical splice site have been identified that may be detected by genome sequencing [<a class="bibr" href="#hdls.REF.rademakers.2011.200" rid="hdls.REF.rademakers.2011.200">Rademakers et al 2011</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.wu.2022.3265" rid="hdls.REF.wu.2022.3265">Wu et al 2022</a>].</p></div></div><div id="hdls.Chapter_Notes"><h2 id="_hdls_Chapter_Notes_">Chapter Notes</h2><div id="hdls.Author_Notes"><h3>Author Notes</h3><p>Dr Wszolek (<a href="mailto:dev@null" data-email="ude.oyam@weingibz.kelozsw" class="oemail">ude.oyam@weingibz.kelozsw</a>) and Dr Dulski (<a href="mailto:dev@null" data-email="ude.oyam@walsoraj.ikslud" class="oemail">ude.oyam@walsoraj.ikslud</a>; <a href="mailto:dev@null" data-email="lp.ude.demug@ikslud.walsoraj" class="oemail">lp.ude.demug@ikslud.walsoraj</a>) are actively involved in clinical research regarding individuals with <i>CSF1R</i>-related disorder. They would be happy to communicate with patients and their families, patient organizations, and clinicians treating patients with the disorder.</p><p>Contact Drs Wszolek and Dulski to inquire about review of <i>CSF1R</i> variants of uncertain significance.</p></div><div id="hdls.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the patients, their families, and the Sisters' Hope and My Complex Genes Foundations for their never-ending support, encouragement, and inspiration.</p><p>Jaroslaw Dulski is partially supported by the Haworth Family Professorship in Neurodegenerative Diseases fund (90052067). He serves as an editorial board member of <i>Neurologia i Neurochirurgia Polska</i>. He received speakers' bureau honoraria from VM Media Ltd, Radosław Lipiński 90 Consulting, Ipsen. He has intellectual property rights for "Application of Hydrogen Peroxide and 17β-Estradiol and its Metabolites as Biomarkers in a Method of Diagnosing Neurodegenerative Diseases In Vitro" (WO/2023/234790).</p><p>Zbigniew K Wszolek is partially supported by the NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, the gifts from the Donald G and Jodi P Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, the Albertson Parkinson's Research Foundation, and the PPND Family Foundation. He serves as PI or co-PI on Biohaven Pharmaceuticals, Inc (BHV4157-206) and Vigil Neuroscience, Inc (VGL101-01.002, VGL101-01.201, PET tracer development protocol, Csf1r biomarker and repository project, and ultra-high field MRI in the diagnosis and management of CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia) projects/grants. He serves as co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for the Vigil Neuroscience, Inc, and as a consultant on neurodegenerative medical research for Eli Lilli & Company.</p></div><div id="hdls.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>4 April 2024 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 October 2017 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>18 December 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 August 2012 (me) Review posted live</div></li><li class="half_rhythm"><div>23 May 2012 (zkw) Original submission</div></li></ul></div></div><div id="hdls.References"><h2 id="_hdls_References_">References</h2><div id="hdls.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.aharony.2017.61">Aharony
|
|
SM, Lam
|
|
O, Corcos
|
|
J. Evaluation of lower urinary tract symptoms in multiple sclerosis patients: review of the literature and current guidelines.
|
|
Can Urol Assoc J.
|
|
2017;11:61-4.
|
|
[<a href="/pmc/articles/PMC5403674/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5403674</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28443147" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28443147</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.ahmed.2013.483">Ahmed
|
|
A, Simmons
|
|
Z.
|
|
Pseudobulbar affect: prevalence and management.
|
|
Ther Clin Risk Manag.
|
|
2013;9:483-9.
|
|
[<a href="/pmc/articles/PMC3849173/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3849173</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24348042" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24348042</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.baba.2006.300">Baba
|
|
Y, Ghetti
|
|
B, Baker
|
|
MC, Uitti
|
|
RJ, Hutton
|
|
ML, Yamaguchi
|
|
K, Bird
|
|
T, Lin
|
|
W, DeLucia
|
|
MW, Dickson
|
|
DW, Wszolek
|
|
ZK. Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.
|
|
Acta Neuropathol.
|
|
2006;111:300-11.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16523341" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16523341</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.bender.2014.2351">Bender
|
|
B, Klose
|
|
U, Lindig
|
|
T, Biskup
|
|
S, Nägele
|
|
T, Schöls
|
|
L, Karle
|
|
KN. Imaging features in conventional MRI, spectroscopy and diffusion weighted images of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS).
|
|
J Neurol.
|
|
2014;261:2351-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25239393" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25239393</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.breningstall.2020.44">Breningstall
|
|
GN, Asis
|
|
M. Bone disease associated with hereditary diffuse leukoencephalopathy with spheroids.
|
|
Pediatr Neurol.
|
|
2020;112:44-6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32911262" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32911262</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.chitu.2023.2664">Chitu
|
|
V, Biundo
|
|
F, Oppong-Asare
|
|
J, Gökhan
|
|
Ş, Aguilan
|
|
JT, Dulski
|
|
J, Wszolek
|
|
ZK, Sidoli
|
|
S, Stanley
|
|
ER. Prophylactic effect of chronic immunosuppression in a mouse model of CSF-1 receptor-related leukoencephalopathy.
|
|
Glia.
|
|
2023;71:2664-78.
|
|
[<a href="/pmc/articles/PMC10529087/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10529087</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37519044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37519044</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.daida.2017.2507">Daida
|
|
K, Nishioka
|
|
K, Li
|
|
Y, Nakajima
|
|
S, Tanaka
|
|
R, Hattori
|
|
N.
|
|
CSF1R mutation p.G589R and the distribution pattern of brain calcification.
|
|
Intern Med.
|
|
2017;56:2507-12.
|
|
[<a href="/pmc/articles/PMC5643183/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5643183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28824062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28824062</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.davies.2023.401">Davies
|
|
A, Tolliday
|
|
A, Craven
|
|
I, Connolly
|
|
DJA. An approach to reporting paediatric leukoencephalopathy and leukodystrophies.
|
|
Clin Radiol.
|
|
2023;78:401-11.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/36990927" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36990927</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2023a.1545">Dulski
|
|
J, Heckman
|
|
MG, Nowak
|
|
JM, Wszolek
|
|
ZK. Protective effect of glucocorticoids against symptomatic disease in CSF1R variant carriers.
|
|
Mov Disord.
|
|
2023a;38:1545-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/37309919" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37309919</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2022a.2778">Dulski
|
|
J, Heckman
|
|
MG, White
|
|
LJ, Żur-Wyrozumska
|
|
K, Lund
|
|
TC, Wszolek
|
|
ZK. Hematopoietic stem cell transplantation in CSF1R-related leukoencephalopathy: retrospective study on predictors of outcomes.
|
|
Pharmaceutics.
|
|
2022a;14:2778.
|
|
[<a href="/pmc/articles/PMC9788080/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9788080</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36559271" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36559271</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2023b.307">Dulski
|
|
J, Koga
|
|
S, Dickson
|
|
DW, Wszolek
|
|
ZK. Report of a family with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) without mutations in CSF1R, AARS1 or AARS2.
|
|
Mov Disord Clin Pract.
|
|
2023b;10:307-12.
|
|
[<a href="/pmc/articles/PMC9941916/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9941916</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36825047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36825047</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2022b.1110">Dulski
|
|
J, Middlebrooks
|
|
EH, Wszolek
|
|
ZK. Novel application of 7T MRI in CSF1R-related leukoencephalopathy.
|
|
Neurology.
|
|
2022b;99:1110-1111.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/36180242" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36180242</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2024.105894">Dulski
|
|
J, Muthusamy
|
|
K, Lund
|
|
T, Wszolek
|
|
Z.
