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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>HNRNPU-Related Neurodevelopmental Disorder - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="HNRNPU-Related Neurodevelopmental Disorder">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2022/03/10">
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<meta name="citation_author" content="Meena Balasubramanian">
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<meta name="citation_pmid" content="35274911">
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<meta name="citation_keywords" content="Developmental and Epileptic Encephalopathy 54">
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<meta name="citation_keywords" content="Early Infantile Epileptic Encephalopathy Type 54">
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<meta name="citation_keywords" content="Early Infantile Epileptic Encephalopathy Type 54">
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<meta name="citation_keywords" content="Developmental and Epileptic Encephalopathy 54">
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<meta name="citation_keywords" content="Heterogeneous nuclear ribonucleoprotein U">
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<meta name="citation_keywords" content="HNRNPU">
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<meta name="citation_keywords" content="HNRNPU-Related Neurodevelopmental Disorder">
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<meta name="DC.Title" content="HNRNPU-Related Neurodevelopmental Disorder">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Meena Balasubramanian">
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<meta name="DC.Date" content="2022/03/10">
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<meta name="description" content="HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) is characterized by developmental delay and intellectual disability – typically moderate to severe – with speech and language delay and/or absent speech. Affected individuals may also display autistic features. There may be feeding difficulties during the neonatal period as well as hypotonia, which often remains lifelong. Dysmorphic features have been described but they are nonspecific. Affected individuals are likely to experience seizures (most commonly tonic-clonic or absence) that may be refractory to treatment. Nonspecific brain MRI findings include ventriculomegaly and thinning of the corpus callosum. Less common findings include cardiac abnormalities, strabismus, undescended testes in males, renal anomalies, and skeletal features, including joint laxity, polydactyly, and scoliosis. Rarely, abnormal breathing patterns, including hyperventilation and apnea, may be present and can lead to sleep disturbance.">
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<meta name="og:description" content="HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) is characterized by developmental delay and intellectual disability – typically moderate to severe – with speech and language delay and/or absent speech. Affected individuals may also display autistic features. There may be feeding difficulties during the neonatal period as well as hypotonia, which often remains lifelong. Dysmorphic features have been described but they are nonspecific. Affected individuals are likely to experience seizures (most commonly tonic-clonic or absence) that may be refractory to treatment. Nonspecific brain MRI findings include ventriculomegaly and thinning of the corpus callosum. Less common findings include cardiac abnormalities, strabismus, undescended testes in males, renal anomalies, and skeletal features, including joint laxity, polydactyly, and scoliosis. Rarely, abnormal breathing patterns, including hyperventilation and apnea, may be present and can lead to sleep disturbance.">
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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="_NBK578573_"><span class="title" itemprop="name"><i>HNRNPU</i>-Related Neurodevelopmental Disorder</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Developmental and Epileptic Encephalopathy 54, Early Infantile Epileptic Encephalopathy Type 54</div><p class="contribs">Balasubramanian M.</p><p class="fm-aai"><a href="#_NBK578573_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 23 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hnrnpu-ndd.Summary" itemprop="description"><h2 id="_hnrnpu-ndd_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>HNRNPU</i>-related neurodevelopmental disorder (<i>HNRNPU</i>-NDD) is characterized by developmental delay and intellectual disability – typically moderate to severe – with speech and language delay and/or absent speech. Affected individuals may also display autistic features. There may be feeding difficulties during the neonatal period as well as hypotonia, which often remains lifelong. Dysmorphic features have been described but they are nonspecific. Affected individuals are likely to experience seizures (most commonly tonic-clonic or absence) that may be refractory to treatment. Nonspecific brain MRI findings include ventriculomegaly and thinning of the corpus callosum. Less common findings include cardiac abnormalities, strabismus, undescended testes in males, renal anomalies, and skeletal features, including joint laxity, polydactyly, and scoliosis. Rarely, abnormal breathing patterns, including hyperventilation and apnea, may be present and can lead to sleep disturbance.