|
|
CSF1R-related disorder: state of the art, challenges, and proposition of a new terminology.
|
|
Parkinsonism Relat Disord.
|
|
2024;121:105894.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/37839910" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37839910</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2023c.160">Dulski
|
|
J, Souza
|
|
J, Santos
|
|
ML, Wszolek
|
|
ZK. Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.
|
|
Orphanet J Rare Dis.
|
|
2023c;18:160.
|
|
[<a href="/pmc/articles/PMC10288773/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10288773</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37349768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37349768</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.dulski.2023d.444">Dulski
|
|
J, Stanley
|
|
ER, Chitu
|
|
V, Wszolek
|
|
ZK. Potential use of glucocorticosteroids in CSF1R mutation carriers - current evidence and future directions.
|
|
Neurol Neurochir Pol.
|
|
2023d;57:444-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/37889001" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37889001</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.eichler.2016.1666">Eichler
|
|
FS, Li
|
|
J, Guo
|
|
Y, Caruso
|
|
PA, Bjonnes
|
|
AC, Pan
|
|
J, Booker
|
|
JK, Lane
|
|
JM, Tare
|
|
A, Vlasac
|
|
I, Hakonarson
|
|
H, Gusella
|
|
JF, Zhang
|
|
J, Keating
|
|
BJ, Saxena
|
|
R. CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.
|
|
Brain.
|
|
2016;139:1666-72.
|
|
[<a href="/pmc/articles/PMC4892751/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4892751</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27190017" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27190017</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.guo.2019.925">Guo
|
|
L, Bertola
|
|
DR, Takanohashi
|
|
A, Saito
|
|
A, Segawa
|
|
Y, Yokota
|
|
T, Ishibashi
|
|
S, Nishida
|
|
Y, Yamamoto
|
|
GL, Franco
|
|
J, Honjo
|
|
RS, Kim
|
|
CA, Musso
|
|
CM, Timmons
|
|
M, Pizzino
|
|
A, Taft
|
|
RJ, Lajoie
|
|
B, Knight
|
|
MA, Fischbeck
|
|
KH, Singleton
|
|
AB, Ferreira
|
|
CR, Wang
|
|
Z, Yan
|
|
L, Garbern
|
|
JY, Simsek-Kiper
|
|
PO, Ohashi
|
|
H, Robey
|
|
PG, Boyde
|
|
A, Matsumoto
|
|
N, Miyake
|
|
N, Spranger
|
|
J, Schiffmann
|
|
R, Vanderver
|
|
A, Nishimura
|
|
G, Passos-Bueno
|
|
M, Simons
|
|
C, Ishikawa
|
|
K, Ikegawa
|
|
S. Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-pyle disease spectrum and degenerative encephalopathy with brain malformation.
|
|
Am J Hum Genet.
|
|
2019;104:925-35.
|
|
[<a href="/pmc/articles/PMC6507048/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6507048</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30982609" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30982609</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.ishiguro.2023.1861">Ishiguro
|
|
T, Konno
|
|
T, Hara
|
|
N, Zhu
|
|
B, Okada
|
|
S, Shibata
|
|
M, Saika
|
|
R, Kitano
|
|
T, Toko
|
|
M, Nezu
|
|
T, Hama
|
|
Y, Kawazoe
|
|
T, Takahashi-Iwata
|
|
I, Yabe
|
|
I, Sato
|
|
K, Takeda
|
|
H, Toda
|
|
S, Nishimiya
|
|
J, Teduka
|
|
T, Nozaki
|
|
H, Kasuga
|
|
K, Miyashita
|
|
A, Onodera
|
|
O, Ikeuchi
|
|
T.
|
|
Novel partial deletions, frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy.
|
|
Eur J Neurol.
|
|
2023;30:1861-70.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/36943150" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36943150</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.ja_czewska.2023.269">Jańczewska
|
|
I, Preis-Orlikowska
|
|
J, Domżalska-Popadiuk
|
|
I, Preis
|
|
K, Jańczewska
|
|
A. Children with corpus callosum anomalies: clinical characteristics and developmental outcomes.
|
|
Neurol Neurochir Pol.
|
|
2023;57:269-81.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/37078131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37078131</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.jiang.2022.902067">Jiang
|
|
J, Li
|
|
W, Wang
|
|
X, Du
|
|
Z, Chen
|
|
J, Liu
|
|
Y, Li
|
|
W, Lu
|
|
Z, Wang
|
|
Y, Xu
|
|
J. Two novel intronic mutations in the CSF1R gene in two families with CSF1R-microglial encephalopathy.
|
|
Front Cell Dev Biol.
|
|
2022;10:902067.
|
|
[<a href="/pmc/articles/PMC9198639/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9198639</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35721475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35721475</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.kaler.2020.e6922">Kaler
|
|
J, Hussain
|
|
A, Patel
|
|
S, Majhi
|
|
S. Neuromuscular junction disorders and floppy infant syndrome: a comprehensive review.
|
|
Cureus.
|
|
2020;12:e6922.
|
|
[<a href="/pmc/articles/PMC7008760/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7008760</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32071826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32071826</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.karle.2013.2039">Karle
|
|
KN, Biskup
|
|
S, Schüle
|
|
R, Schweitzer
|
|
KJ, Krüger
|
|
R, Bauer
|
|
P, Bender
|
|
B, Nägele
|
|
T, Schöls
|
|
L. De novo mutations in hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS).
|
|
Neurology
|
|
2013;81:2039-44.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24198292" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24198292</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.k_nd__.2021.1888">Kındış
|
|
E, Simsek-Kiper
|
|
P, Koşukcu
|
|
C, Taşkıran
|
|
EZ, Göçmen
|
|
R, Utine
|
|
E, Haliloğlu
|
|
G, Boduroğlu
|
|
K, Alikaşifoğlu
|
|
M. Further expanding the mutational spectrum of brain abnormalities, neurodegeneration, and dysosteosclerosis: a rare disorder with neurologic regression and skeletal features.
|
|
Am J Med Genet Part A.
|
|
2021;185:1888–96.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/33749994" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33749994</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.kinoshita.2012.115">Kinoshita
|
|
M, Yoshida
|
|
K, Oyanagi
|
|
K, Hashimoto
|
|
T, Ikeda
|
|
S. Hereditary diffuse leukoencephalopathy with axonal spheroids caused by R782H mutation in CSF1R: case report.
|
|
J Neurol Sci.
|
|
2012;318:115–8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22503135" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22503135</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.konno.2014.139">Konno
|
|
T, Tada
|
|
M, Tada
|
|
M, Koyama
|
|
A, Nozaki
|
|
H, Harigaya
|
|
Y, Nishimiya
|
|
J, Matsunaga
|
|
A, Yoshikura
|
|
N, Ishihara
|
|
K, Arakawa
|
|
M, Isami
|
|
A, Okazaki
|
|
K, Yokoo
|
|
H, Itoh
|
|
K, Yoneda
|
|
M, Kawamura
|
|
M, Inuzuka
|
|
T, Takahashi
|
|
H, Nishizawa
|
|
M, Onodera
|
|
O, Kakita
|
|
A, Ikeuchi
|
|
T.
|
|
Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.
|
|
Neurology.
|
|
2014;82:139-48.
|
|
[<a href="/pmc/articles/PMC3937843/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3937843</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24336230" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24336230</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.konno.2017.37">Konno
|
|
T, Yoshida
|
|
K, Mizuno
|
|
T, Kawarai
|
|
T, Tada
|
|
M, Nozaki
|
|
H, Ikeda
|
|
SI, Nishizawa
|
|
M, Onodera
|
|
O, Wszolek
|
|
ZK, Ikeuchi
|
|
T. Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation.