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>HNRNPU</i>-NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant in <i>HNRNPU</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations</i>: Standard treatment of seizures with anti-seizure medications (sodium valproate is often used and is frequently effective); consider instituting the ketogenic diet and/or newer generation anti-seizure medications in those with refractory seizures. Feeding therapy; consider a temporary or permanent feeding tube for those with persistent feeding issues. Consider supplemental oxygen, CPAP, or BiPAP in those with sleep apnea. Standard treatment for tone abnormalities, intellectual disability, behavioral problems, hyperventilation / abnormal breathing patterns, congenital heart defects, strabismus, hearing loss, renal anomalies, undescended testes, and limb defects.</p><p><i>Surveillance</i>: At each visit: measurement of growth parameters; evaluation of nutritional status and safety of oral intake; monitor for evidence of constipation, new seizures, hyperventilation, apnea, and changes in tone; assessment of developmental progress and behavior. Annually or as clinically indicated: ophthalmologic and audiologic evaluations.</p><p><i>Agents/circumstances to avoid:</i> Activities and agents that may induce seizures.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>HNRNPU</i>-NDD is expressed in an autosomal dominant manner and typically caused by a <i>de novo</i>
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<i>HNRNPU</i> pathogenic variant. The risk to other family members is hypothesized to be low. Presumed parental germline mosaicism has been reported in one family with two affected sibs. Once the <i>HNRNPU</i> pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.</p></div></div><div id="hnrnpu-ndd.Diagnosis"><h2 id="_hnrnpu-ndd_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for <i>HNRNPU</i>-related neurodevelopmental disorder (<i>HNRNPU</i>-NDD) have been published.</p><div id="hnrnpu-ndd.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>HNRNPU</i>-NDD <b>should be considered</b> in individuals with the following clinical and brain MRI findings.</p><p><b>Clinical findings</b> (presenting in infancy or childhood). Moderate-to-severe developmental delay (DD) or intellectual disability (ID) AND any of the following:</p><ul><li class="half_rhythm"><div>Generalized hypotonia of infancy</div></li><li class="half_rhythm"><div>Infant feeding difficulties</div></li><li class="half_rhythm"><div>Speech and language delay and/ or absent speech</div></li><li class="half_rhythm"><div>Autism spectrum disorder or autistic traits</div></li><li class="half_rhythm"><div>Nonspecific dysmorphic facial features (See <a href="#hnrnpu-ndd.Clinical_Description">Clinical Description</a>.)</div></li><li class="half_rhythm"><div>Epilepsy, including generalized tonic-clonic seizures and absence seizures</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Strabismus</div></li></ul><p><b>Brain MRI findings.</b> The most common brain MRI findings are nonspecific but include:</p><ul><li class="half_rhythm"><div>Ventriculomegaly</div></li><li class="half_rhythm"><div>Thinning of the corpus callosum</div></li></ul><p><b>Family history.</b> Because <i>HNRNPU</i>-NDD is typically caused by a <i>de novo</i> pathogenic variant, most probands represent a simplex case (i.e., a single occurrence in a family). However, a report of two affected sibs suggests the possibility of germline mosaicism in a parent [<a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>] (see <a href="#hnrnpu-ndd.Genetic_Counseling">Genetic Counseling</a>).</p></div><div id="hnrnpu-ndd.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>HNRNPU</i>-related neurodevelopmental disorder <b>is established</b> in a proband with <a href="#hnrnpu-ndd.Suggestive_Findings">suggestive findings</a> and a heterozygous pathogenic (or likely pathogenic) variant in <i>HNRNPU</i> identified by molecular genetic testing (see <a href="/books/NBK578573/table/hnrnpu-ndd.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobhnrnpunddTmoleculargenetictestingu">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#hnrnpu-ndd.REF.richards.2015.405" rid="hnrnpu-ndd.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a heterozygous <i>HNRNPU</i> variant of uncertain significance does not establish or rule out the diagnosis of this disorder.