|
|
Eur J Neurol.
|
|
2017;24:37-45.
|
|
[<a href="/pmc/articles/PMC5215554/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5215554</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27680516" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27680516</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.konno.2018.142">Konno
|
|
T, Yoshida
|
|
K, Mizuta
|
|
I, Mizuno
|
|
T, Kawarai
|
|
T, Tada
|
|
M, Nozaki
|
|
H, Ikeda
|
|
SI, Onodera
|
|
O, Wszolek
|
|
ZK, Ikeuchi
|
|
T. Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation.
|
|
Eur J Neurol.
|
|
2018;25:142-7.
|
|
[<a href="/pmc/articles/PMC5741468/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5741468</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28921817" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28921817</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.lee.2015.817">Lee
|
|
D, Yun
|
|
JY, Jeong
|
|
JH, Yoshida
|
|
K, Nagasaki
|
|
S, Ahn
|
|
TB. Clinical evolution, neuroimaging, and volumetric analysis of a patient with a CSF1R mutation who presented with progressive nonfluent aphasia.
|
|
Parkinsonism Relat Disord.
|
|
2015;21:817-20.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25934184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25934184</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.mccormick.2018.714">McCormick
|
|
EM, Zolkipli-Cunningham
|
|
Z, Falk
|
|
MJ. Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease.
|
|
Curr Opin Pediatr.
|
|
2018;30:714-24.
|
|
[<a href="/pmc/articles/PMC6467265/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6467265</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30199403" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30199403</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.mickeviciute.2022.269">Mickeviciute
|
|
GC, Valiuskyte
|
|
M, Plattén
|
|
M, Wszolek
|
|
ZK, Andersen
|
|
O, Danylaité Karrenbauer
|
|
V, Ineichen
|
|
BV, Granberg
|
|
T. Neuroimaging phenotypes of CSF1R-related leukoencephalopathy: Systematic review, meta-analysis, and imaging recommendations.
|
|
J Intern Med.
|
|
2022;291:269-82.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/34875121" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34875121</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.monies.2017.1144">Monies
|
|
D, Maddirevula
|
|
S, Kurdi
|
|
W, Alanazy
|
|
MH, Alkhalidi
|
|
H, Al-Owain
|
|
M, Sulaiman
|
|
RA, Faqeih
|
|
E, Goljan
|
|
E, Ibrahim
|
|
N, Abdulwahab
|
|
F, Hashem
|
|
M, Abouelhoda
|
|
M, Shaheen
|
|
R, Arold
|
|
ST, Alkuraya
|
|
FS. Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation.
|
|
Genet Med.
|
|
2017;19:1144–50.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28383543" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28383543</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.muthusamy.2023.1219324">Muthusamy
|
|
K, Sivadasan
|
|
A, Dixon
|
|
L, Sudhakar
|
|
S, Thomas
|
|
M, Danda
|
|
S, Wszolek
|
|
ZK, Wierenga
|
|
K, Dhamija
|
|
R, Gavrilova
|
|
R. Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions.
|
|
Front Neurol.
|
|
2023;14:1219324.
|
|
[<a href="/pmc/articles/PMC10410460/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10410460</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37564735" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37564735</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.oosterhof.2019.936">Oosterhof
|
|
N, Chang
|
|
IJ, Karimiani
|
|
EG, Kuil
|
|
LE, Jensen
|
|
DM, Daza
|
|
R, Young
|
|
E, Astle
|
|
L, van der Linde
|
|
HC, Shivaram
|
|
GM, Demmers
|
|
J, Latimer
|
|
CS, Keene
|
|
CD, Loter
|
|
E, Maroofian
|
|
R, van Ham
|
|
TJ, Hevner
|
|
RF, Bennett
|
|
JT. Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.
|
|
Am J Hum Genet.
|
|
2019;104:936-47.
|
|
[<a href="/pmc/articles/PMC6506793/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6506793</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30982608" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30982608</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.papapetropoulos.2022.788168">Papapetropoulos
|
|
S, Pontius
|
|
A, Finger
|
|
E, Karrenbauer
|
|
V, Lynch
|
|
DS, Brennan
|
|
M, Zappia
|
|
S, Koehler
|
|
W, Schoels
|
|
L, Hayer
|
|
SN, Konno
|
|
T, Ikeuchi
|
|
T, Lund
|
|
T, Orthmann-Murphy
|
|
J, Eichler
|
|
F, Wszolek
|
|
ZK. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: review of clinical manifestations as foundations for therapeutic development.
|
|
Front Neurol.
|
|
2022;12:788168.
|
|
[<a href="/pmc/articles/PMC8850408/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8850408</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35185751" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35185751</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.rademakers.2011.200">Rademakers
|
|
R, Baker
|
|
M, Nicholson
|
|
AM, Rutherford
|
|
NJ, Finch
|
|
N, Soto-Ortolaza
|
|
A, Lash
|
|
J, Wider
|
|
C, Wojtas
|
|
A, DeJesus-Hernandez
|
|
M, Adamson
|
|
J, Kouri
|
|
N, Sundal
|
|
C, Shuster
|
|
EA, Aasly
|
|
J, MacKenzie
|
|
J, Roeber
|
|
S, Kretzschmar
|
|
HA, Boeve
|
|
BF, Knopman
|
|
DS, Petersen
|
|
RC, Cairns
|
|
NJ, Ghetti
|
|
B, Spina
|
|
S, Garbern
|
|
J, Tselis
|
|
AC, Uitti
|
|
R, Das
|
|
P, Van Gerpen
|
|
JA, Meschia
|
|
JF, Levy
|
|
S, Broderick
|
|
DF, Graff-Radford
|
|
N, Ross
|
|
OA, Miller
|
|
BB, Swerdlow
|
|
RH, Dickson
|
|
DW, Wszolek
|
|
ZK. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.
|
|
Nat Genet.
|
|
2011;44:200-5.
|
|
[<a href="/pmc/articles/PMC3267847/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3267847</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22197934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22197934</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.richards.2015.405">Richards
|
|
S, Aziz
|
|
N, Bale
|
|
S, Bick
|
|
D, Das
|
|
S, Gastier-Foster
|
|
J, Grody
|
|
WW, Hegde
|
|
M, Lyon
|
|
E, Spector
|
|
E, Voelkerding
|
|
K, Rehm
|
|
HL, et al
|
|
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
|
Genet Med.
|
|
2015;17:405-24.
|
|
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.robinson.2015.42">Robinson
|
|
JL, Suh
|
|
E, Wood
|
|
EM, Lee
|
|
EB, Coslett
|
|
HB, Raible
|
|
K, Lee
|
|
VMY, Trojanowski
|
|
JQ, Van Deerlin
|
|
VM. Common neuropathological features underlie distinct clinical presentations in three siblings with hereditary diffuse leukoencephalopathy with spheroids caused by CSF1R p.Arg782His.
|
|
Acta Neuropathologica Communications.
|
|
2015;3:42.
|
|
[<a href="/pmc/articles/PMC4491242/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4491242</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26141825" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26141825</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.rosenstein.2022.599">Rosenstein
|
|
I, Andersen
|
|
O, Victor
|
|
D, Englund
|
|
E, Granberg
|
|
T, Hedberg-Oldfors
|
|
C, Jood
|
|
K, Fitrah
|
|
YA, Ikeuchi
|
|
T, Danylaité Karrenbauer
|
|
V. Four Swedish cases of CSF1R-related leukoencephalopathy: visualization of clinical phenotypes.
|
|
Acta Neurol Scand.
|
|
2022;145:599-609.
|
|
[<a href="/pmc/articles/PMC9304267/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9304267</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35119108" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35119108</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.rush.2023.1155387">Rush
|
|
BK, Tipton
|
|
PW, Strongosky
|
|
A, Wszolek
|
|
ZK. Neuropsychological profile of CSF1R-related leukoencephalopathy.
|
|
Front Neurol.
|
|
2023;14:1155387.
|
|
[<a href="/pmc/articles/PMC10272847/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10272847</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37333006" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37333006</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.saitoh.2019.22">Saitoh
|
|
BY, Yamasaki
|
|
R, Hiwatashi
|
|
A, Matsushita
|
|
T, Hayashi
|
|
S, Mitsunaga
|
|
Y, Maeda
|
|
Y, Isobe
|
|
N, Yoshida
|
|
K, Ikeda
|
|
SI, Kira
|
|
JI. Discriminative clinical and neuroimaging features of motor-predominant hereditary diffuse leukoencephalopathy with axonal spheroids and primary progressive multiple sclerosis: a preliminary cross-sectional study.
|
|
Mult Scler Relat Disord.
|
|
2019;31:22-31.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30901701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30901701</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sarret.2020.10">Sarret
|
|
C.
|
|
Leukodystrophies and genetic leukoencephalopathies in children.
|
|
Revue Neurologique.
|
|
2020;176:10-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/31174885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31174885</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.shu.2016.171">Shu
|
|
Y, Long
|
|
L, Liao
|
|
S, Yang
|
|
J, Li
|
|
J, Qiu
|
|
W, Yang
|
|
Y, Bao
|
|
J, Wu
|
|
A, Hu
|
|
X, Lu
|
|
Z. Involvement of the optic nerve in mutated CSF1R-induced hereditary diffuse leukoencephalopathy with axonal spheroids.
|
|
BMC Neurology.
|
|
2016;16:171.
|
|
[<a href="/pmc/articles/PMC5020510/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5020510</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27619214" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27619214</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.souza.2020.219">Souza
|
|
PVS, Badia
|
|
BML, Silva
|
|
LHL, Farias
|
|
IB, Pinto
|
|
W, Oliveira
|
|
ASB. Motor neuron disease with leukodystrophy due to CSF1R mutation.
|
|
Rev Neurol (Paris). 2020;176:219-21.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/31522743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31522743</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sriram.2022.311">Sriram
|
|
N, Padmanabha
|
|
H, Chandra
|
|
SR, Mahale
|
|
R, Nandeesh
|
|
B, Bhat
|
|
MD, Christopher
|
|
R, Gupta
|
|
M, Udupi
|
|
GA, Mailankody
|
|
P, Mathuranath
|
|
PS. CSF1R related leukoencephalopathy - rare childhood presentation of an autosomal dominant microgliopathy!
|
|
Ann Indian Acad Neurol.
|
|
2022;25:311-4.
|
|
[<a href="/pmc/articles/PMC9175392/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9175392</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35693676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35693676</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.stabile.2016.1565">Stabile
|
|
C, Taglia
|
|
I, Battisti
|
|
C, Bianchi
|
|
S, Federico
|
|
A. Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): update on molecular genetics.
|
|
Neurol Sci.
|
|
2016;37:1565-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27338940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27338940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sundal.2015.328">Sundal
|
|
C, Baker
|
|
M, Karrenbauer
|
|
V, Gustavsen
|
|
M, Bedri
|
|
S, Glaser
|
|
A, Myhr
|
|
KM, Haugarvoll
|
|
K, Zetterberg
|
|
H, Harbo
|
|
H, Kockum
|
|
I, Hillert
|
|
J, Wszolek
|
|
Z, Rademakers
|
|
R, Andersen
|
|
O. Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis.
|
|
Eur J Neurol.
|
|
2015;22:328-33.
|
|
[<a href="/pmc/articles/PMC4289423/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4289423</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25311247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25311247</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sundal.2019.188">Sundal
|
|
C, Carmona
|
|
S, Yhr
|
|
M, Almström
|
|
O, Ljungberg
|
|
M, Hardy
|
|
J, Hedberg-Oldfors
|
|
C, Fred
|
|
Å, Brás
|
|
J, Oldfors
|
|
A, Andersen
|
|
O, Guerreiro
|
|
R.
|
|
An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids.
|
|
Acta Neuropathol Commun.
|
|
2019;7:188.
|
|
[<a href="/pmc/articles/PMC6880494/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6880494</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31775912" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31775912</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sundal.2013.869">Sundal
|
|
C, Fujioka
|
|
S, Van Gerpen
|
|
JA, Wider
|
|
C, Nicholson
|
|
AM, Baker
|
|
M, Shuster
|
|
EA, Aasly
|
|
J, Spina
|
|
S, Ghetti
|
|
B, Roeber
|
|
S, Garbern
|
|
J, Tselis
|
|
A, Swerdlow
|
|
RH, Miller
|
|
BB, Borjesson-Hanson
|
|
A, Uitti
|
|
RJ, Ross
|
|
OA, Stoessl
|
|
AJ, Rademakers
|
|
R, Josephs
|
|
KA, Dickson
|
|
DW, Broderick
|
|
D, Wszolek
|
|
ZK. Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations.
|
|
Parkinsonism Relat Disord.
|
|
2013;19:869-77.
|
|
[<a href="/pmc/articles/PMC3977389/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3977389</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23787135" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23787135</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sundal.2014.444">Sundal
|
|
C, Jönsson
|
|
L, Ljungberg
|
|
M, Zhong
|
|
J, Tian
|
|
W, Zhu
|
|
T, Linden
|
|
T, Börjesson-Hanson
|
|
A, Andersen
|
|
O, Ekholm
|
|
S. Different stages of white matter changes in the original HDLS family revealed by advanced MRI techniques.
|
|
J Neuroimaging.
|
|
2014;24:444-52.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23751174" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23751174</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.sundal.2012.566">Sundal
|
|
C, Van Gerpen
|
|
JA, Nicholson
|
|
AM, Wider
|
|
C, Shuster
|
|
EA, Aasly
|
|
J, Spina
|
|
S, Ghetti
|
|
B, Roeber
|
|
S, Garbern
|
|
J, Borjesson-Hanson
|
|
A, Tselis
|
|
A, Swerdlow
|
|
RH, Miller
|
|
BB, Fujioka
|
|
S, Heckman
|
|
MG, Uitti
|
|
RJ, Josephs
|
|
KA, Baker
|
|
M, Andersen
|
|
O, Rademakers
|
|
R, Dickson
|
|
DW, Broderick
|
|
D, Wszolek
|
|
ZK. MRI characteristics and scoring in HDLS due to CSF1R gene mutations.
|
|
Neurology.
|
|
2012;79:566–74.
|
|
[<a href="/pmc/articles/PMC3413763/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3413763</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22843259" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22843259</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.tamhankar.2020.302">Tamhankar
|
|
PM, Zhu
|
|
B, Tamhankar
|
|
VP, Mithbawkar
|
|
S, Seabra
|
|
L, Livingston
|
|
JH, Ikeuchi
|
|
T, Crow
|
|
YJ. A novel hypomorphic CSF1R gene mutation in the biallelic state leading to fatal childhood neurodegeneration.
|
|
Neuropediatrics.
|
|
2020;51:302–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/32464672" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32464672</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.tipton.2021.2901">Tipton
|
|
PW, Kenney-Jung
|
|
D, Rush
|
|
BK, Middlebrooks
|
|
EH, Nascene
|
|
D, Singh
|
|
B, Holtan
|
|
S, Ayala
|
|
E, Broderick
|
|
DF, Lund
|
|
T, Wszolek
|
|
ZK. Treatment of CSF1R-related leukoencephalopathy: breaking new ground.