</p><p><b>Molecular genetic testing</b> in a child with developmental delay or an older individual with intellectual disability often begins with chromosomal microarray analysis (CMA). If CMA is not diagnostic, the next step is typically either a multigene panel or exome sequencing. Note: Single-gene testing (sequence analysis of <i>HNRNPU</i>, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Chromosomal microarray analysis (CMA)</b> uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>HNRNPU</i>) that cannot be detected by sequence analysis.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>An intellectual disability or epileptic encephalopathy multigene panel</b> that includes <i>HNRNPU</i> and other genes of interest (see <a href="#hnrnpu-ndd.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition in a person with a nondiagnostic CMA 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>. Of note, given the rarity of <i>HNRNPU</i>, some panels for intellectual disability may not include this gene. (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.</div><div class="half_rhythm">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>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used and yields results similar to an ID multigene panel with the additional advantage that exome sequencing includes genes recently identified as causing ID and/or epileptic encephalopathy whereas some multigene panels may not. <b>Genome sequencing</b> is also possible</div><div class="half_rhythm">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>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddTmoleculargenetictestingu"><a href="/books/NBK578573/table/hnrnpu-ndd.T.molecular_genetic_testing_u/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobhnrnpunddTmoleculargenetictestingu"><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="hnrnpu-ndd.T.molecular_genetic_testing_u"><a href="/books/NBK578573/table/hnrnpu-ndd.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobhnrnpunddTmoleculargenetictestingu">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>HNRNPU</i>-Related Neurodevelopmental Disorder </p></div></div></div></div><div id="hnrnpu-ndd.Clinical_Characteristics"><h2 id="_hnrnpu-ndd_Clinical_Characteristics_">Clinical Characteristics</h2><div id="hnrnpu-ndd.Clinical_Description"><h3>Clinical Description</h3><p>To date, 83 individuals have been identified with a pathogenic variant in <i>HNRNPU</i> [<a class="bibr" href="#hnrnpu-ndd.REF.caliebe.2010.179" rid="hnrnpu-ndd.REF.caliebe.2010.179">Caliebe et al 2010</a>, <a class="bibr" href="#hnrnpu-ndd.REF.need.2012.353" rid="hnrnpu-ndd.REF.need.2012.353">Need et al 2012</a>, <a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al 2012</a>, <a class="bibr" href="#hnrnpu-ndd.REF.allen.2013.217" rid="hnrnpu-ndd.REF.allen.2013.217">Allen et al 2013</a>, <a class="bibr" href="#hnrnpu-ndd.REF.de_kovel.2016.568" rid="hnrnpu-ndd.REF.de_kovel.2016.568">de Kovel et al 2016</a>, <a class="bibr" href="#hnrnpu-ndd.REF.bramswig.2017.821" rid="hnrnpu-ndd.REF.bramswig.2017.821">Bramswig et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.depienne.2017.463" rid="hnrnpu-ndd.REF.depienne.2017.463">Depienne et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.leduc.2017.2680" rid="hnrnpu-ndd.REF.leduc.2017.2680">Leduc et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.yates.2017.3003" rid="hnrnpu-ndd.REF.yates.2017.3003">Yates et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>, <a class="bibr" href="#hnrnpu-ndd.REF.song.2021.663" rid="hnrnpu-ndd.REF.song.2021.663">Song et al 2021</a>, <a class="bibr" href="#hnrnpu-ndd.REF.taylor.2022.1497" rid="hnrnpu-ndd.REF.taylor.2022.1497">Taylor et al 2022</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddTselectfeaturesofhnrnpure"><a href="/books/NBK578573/table/hnrnpu-ndd.T.select_features_of_hnrnpure/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobhnrnpunddTselectfeaturesofhnrnpure"><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="hnrnpu-ndd.T.select_features_of_hnrnpure"><a href="/books/NBK578573/table/hnrnpu-ndd.T.select_features_of_hnrnpure/?report=objectonly" target="object" rid-ob="figobhnrnpunddTselectfeaturesofhnrnpure">Table 2. </a></h4><p class="float-caption no_bottom_margin">Select Features of <i>HNRNPU</i>-Related Neurodevelopmental Disorder </p></div></div><p><b>Developmental delay (DD) and intellectual disability (ID),</b> typically affecting all developmental domains and falling into the moderate-to-severe range, have been found in all reported individuals to date.</p><ul><li class="half_rhythm"><div>Speech delay is common and most reported individuals are nonverbal, although ascertainment bias against more mildly affected individuals may have skewed this finding to the more severe end of the <i>HNRNPU</i>-related neurodevelopmental disorder (<i>HNRNPU</i>-NDD) spectrum.</div></li><li class="half_rhythm"><div>Limited speech and ability to speak in short sentences has been described in some individuals.</div></li><li class="half_rhythm"><div>To date, most individuals have required special educational provisions, although children with <i>HNRNPU</i>-NDD may be able to attend a mainstream school with dedicated support.</div></li><li class="half_rhythm"><div>The vast majority of reported adults have required assisted living, which has allowed them some degree of independence.</div></li></ul><p>