|
|
Mov Disord.
|
|
2021;36:2901-9.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/34329526" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34329526</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.tutuncu.2013.188">Tutuncu
|
|
M, Tang
|
|
J, Zeid
|
|
NA, Kale
|
|
N, Crusan
|
|
DJ, Atkinson
|
|
EJ, Siva
|
|
A, Pittock
|
|
SJ, Pirko
|
|
I, Keegan
|
|
BM, Lucchinetti
|
|
CF, Noseworthy
|
|
JH, Rodriguez
|
|
M, Weinshenker
|
|
BG, Kantarci
|
|
OH. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.
|
|
Mult Scler.
|
|
2013;19:188-98.
|
|
[<a href="/pmc/articles/PMC4029334/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4029334</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22736750" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22736750</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.van_der_knaap.2000.463">van der Knaap
|
|
MS, Naidu
|
|
S, Kleinschmidt-Demasters
|
|
BK, Kamphorst
|
|
W, Weinstein
|
|
HC. Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids.
|
|
Neurology.
|
|
2000;54:463-8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10668715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10668715</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.van_gerpen.2008.925">Van Gerpen
|
|
JA, Wider
|
|
C, Broderick
|
|
DF, Dickson
|
|
DW, Brown
|
|
LA, Wszolek
|
|
ZK. Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids.
|
|
Neurology.
|
|
2008;71:925–9.
|
|
[<a href="/pmc/articles/PMC2843529/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2843529</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18794495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18794495</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.wu.2024.798">Wu
|
|
J, Cheng
|
|
X, Ji
|
|
D, Niu
|
|
H, Yao
|
|
S, Lv
|
|
X, Wang
|
|
J, Li
|
|
Z, Zheng
|
|
H, Cao
|
|
Y, Zhan
|
|
F, Zhang
|
|
M, Tian
|
|
W, Huang
|
|
X, Luan
|
|
X, Cao
|
|
L. The phenotypic and genotypic spectrum of CSF1R-related disorder in China.
|
|
Mov Disord.
|
|
2024;39:798-813.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/38465843" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38465843</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hdls.REF.wu.2022.3265">Wu
|
|
X, Sun
|
|
C, Wang
|
|
X, Liu
|
|
Y, Wu
|
|
W, Jia
|
|
G. Identification of a de novo splicing mutation in the CSF1R gene in a Chinese patient with hereditary diffuse leukoencephalopathy with spheroids.
|
|
Neurol Sci.
|
|
2022;43:3265-72.
|
|
[<a href="/pmc/articles/PMC9018673/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9018673</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34791569" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34791569</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK100239_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Jaroslaw Dulski</span>, MD, PhD<div class="affiliation small">Department of Neurology<br />Mayo Clinic<br />Jacksonville, Florida</div><div class="affiliation small">Division of Neurological and Psychiatric Nursing<br />Faculty of Health Sciences<br />Medical University of Gdansk<br />Gdansk, Poland</div><div class="affiliation small">Neurology Department<br />St Adalbert Hospital<br />Copernicus PL Ltd<br />Gdansk, Poland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.oyam@walsoraj.ikslud" class="oemail">ude.oyam@walsoraj.ikslud</a><span style="unicode-bidi: bidi-override; direction: ltr;">; </span><a href="mailto:dev@null" data-email="lp.ude.demug@ikslud.walsoraj" class="oemail">lp.ude.demug@ikslud.walsoraj</a><div></div></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Christina Sundal</span>, MD, PhD<div class="affiliation small">NeuroClinicNorway<br />Lillestrøm, Norway</div><div class="affiliation small">Department of Neuromedicine and Movement Science<br />Norwegian University of Science and Technology<br />Trondheim, Norway</div><div class="affiliation small">NorHEAD<br />Norwegian Centre for Headache Research<br />Norway<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@ladnushanitsirhc" class="oemail">moc.liamg@ladnushanitsirhc</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Zbigniew K Wszolek</span>, MD<div class="affiliation small">Department of Neurology<br />Mayo Clinic<br />Jacksonville, Florida<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.oyam@weingibz.kelozsw" class="oemail">ude.oyam@weingibz.kelozsw</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">August 30, 2012</span>; Last Update: <span itemprop="dateModified">April 4, 2024</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Dulski J, Sundal C, Wszolek ZK. CSF1R-Related Disorder. 2012 Aug 30 [Updated 2024 Apr 4]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/psach/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/ctcf-dis/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobhdlsTcsf1rrelateddisorderphenotypic"><div id="hdls.T.csf1rrelated_disorder_phenotypic" class="table"><div class="caption"><p><i>CSF1R</i>-Related Disorder: Phenotypic Continuum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_phenotypic/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.csf1rrelated_disorder_phenotypic_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_1" style="text-align:left;vertical-align:middle;">Proposed Terminology <sup>1</sup></th><th id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;"><i>CSF1R</i> Genotype</th><th id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_3" style="text-align:left;vertical-align:middle;">Manifestations</th><th id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_4" style="text-align:left;vertical-align:middle;">Encompassed Terminology <sup>2</sup></th></tr><tr><th headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2" id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Biallelic PVs</th><th headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2" id="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monoallelic PV</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Early-onset <i>CSF1R</i>-related disorder</b><br />(age <18 yrs)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2 hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typical</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2 hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neurologic manifestations</div></li><li class="half_rhythm"><div>Skeletal abnormalities</div></li><li class="half_rhythm"><div>Nonspecific dysmorphic facial features</div></li><li class="half_rhythm"><div>Congenital brain abnormalities</div></li></ul>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain abnormalities, neurodegeneration, & dysosteosclerosis (BANDDOS)</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Late-onset <i>CSF1R</i>-related disorder</b><br />(age ≥18 yrs)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2 hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_2 hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typical</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically limited to neurologic manifestations (progressive neurologic decline)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_phenotypic_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Adult-onset leukoencephalopathy w/axonal spheroids & pigmented glia (ALSP)</div></li><li class="half_rhythm"><div>Pigmentary orthochromatic leukodystrophy (POLD)</div></li><li class="half_rhythm"><div><i>CSF1R</i>-related leukoencephalopathy</div></li><li class="half_rhythm"><div>Hereditary diffuse leukoencephalopathy w/spheroids (HDLS) <sup>3</sup></div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Adapted from <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al [2024]</a>, Table 1</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">PV = pathogenic variant</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.d.1"><p class="no_margin">
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<a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al [2024]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hdls.TF.d.2"><p class="no_margin">See <a href="#hdls.Nomenclature">Nomenclature</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hdls.TF.d.3"><p class="no_margin">The original Swedish family with HDLS had a heterozygous pathogenic variant in <i>AARS1</i> (see <a href="#hdls.Differential_Diagnosis">Differential Diagnosis</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTmoleculargenetictestingusedin"><div id="hdls.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>CSF1R</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CSF1R</i>
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</td><td headers="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>95%% <sup>4</sup></td></tr><tr><td headers="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Copy number & gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_hdls.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><5% <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.1.1"><p class="no_margin">See <a href="/books/NBK100239/?report=reader#hdls.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hdls.TF.1.2"><p class="no_margin">See <a href="#hdls.Molecular_Genetics">Molecular Genetics</a> for information on variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hdls.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hdls.TF.1.4"><p class="no_margin">Several intronic variants outside of the canonical splice junction typically included by standard sequencing have been reported [<a class="bibr" href="#hdls.REF.rademakers.2011.200" rid="hdls.REF.rademakers.2011.200">Rademakers et al 2011</a>, <a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al 2017</a>, <a class="bibr" href="#hdls.REF.wu.2022.3265" rid="hdls.REF.wu.2022.3265">Wu et al 2022</a>]. These and other deep intronic variants may be detected by genome sequencing.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hdls.TF.1.5"><p class="no_margin">Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by <a class="bibr" href="#hdls.REF.ishiguro.2023.1861" rid="hdls.REF.ishiguro.2023.1861">Ishiguro et al [2023]</a>) may not be detected by these methods. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="hdls.TF.1.6"><p class="no_margin">To date, a few large intragenic deletions have been reported in individuals with <i>CSF1R</i>-related disorder [<a class="bibr" href="#hdls.REF.ishiguro.2023.1861" rid="hdls.REF.ishiguro.2023.1861">Ishiguro et al 2023</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTcsf1rrelateddisorderfrequencyo"><div id="hdls.T.csf1rrelated_disorder_frequency_o" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>CSF1R</i>-Related Disorder: Frequency of Select Features by Age of Onset</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_frequency_o/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.csf1rrelated_disorder_frequency_o_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early Onset (n=19) <sup>1</sup></th><th id="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late Onset (n=122)<br />(% of affected) <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic manifestations</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15/17</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile-onset hypotonia</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3/11</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not reported</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/14</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not reported</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech abnormalities</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/15</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">52%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cognitive impairment</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/14</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">94%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Parkinsonism</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/15 <sup>3</sup></td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">74%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pyramidal signs</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/15</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">57%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizures</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9/16</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysphagia</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9/12</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Optic nerve atrophy</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2/7</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>4</sup></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Brain imaging abnormalities</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19/19</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">White matter abnormalities</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19/19</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">81%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Calcifications</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15/18</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">75%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain atrophy</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 5.</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">64%-92%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Callosal abnormalities</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/16 <sup>6</sup></td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">49% <sup>7</sup></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ventriculomegaly</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/19</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dandy-Walker malformations</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/19</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 8.</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Malformations of cortical development</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/10</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>4</sup></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Skeletal abnormalities</b> (clinical and/or radiographic)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/17</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>4</sup></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysmorphic features</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/17</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_frequency_o_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>4</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.2.1"><p class="no_margin">
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<a class="bibr" href="#hdls.REF.dulski.2023c.160" rid="hdls.REF.dulski.2023c.160">Dulski et al [2023c]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hdls.TF.2.2"><p class="no_margin"><a class="bibr" href="#hdls.REF.konno.2017.37" rid="hdls.REF.konno.2017.37">Konno et al [2017]</a>, <a class="bibr" href="#hdls.REF.dulski.2024.105894" rid="hdls.REF.dulski.2024.105894">Dulski et al [2024]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hdls.TF.2.3"><p class="no_margin">Rigidity; no data on other parkinsonian features</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hdls.TF.2.4"><p class="no_margin">Reported in a few individuals</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hdls.TF.2.5"><p class="no_margin">Brain atrophy was evidenced both on neuroimaging and pathologic examination [<a class="bibr" href="#hdls.REF.oosterhof.2019.936" rid="hdls.REF.oosterhof.2019.936">Oosterhof et al 2019</a>, [<a class="bibr" href="#hdls.REF.sriram.2022.311" rid="hdls.REF.sriram.2022.311">Sriram et al 2022</a>]. Of note, data to date are limited in young persons, as it is difficult to differentiate atrophy from hypoplasia, especially when neuroimaging has been performed just once.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="hdls.TF.2.6"><p class="no_margin">Agenesis</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="hdls.TF.2.7"><p class="no_margin">Atrophy [<a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="hdls.TF.2.8"><p class="no_margin">Arnold-Chiari malformation, another posterior fossa malformation, has been reported [<a class="bibr" href="#hdls.REF.guo.2019.925" rid="hdls.REF.guo.2019.925">Guo et al 2019</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTgeneticdisorderstoconsiderin"><div id="hdls.T.genetic_disorders_to_consider_in" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genetic Disorders to Consider in the Differential Diagnosis of <i>CSF1R</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.genetic_disorders_to_consider_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.genetic_disorders_to_consider_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Disorder</th></tr><tr><th headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4" id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<i>CSF1R</i>-related disorder</th><th headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4" id="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from <i>CSF1R</i>-related disorder</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Disorders of interest in the differential diagnosis of early-onset <i>CSF1R</i>-related disorder</b>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ABCD1</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/x-ald/?report=reader">X-linked adrenoleukodystrophy</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognitive decline, dementia</div></li><li class="half_rhythm"><div>Spastic paraparesis</div></li></ul>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neuropathy & slowly spastic paraparesis</div></li><li class="half_rhythm"><div>WML are contrast enhancing.</div></li><li class="half_rhythm"><div>Corticospinal tracts are involved from cranial to medulla.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ADAR</i>
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<br />
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<i>IFIH1</i>
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<br />
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<i>RNASEH2A</i>
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<br />
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<i>RNASEH2B</i>
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<br />
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<i>RNASEH2C</i>
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<br />
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<i>SAMHD1</i>
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<br />
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<i>TREX1</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ags/?report=reader">Aicardi-Goutières syndrome</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chilblain skin lesions</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AQP4</i>
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<br />
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<i>GPRC5B</i>
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<br />
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<i>HEPACAM</i>
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<br />
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<i>MLC1</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mlc/?report=reader">Megalencephalic leukoencephalopathy w/subcortical cysts</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Subcortical cysts on neuroimaging</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ARSA</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult metachromatic leukodystrophy (See <a href="/books/n/gene/mld/?report=reader">Arylsulfatase A Deficiency</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Executive dysfunction, personality changes, memory issues</div></li><li class="half_rhythm"><div>Pyramidal signs, seizures</div></li></ul>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Peripheral neuropathy</div></li><li class="half_rhythm"><div>Spread of WML into the cerebellar region & WM myelin breakdown w/low-density tigroid stripes</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ASPA</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/canavan/?report=reader">Canavan disease</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neurodegeneration</div></li><li class="half_rhythm"><div>Macrocephaly</div></li></ul>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rostrocaudal progression of myelin loss on serial imaging studies</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATP7A</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Menkes disease (See <a href="/books/n/gene/menkes/?report=reader"><i>ATP7A</i>-Related Copper Transport Disorders</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neuropathy</div></li><li class="half_rhythm"><div>"Occipital horns"</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>C9orf72</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/als-ftd/?report=reader"><i>C9orf72</i> frontotemporal dementia &/or amyotrophic lateral sclerosis</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontal &/or temporal atrophy w/far fewer WML</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHMP2B</i>
|
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<a href="/books/n/gene/ftd-chmp2b/?report=reader"><i>CHMP2B</i> frontotemporal dementia</a>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontal &/or temporal atrophy w/far fewer WML</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CLN3</i>
|
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<br />
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<i>CLN5</i>
|
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<br />
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<i>CLN6</i>
|
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<br />
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<i>CLN8</i>
|
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<br />
|
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<i>CTSD</i>
|
|
<br />
|
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<i>CTSF</i>
|
|
<br />
|
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<i>DNAJC5</i>
|
|
<br />
|
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<i>GRN</i>
|
|
<br />
|
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<i>KCTD7</i>
|
|
<br />
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<i>MFSD8</i>
|
|
<br />
|
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<i>PPT1</i>
|
|
<br />
|
|
<i>TPP1</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuronal ceroid lipofuscinoses (OMIM <a href="https://omim.org/phenotypicSeries/PS256730" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS256730</a>)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD <sup>1</sup></td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Retinal degeneration</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>DARS2</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/lbsl/?report=reader">Leukoencephalopathy w/brain stem & spinal cord involvement & lactate elevation</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Slowly progressive pyramidal, cerebellar, & dorsal column dysfunction</div></li><li class="half_rhythm"><div>Deterioration of motor skills</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Peripheral neuropathy</div></li><li class="half_rhythm"><div>WML are either non-homogeneous/spotty or homogeneous & confluent.</div></li><li class="half_rhythm"><div>Signal abnormalities are evident in the medullary pyramids, dorsal columns, & lateral corticospinal tracts.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EIF2B1</i>
|
|
<br />
|
|
<i>EIF2B2</i>
|
|
<br />
|
|
<i>EIF2B3</i>
|
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<br />
|
|
<i>EIF2B4</i>
|
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<br />
|
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<i>EIF2B5</i>
|