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<b>Other neurodevelopmental features</b>
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</p><ul><li class="half_rhythm"><div><b>Hypotonia</b> is a common feature seen in about 80% of individuals with <i>HNRNPU</i>-NDD, especially during the neonatal period and in early infancy, and may persist into later childhood and adulthood. With time, some individuals may develop hypertonia leading to spasticity.</div></li><li class="half_rhythm"><div><b>Infant feeding difficulties</b> are observed in about 58% of affected individuals. The severity of feeding difficulties varies considerably and could be attributed to a combination of gastroesophageal reflux, hypotonia, and oromotor dysfunction, with some children requiring long-term gastrostomy tube insertion, while in others feeding may be improved with the use of temporary nasogastric tube feeding.</div></li><li class="half_rhythm"><div><b>Seizures</b> are seen in around 95% of reported individuals, with more than 90% presenting with their first seizure before age 24 months.</div><ul><li class="half_rhythm"><div>About 60% of individuals have generalized tonic-clonic seizures; 44% have absence seizures.</div></li><li class="half_rhythm"><div>Rarer types of seizures have included the following: two individuals with West syndrome [<a class="bibr" href="#hnrnpu-ndd.REF.bramswig.2017.821" rid="hnrnpu-ndd.REF.bramswig.2017.821">Bramswig et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.leduc.2017.2680" rid="hnrnpu-ndd.REF.leduc.2017.2680">Leduc et al 2017</a>]; one individual with Lennox-Gastaut syndrome [<a class="bibr" href="#hnrnpu-ndd.REF.leduc.2017.2680" rid="hnrnpu-ndd.REF.leduc.2017.2680">Leduc et al 2017</a>]; and one individual with Doose syndrome [<a class="bibr" href="#hnrnpu-ndd.REF.hinokuma.2020.442" rid="hnrnpu-ndd.REF.hinokuma.2020.442">Hinokuma et al 2020</a>].</div></li><li class="half_rhythm"><div>Most affected individuals have seizures as a presenting feature along with developmental delay.</div></li><li class="half_rhythm"><div>Seizures often respond to standard anti-seizure medication, although some may require more than one anti-seizure medication or a trial of such medications to attain reasonable seizure control.</div></li><li class="half_rhythm"><div>Ketogenic diet and newer medications to control seizures have been trialed (see <a href="#hnrnpu-ndd.Management">Management</a>).</div></li></ul></li><li class="half_rhythm"><div><b>Sleep</b>
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<b>disturbance</b> is a common finding, with some affected individuals reported to have sleep apnea, warranting a sleep study and further evaluation to establish a cause.</div></li></ul><p><b>Respiratory abnormalities.</b> Some affected individuals have abnormal breathing patterns. At least two have been reported with hyperventilation and apnea [<a class="bibr" href="#hnrnpu-ndd.REF.shimada.2018.813" rid="hnrnpu-ndd.REF.shimada.2018.813">Shimada et al 2018</a>, <a class="bibr" href="#hnrnpu-ndd.REF.spagnoli.2021.101" rid="hnrnpu-ndd.REF.spagnoli.2021.101">Spagnoli et al 2021</a>]. Other findings have included breath-holding episodes and irregular breathing patterns (particularly at night) that coincide with sleep disturbances.</p><p><b>Behavioral issues.</b> More than half of affected individuals have significant behavioral, social, and communication difficulties with substantial impact on the individuals and their families.</p><ul><li class="half_rhythm"><div>About one third meet the formal clinical diagnostic criteria of an autism spectrum disorder, whereas others have autistic-like features.</div></li><li class="half_rhythm"><div>In contrast, some are described as having a very friendly, placid personality.</div></li><li class="half_rhythm"><div>Less common behavioral phenotypes included obsessive-compulsive disorder and self-stimulatory behaviors.</div></li><li class="half_rhythm"><div>Other associated behaviors (more rarely seen):</div><ul><li class="half_rhythm"><div>Aggressive or destructive behavior</div></li><li class="half_rhythm"><div>Hand flapping</div></li><li class="half_rhythm"><div>Agitation</div></li><li class="half_rhythm"><div>Hyperventilation episodes (See also <b>Respiratory</b>
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<b>abnormalities</b>.)</div></li><li class="half_rhythm"><div>Attention-deficit disorder</div></li></ul></li></ul><p><b>Dysmorphic features.</b> No dysmorphic features that are specific to <i>HNRNPU</i>-NDD have been observed. If present, dysmorphic features are nonspecific. Features described in the literature include the following:</p><ul><li class="half_rhythm"><div>Abnormal head shape (frontal bossing, microcephaly, dolichocephaly)</div></li><li class="half_rhythm"><div>Prominent forehead</div></li><li class="half_rhythm"><div>Highly arched, thin eyebrows</div></li><li class="half_rhythm"><div>Palpebral fissure abnormalities (both upslanted and downslanted)</div></li><li class="half_rhythm"><div>Epicanthus</div></li><li class="half_rhythm"><div>Thin vermilion of the upper lip</div></li><li class="half_rhythm"><div>Low-hanging columella</div></li><li class="half_rhythm"><div>Widely spaced teeth</div></li></ul><p><b>Growth.</b> Proportionate short stature has been observed in about 50% of individuals for whom data have been reported; further studies are required to determine the cause. One individual had microcephaly.</p><p><b>Cardiac issues.</b> Nineteen individuals with cardiac abnormalities have been described. The following have been reported, in order from most to least frequent:</p><ul><li class="half_rhythm"><div>Atrial septal defect</div></li><li class="half_rhythm"><div>Ventricular septal defect</div></li><li class="half_rhythm"><div>Patent ductus arteriosus</div></li><li class="half_rhythm"><div>Tricuspid atresia, tetralogy of Fallot, aortic dilatation, and transposition of the great arteries together in one affected individual</div></li></ul><p><b>Eyes.</b> About 30% of affected individuals have strabismus. Hypermetropia has been described in at least two individuals.</p><p><b>Abnormalities of genitalia.</b> Undescended testis is reported in approximately 20% of affected males.</p><p><b>Neuroimaging.</b> There do not appear to be uniform findings on brain imaging in affected individuals that would specifically suggest this diagnosis; similarly, a normal brain MRI would not preclude this as a diagnosis.</p><ul><li class="half_rhythm"><div>Of 62 individuals reported in the literature who had a brain MRI imaging, 38 (61%) had abnormalities noted.</div></li><li class="half_rhythm"><div>The most common abnormality was ventriculomegaly, followed by thinning of the corpus callosum.</div></li></ul><p><b>Other associated features,</b> seen in fewer than 10% of individuals:</p><ul><li class="half_rhythm"><div><b>Hearing loss.</b> Two individuals with <i>HNRNPU</i>-NDD and sensorineural hearing impairment have been reported.</div></li><li class="half_rhythm"><div><b>Renal abnormalities.</b> Anatomic renal abnormalities are more likely to be seen in individuals with 1q44 deletion (see <a href="#hnrnpu-ndd.Genetically_Related_Allelic_D">Genetically Related Disorders</a>). About 8% of individuals with <i>HNRNPU</i>-NDD have renal issues including agenesis of the kidney, unilateral multicystic kidney, and renal pelvic ectasia.</div></li><li class="half_rhythm"><div><b>Musculoskeletal features</b> are rare [<a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al 2012</a>, <a class="bibr" href="#hnrnpu-ndd.REF.depienne.2017.463" rid="hnrnpu-ndd.REF.depienne.2017.463">Depienne et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.leduc.2017.2680" rid="hnrnpu-ndd.REF.leduc.2017.2680">Leduc et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>]:</div><ul><li class="half_rhythm"><div>Joint hyperlaxity (in 8 individuals)</div></li><li class="half_rhythm"><div>Butterfly vertebrae (1 individual) and scoliosis (3 individuals)</div></li><li class="half_rhythm"><div>Polydactyly, including bilateral postaxial polydactyly of the hand (1 individual) and preaxial polydactyly of the right foot (3 individuals)</div></li><li class="half_rhythm"><div>Cutaneous syndactyly of fingers 2 and 3</div></li><li class="half_rhythm"><div>Fifth digit clinodactyly</div></li><li class="half_rhythm"><div>Hallux valgus</div></li></ul></li></ul><p><b>Prognosis.</b> It is unknown whether life span in <i>HNRNPU</i>-NDD is abnormal. Based on current data, life span is not significantly limited by this condition, as several adults have been reported. Data on possible progression of behavior abnormalities or neurologic findings are still emerging. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.</p></div><div id="hnrnpu-ndd.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been identified.</p></div><div id="hnrnpu-ndd.Prevalence"><h3>Prevalence</h3><p>The prevalence of this condition is unknown. To date, approximately 83 individuals with <i>HNRNPU</i>-NDD have been reported.</p></div></div><div id="hnrnpu-ndd.Genetically_Related_Allelic_D"><h2 id="_hnrnpu-ndd_Genetically_Related_Allelic_D_">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>HNRNPU</i>.</p><p><b>Chromosome 1q44 deletion.