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cach/?report=reader">Childhood ataxia w/central nervous system hypomyelination / vanishing white matter</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognitive decline</div></li><li class="half_rhythm"><div>Spastic paraparesis</div></li><li class="half_rhythm"><div>Cerebellar ataxia</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Stress-induced deterioration w/minor trauma or infections</div></li><li class="half_rhythm"><div>More widespread & diffuse WM changes & atrophy than in <i>CSF1R</i>-related disorder</div></li><li class="half_rhythm"><div>Cystic breakdown of WM</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>ERCC6</i>
|
|
<br />
|
|
<i>ERCC8</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cockayne/?report=reader">Cockayne syndrome</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Peripheral neuropathy</div></li><li class="half_rhythm"><div>Progressive microcephaly</div></li></ul>
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|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GALC</i>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/krabbe/?report=reader">Krabbe disease</a>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pyramidal signs, developing into para- or tetraparesis</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Peripheral neuropathy</div></li><li class="half_rhythm"><div>MRI shows predominance in posterior part of WM</div></li><li class="half_rhythm"><div>MRI detects demyelination in brain stem & cerebellum</div></li><li class="half_rhythm"><div>T<sub>2</sub>-weighted value is progressively prolonged in occipital deep WM & posterior part of central semiovale in late-onset disease.</div></li></ul>
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|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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|
<i>GCDH</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/glutaric-a1/?report=reader">Glutaric acidemia type 1</a>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progressive macrocephaly</div></li><li class="half_rhythm"><div>Acute exacerbations of neurologic deficits</div></li></ul>
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|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GFAP</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/alexander/?report=reader">Alexander disease</a>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Palatal myoclonus</div></li><li class="half_rhythm"><div>Cognitive function in adults is frequently normal.</div></li><li class="half_rhythm"><div>Infratentorial atrophy on MRI</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GLA</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/fabry/?report=reader">Fabry disease</a>
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|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">WML</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gray matter pathology</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GLB1</i>
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|
<br />
|
|
<i>GM2A</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GM1 & GM2 gangliosidoses (See <a href="/books/n/gene/gm1-ganglio/?report=reader"><i>GLB1</i>-Related Disorders</a> and <a href="/books/n/gene/gm2a-def/?report=reader">GM2 Activator Deficiency</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skin & eye changes</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GRN</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ftd-grn/?report=reader"><i>GRN</i> frontotemporal dementia</a>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontal &/or temporal atrophy w/far fewer WML</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>LMNB1</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/lad-ad/?report=reader"><i>LMNB1</i>-related autosomal dominant leukodystrophy</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognitive impairment</div></li><li class="half_rhythm"><div>Pyramidal & cerebellar signs</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Early autonomic dysfunction</div></li><li class="half_rhythm"><div>Periventricular normal rim on MRI</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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|
<i>MAPT</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ftdp-17/?report=reader"><i>MAPT</i>-related frontotemporal dementia</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progresses over a few yrs into profound dementia w/mutism</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontal &/or temporal atrophy w/far fewer WML</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>NOTCH3</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/cadasil/?report=reader">CADASIL</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Frontal lobe syndrome</div></li><li class="half_rhythm"><div>WML</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Stroke-like clinical signs</div></li><li class="half_rhythm"><div>Multiple cerebral infarcts & WML incl characteristic temporal pools</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>NPC1</i>
|
|
<br />
|
|
<i>NPC2</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/npc/?report=reader">Niemann-Pick disease type C</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Visceral manifestations</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>PLP1</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pelizaeus-Merzbacher disease (See <a href="/books/n/gene/pmd/?report=reader"><i>PLP1</i> Disorders</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical & neuroimaging findings</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>POLR1C</i>
|
|
<br />
|
|
<i>POLR3A</i>
|
|
<br />
|
|
<i>POLR3B</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/pol3-leuk/?report=reader">POLR3-related leukodystrophy</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neurologic deficits</div></li><li class="half_rhythm"><div>Abnormal dentition</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Endocrine abnormalities</div></li><li class="half_rhythm"><div>Progressive myopia</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SUMF1</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/m-sulfatase-def/?report=reader">Multiple sulfatase deficiency</a> (Austin disease)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodegeneration</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Organomegaly</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TREM2</i>
|
|
<br />
|
|
<i>TYROBP</i>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/plosl/?report=reader">Polycystic lipomembranous osteodysplasia w/sclerosing leukoencephalopathy</a> (Nasu-Hakola disease)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Insidious personality changes, frontal lobe syndrome</div></li><li class="half_rhythm"><div>Motor impairments</div></li><li class="half_rhythm"><div>Dementia & progression to vegetative state</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Pain/tenderness of feet/wrists</div></li><li class="half_rhythm"><div>Polycystic osseous lesions, pathologic fractures</div></li><li class="half_rhythm"><div>U-fibers partially affected</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>350 genes <sup>2</sup></td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/mt-overview/?report=reader">Primary mitochondrial disorders</a>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR<br />Mat<br />XL</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Neurodegeneration</div></li><li class="half_rhythm"><div>Brain calcifications</div></li></ul>
|
|
</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skin photosensitivity</div></li><li class="half_rhythm"><div>Distinct physical appearance</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Disorders of interest in the differential diagnosis of late-onset <i>CSF1R</i>-related disorder</b>
|
|
</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>AARS1</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AARS1</i>-related leukoencephalopathy (Swedish hereditary diffuse leukoencephalopathy with spheroids) (OMIM <a href="https://omim.org/entry/619661" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619661</a>)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotypic mimic of late-onset <i>CSF1R</i>-related disorder</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuroimaging pattern w/centrifugally expanding rim of ↓ diffusion (evidenced on MRI diffusion-weighted/tensor imaging) through WM around anterior ventricular horns</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AARS2</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AARS2-</i>related leukoencephalopathy (See <a href="/books/n/gene/aars2-dis/?report=reader"><i>AARS2</i>-Related Disorder</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotypic mimic of late-onset <i>CSF1R</i>-related disorder</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Premature ovarian insufficiency in all females</div></li><li class="half_rhythm"><div>WM demonstrates rarefaction.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>APP</i>
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<br />
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<i>PSEN1</i>
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<br />
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<i>PSEN2</i>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-onset familial Alzheimer disease (See <a href="/books/n/gene/alzheimer/?report=reader">Alzheimer Disease Overview</a>.)</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Executive dysfunction, personality changes</div></li><li class="half_rhythm"><div>Similar age of onset</div></li></ul>
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</td><td headers="hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_1_4 hd_h_hdls.T.genetic_disorders_to_consider_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Episodic memory loss</div></li><li class="half_rhythm"><div>WM changes are present but much less pronounced.</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; CADASIL = <i>c</i>erebral <i>a</i>utosomal <i>d</i>ominant <i>a</i>rteriopathy with <i>s</i>ubcortical <i>i</i>nfarcts and <i>l</i>eukoencephalopathy; MOI = mode of inheritance; Mat = maternal; WM = white matter; WML = white matter lesions; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hdls.TF.3.1"><p class="no_margin">Except for <i>DNAJC5</i>-related neuronal ceroid lipofuscinosis (which is inherited in an autosomal dominant manner), neuronal ceroid lipofuscinoses are inherited in an autosomal recessive manner.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hdls.TF.3.2"><p class="no_margin">
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<a class="bibr" href="#hdls.REF.mccormick.2018.714" rid="hdls.REF.mccormick.2018.714">McCormick et al [2018]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTcsf1rrelateddisorderrecommended"><div id="hdls.T.csf1rrelated_disorder_recommended" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>CSF1R</i>-Related Disorder: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.csf1rrelated_disorder_recommended_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic deficits</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete neurologic assessment</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Incl screening for cognitive impairment</div></li><li class="half_rhythm"><div>Assessment for motor impairment incl gait, bradykinesia, rigidity, & tremor; sensory deficits; & bulbar signs</div></li><li class="half_rhythm"><div>When seizures are suspected, an EEG or video EEG is recommended</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cognitive abilities & neurobehavioral/psychiatric manifestations</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to psychologist &/or neuropsychologist as needed</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assessment of cognitive function (executive function, language processing, visuospatial/visuoconstructional skills)</div></li><li class="half_rhythm"><div>Assessment for anxiety, depression, apathy, indifference, abulia, disinhibition, distraction, & other behavioral or personality changes</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech-language pathologist eval</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assessment of need for speech therapy</div></li><li class="half_rhythm"><div>Consider need for alternative & augmentative communication.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysphagia</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrointestinal &/or feeding therapist eval</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Incl nutritional assessment, safety of oral feedings</div></li><li class="half_rhythm"><div>Consider need for gastrostomy tube placement.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal/ADL</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary care / orthopedics / physical medicine & rehab / PT eval</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl assessment of:
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<ul><li class="half_rhythm"><div>Skeletal system (incl radiographs)</div></li><li class="half_rhythm"><div>Muscle tone; joint range of motion; posture; mobility; strength, coordination, & endurance; pain; & bedsores</div></li><li class="half_rhythm"><div>Need for adaptive devices</div></li><li class="half_rhythm"><div>Footwear needs</div></li><li class="half_rhythm"><div>PT needs</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">OT</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess small motor function</div></li><li class="half_rhythm"><div>To assess ADL</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal issues</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary care physician &/or gastroenterologist</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for constipation, incontinence</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision deficits</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Detailed ophthalmologic eval, incl assessment of visual acuity, visual fields, & intraocular pressure</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of <i>CSF1R</i>-related disorder to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine availability of adequate support systems</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Direct families / affected persons to community or <a href="#hdls.Resources">online resources</a>.</div></li><li class="half_rhythm"><div>Social work involvement for parental support</div></li><li class="half_rhythm"><div>Home nursing referral</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTcsf1rrelateddisordersymptomatic"><div id="hdls.T.csf1rrelated_disorder_symptomatic" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>CSF1R-</i>Related Disorder: Symptomatic Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_symptomatic/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.csf1rrelated_disorder_symptomatic_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cognitive decline / Dementia</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognitive behavioral therapy</div></li><li class="half_rhythm"><div>Psychotherapy & psychoeducational interventions</div></li></ul>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neuropsychiatric manifestations</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Psychotherapy / neuropsychological rehab</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To date, standard treatment for psychiatric manifestations (e.g., depression, suicidal tendencies, anxiety, & psychosis) have not had long-term benefit.</div></li><li class="half_rhythm"><div>Antipsychotics are not recommended in general due to extrapyramidal side effects but may be used in persons who have issues with aggression.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Motor dysfunction</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Pyramidal signs</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Botulinum toxin for spasticity</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Parkinsonism</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Levodopa or other dopaminergic therapies</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most persons do not benefit from levodopa. 1 However, a trial with slowly titrated dose up to 1,000 mg/day is warranted to determine individual response.</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" rowspan="2" colspan="2" scope="row" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal/ADL</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Transfers (e.g., from bed to wheelchair, wheelchair to car)</div></li><li class="half_rhythm"><div>Training on fall techniques to minimize risk of injury</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">OT</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To accomplish tasks such as mobility, washing, dressing, eating, cooking, & grooming</div></li><li class="half_rhythm"><div>To assist w/household modifications to meet special needs</div></li></ul>
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</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech-language therapy</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider alternative means of communication.</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysphagia</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating feeding team</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assure adequate nutrition & minimize risk of aspiration</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Seizures</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ASM</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>General & recurrent infections</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use of antibiotics to treat general & recurrent infections such as pneumonia &/or urinary tract infections</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/Community</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Education</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_symptomatic_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Social issues (unemployment, divorce, financial challenges, &/or alcohol addiction) & suicidal tendencies are often assoc w/progression of disease.</div></li><li class="half_rhythm"><div>Some of the social consequences may be avoided if family members are informed early re nature of disorder.</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; ASM = anti-seizure medications; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.5.1"><p class="no_margin">
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<a class="bibr" href="#hdls.REF.sundal.2013.869" rid="hdls.REF.sundal.2013.869">Sundal et al [2013]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsTcsf1rrelateddisorderrecommended1"><div id="hdls.T.csf1rrelated_disorder_recommended_1" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>CSF1R-</i>Related Disorder: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.T.csf1rrelated_disorder_recommended_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.T.csf1rrelated_disorder_recommended_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic &</b>
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<br />
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<b>neuropsychiatric deficits</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By neurologist & neuropsychologist for ↑ severity / new manifestations <sup>1</sup></td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Symptomatic persons: every 6 mos or as needed</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">By specialist in physical medicine & rehab / PT</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Brain MRI (preferably 3 or 7 Tesla)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 12 mos or as needed</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Feeding/Nutrition</b><br />(esp difficulty w/swallowing &/or weight loss & need to consider gastrostomy tube placement)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By feeding team</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating feeding team</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal issues</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By primary care doctor</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 12 mos or as needed</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision problems</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By ophthalmologist</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating ophthalmologist</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Musculoskeletal/ADL</b><br />(including development of contractures &/or changes in mobility)</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By PT/OT</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating PT/OT</td></tr><tr><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/Community</b>
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</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).</td><td headers="hd_h_hdls.T.csf1rrelated_disorder_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; OT = occupational therapist; PT = physical therapist</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hdls.TF.6.1"><p class="no_margin">Recommended frequency of these evaluations depends on the age of the asymptomatic family member and the average age of disease onset in the family: (a) annually for individuals twenty or more years younger than the average age of disease onset in their family and (b) every six months for individuals approaching the age of expected symptomatic disease onset [Authors, unpublished observations].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsmolgenTA"><div id="hdls.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>CSF1R-Related Disorder: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_hdls.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_hdls.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_hdls.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_hdls.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_hdls.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_hdls.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/1436" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CSF1R</i>
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</a>
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</td><td headers="hd_b_hdls.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1436" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">5q32</a>
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</td><td headers="hd_b_hdls.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/P07333" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Macrophage colony-stimulating factor 1 receptor</a>
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</td><td headers="hd_b_hdls.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CSF1R" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CSF1R</a>
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</td><td headers="hd_b_hdls.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CSF1R[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CSF1R</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="hdls.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhdlsmolgenTB"><div id="hdls.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for CSF1R-Related Disorder (<a href="/omim/164770,221820" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK100239/table/hdls.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hdls.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/164770" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">164770</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COLONY-STIMULATING FACTOR 1 RECEPTOR; CSF1R</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/221820" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">221820</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS 1; HDLS1</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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