</b> Individuals with larger deletions of 1q44 that include <i>HNRNPU</i> and adjacent genes have been described with a phenotype of severe developmental delay (particularly affecting speech development), microcephaly, hypogenesis/agenesis of the corpus callosum, and seizures. Renal abnormalities, strabismus, and hypotonia are more commonly described in individuals with a larger deletion that includes <i>HNRNPU</i> and adjacent genes. Upslanted palpebral fissures, widely spaced eyes, telecanthus, thin vermilion border of the lip, and exaggerated Cupid's bow are facial features described in individuals with deletion of this chromosomal region. Analysis of the smallest region of overlap identified <i>HNRNPU</i> as a candidate gene for the epilepsy and intellectual disability (ID) phenotype associated with this deletion [<a class="bibr" href="#hnrnpu-ndd.REF.caliebe.2010.179" rid="hnrnpu-ndd.REF.caliebe.2010.179">Caliebe et al 2010</a>, <a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al 2012</a>]. <a class="bibr" href="#hnrnpu-ndd.REF.depienne.2017.463" rid="hnrnpu-ndd.REF.depienne.2017.463">Depienne et al [2017]</a> showed that deletions of the 1q43q44 region that include <i>HNRNPU</i> determined the epilepsy phenotype in those with the 1q44 deletion syndrome, and had a significant influence on the degree of ID.</p></div><div id="hnrnpu-ndd.Differential_Diagnosis"><h2 id="_hnrnpu-ndd_Differential_Diagnosis_">Differential Diagnosis</h2><p>Because the phenotypic features associated with <i>HNRNPU</i>-related neurodevelopmental disorder are not sufficient to diagnose this condition, all disorders with epileptic encephalopathy and intellectual disability without other distinctive findings should be considered in the differential diagnosis. See <a href="https://omim.org/phenotypicSeries/PS308350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM Developmental and Epileptic Encephalopathy Phenotypic Series</a>.</p></div><div id="hnrnpu-ndd.Management"><h2 id="_hnrnpu-ndd_Management_">Management</h2><p>No clinical practice guidelines for <i>HNRNPU</i>-related neurodevelopmental disorder (<i>HNRNPU</i>-NDD) have been published.</p><div id="hnrnpu-ndd.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>HNRNPU</i>-NDD, the evaluations summarized in <a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobhnrnpunddTrecommendedevaluationsfol">Table 3</a> (if not performed as part of the evaluation that led to diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddTrecommendedevaluationsfol"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_evaluations_fol/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobhnrnpunddTrecommendedevaluationsfol"><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="hnrnpu-ndd.T.recommended_evaluations_fol"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobhnrnpunddTrecommendedevaluationsfol">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder </p></div></div></div><div id="hnrnpu-ndd.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddTtreatmentofmanifestations"><a href="/books/NBK578573/table/hnrnpu-ndd.T.treatment_of_manifestations/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobhnrnpunddTtreatmentofmanifestations"><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="hnrnpu-ndd.T.treatment_of_manifestations"><a href="/books/NBK578573/table/hnrnpu-ndd.T.treatment_of_manifestations/?report=objectonly" target="object" rid-ob="figobhnrnpunddTtreatmentofmanifestations">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder </p></div></div><div id="hnrnpu-ndd.Developmental_Delay__Intellec"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="hnrnpu-ndd.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
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<b>Gross motor dysfunction</b>
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</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li><li class="half_rhythm"><div>For muscle tone abnormalities including hypertonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox<sup>®</sup>, or orthopedic procedures.</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction</b> should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.</p></div><div id="hnrnpu-ndd.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.</p><p>Very occasionally, individuals with a <i>HNRNPU</i>-NDD have aggressive outbursts and may need further evaluation. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="hnrnpu-ndd.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddTrecommendedsurveillancefo"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_surveillance_fo/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobhnrnpunddTrecommendedsurveillancefo"><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="hnrnpu-ndd.T.recommended_surveillance_fo"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_surveillance_fo/?report=objectonly" target="object" rid-ob="figobhnrnpunddTrecommendedsurveillancefo">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder </p></div></div></div><div id="hnrnpu-ndd.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid activities and agents that may induce seizures, as the majority of affected individuals have a seizure disorder.</p></div><div id="hnrnpu-ndd.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#hnrnpu-ndd.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="hnrnpu-ndd.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Sustained single-dose gene therapy treatments for genetic forms of epilepsy, including <i>HNRNPU</i>-NDD, are currently being explored. This approach will be based on developing mRNA therapies and/or using a viral vector, such as AAV-9 (adeno-associated vector serotype 9), to deliver therapeutic protein to treat those forms of epilepsy caused by haploinsufficiency of proteins such as HNRNPU.</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="hnrnpu-ndd.Genetic_Counseling"><h2 id="_hnrnpu-ndd_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="hnrnpu-ndd.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>HNRNPU</i>-related neurodevelopmental disorder (<i>HNRNPU</i>-NDD) is an autosomal dominant disorder typically caused by a <i>de novo</i> pathogenic variant.</p></div><div id="hnrnpu-ndd.Risk_to_Family_Members"><h3>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>Most probands reported to date with <i>HNRNPU</i>-NDD whose parents have undergone molecular genetic testing have the disorder as the result of a <i>de novo</i>
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<i>HNRNPU</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.</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. Presumed parental mosaicism has been reported in one family with two affected sibs [<a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>].</div><div class="half_rhythm">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 cells only.</div></li></ul></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: if the <i>HNRNPU</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="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>].</p><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Each child of an individual with <i>HNRNPU</i>-NDD has a 50% chance of inheriting the <i>HNRNPU</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Individuals with <i>HNRNPU</i>-NDD are not known to have reproduced; however, many are not yet of reproductive age.</div></li></ul><p><b>Other family members.</b> Given that most probands with <i>HNRNPU</i>-NDD have the disorder as the result of a <i>de novo</i>
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<i>HNRNPU</i> pathogenic variant, the risk to other family members is presumed to be low.</p></div><div id="hnrnpu-ndd.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><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 parents of affected individuals.</div></li></ul></div><div id="hnrnpu-ndd.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Risk to future pregnancies is presumed to be low as the proband most likely has a <i>de novo HNRNPU</i> pathogenic variant. There is, however, a recurrence risk to sibs based on the possibility of parental germline mosaicism [<a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>]. Given this risk, prenatal and preimplantation genetic testing may be considered.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="hnrnpu-ndd.Resources"><h2 id="_hnrnpu-ndd_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>American Epilepsy Society</b>
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</div><div>
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<a href="https://www.aesnet.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aesnet.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Canadian Epilepsy Alliance</b>
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</div><div>Canada</div><div><b>Phone:</b> 1-866-EPILEPSY (1-866-374-5377)</div><div>
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<a href="https://www.canadianepilepsyalliance.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">canadianepilepsyalliance.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Epilepsy Foundation</b>
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</div><div><b>Phone:</b> 800-332-1000; 866-748-8008</div><div>
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<a href="https://www.epilepsy.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
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</div><div><b>Phone:</b> 800-352-9424</div><div>
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<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Epilepsy-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy and Seizures</a>
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</div></li><li class="half_rhythm"><div>
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<b>Unique: Understanding Rare Chromosome and Gene Disorders</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> +44 (0) 1883 723356</div><div><b>Email:</b> info@rarechromo.org</div><div>
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<a href="http://www.rarechromo.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rarechromo.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Simons Searchlight Registry</b>
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</div><div>
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<i>Simons Searchlight aims to further the understanding of rare genetic neurodevelopmental disorders.</i>
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</div><div><b>Phone:</b> 855-329-5638</div><div><b>Fax:</b> 570-214-7327</div><div><b>Email:</b> coordinator@simonssearchlight.org</div><div>
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<a href="https://www.simonssearchlight.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">simonssearchlight.org</a>
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</div></li></ul>
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</div><div id="hnrnpu-ndd.Molecular_Genetics"><h2 id="_hnrnpu-ndd_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="fighnrnpunddmolgenTA"><a href="/books/NBK578573/table/hnrnpu-ndd.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobhnrnpunddmolgenTA"><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="hnrnpu-ndd.molgen.TA"><a href="/books/NBK578573/table/hnrnpu-ndd.molgen.TA/?report=objectonly" target="object" rid-ob="figobhnrnpunddmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">HNRNPU-Related Neurodevelopmental Disorder: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighnrnpunddmolgenTB"><a href="/books/NBK578573/table/hnrnpu-ndd.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobhnrnpunddmolgenTB"><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="hnrnpu-ndd.molgen.TB"><a href="/books/NBK578573/table/hnrnpu-ndd.molgen.TB/?report=objectonly" target="object" rid-ob="figobhnrnpunddmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for HNRNPU-Related Neurodevelopmental Disorder (View All in OMIM) </p></div></div><div id="hnrnpu-ndd.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>HNRNPU</i>, located on 1q44, encodes for HNRNPU, which is a DNA- and RNA-binding protein. It is involved in nuclear chromatin organization, telomere-length regulation, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing, and mitotic cell cycle regulation. Additionally, it negatively regulates glucocorticoid-mediated transcriptional activation and participates in circadian regulation [<a class="bibr" href="#hnrnpu-ndd.REF.hasegawa.2010.469" rid="hnrnpu-ndd.REF.hasegawa.2010.469">Hasegawa et al 2010</a>, <a class="bibr" href="#hnrnpu-ndd.REF.bi.2013.4899" rid="hnrnpu-ndd.REF.bi.2013.4899">Bi et al 2013</a>, <a class="bibr" href="#hnrnpu-ndd.REF.nozawa.2017.1214" rid="hnrnpu-ndd.REF.nozawa.2017.1214">Nozawa et al 2017</a>, <a class="bibr" href="#hnrnpu-ndd.REF.havrilla.2019.88" rid="hnrnpu-ndd.REF.havrilla.2019.88">Havrilla et al 2019</a>]. <a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al [2012]</a> showed that HNRNPU is expressed in at least six different tissues: adult brain, heart, kidney, liver, cerebellum, and fetal brain, with the strongest expression in the cerebellum.</p><p><i>De novo</i> loss-of-function variants in <i>HNRNPU</i> can lead to a disease phenotype characterized by a variable neurodevelopmental syndrome with moderate-to-severe intellectual disability, seizures, behavioral abnormalities, and agenesis of the corpus callosum. A study by <a class="bibr" href="#hnrnpu-ndd.REF.leduc.2017.2680" rid="hnrnpu-ndd.REF.leduc.2017.2680">Leduc et al [2017]</a> in which whole-exome sequencing was used suggested that haploinsufficiency was the main mechanism of pathogenicity.</p><p><b>Mechanism of disease causation.</b> Loss of function</p></div></div><div id="hnrnpu-ndd.Chapter_Notes"><h2 id="_hnrnpu-ndd_Chapter_Notes_">Chapter Notes</h2><div id="hnrnpu-ndd.Author_Notes"><h3>Author Notes</h3><p>In the area of pediatric dysmorphology / genomic medicine, Dr Balasubramanian has led several studies focused on genotype-phenotype correlation in newly identified genes from next-generation sequencing studies such as the Deciphering Developmental Disorders (DDD) study, and has several first/senior author articles published in this area on large cohorts of individuals with new syndromal diagnoses. Her research is now focused on exploring disease mechanisms and establishing international registries for these disorders to better understand the natural history of these conditions. Dr Balasubramanian has published the largest cohort of people so far with <i>HNRNPU</i>-related neurodevelopmental disorder and has gathered phenotypic data on more than 50 individuals with <i>HNRNPU</i>-related neurodevelopmental disorder. She has also written the Unique patient support group information leaflet on the condition along with Anna Pelling from Unique (<a href="https://rarechromo.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rarechromo.org</a>).</p><p>Dr Balasubramanian's web pages: <a href="https://www.sheffield.ac.uk/medicine/people/oncology-metabolism/meena-balasubramanian" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.sheffield.ac.uk</a> and <a href="https://mellanbycentre.org/meena-balasubramanian/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.mellanbycentre.org</a></p></div><div id="hnrnpu-ndd.Acknowledgments"><h3>Acknowledgments</h3><p>Dr Balasubramanian would like to thank all the families and their clinicians who have so far contributed to ongoing <i>HNRNPU</i> research, and the <i>HNRNPU</i>-related neurodevelopmental disorder patient support group for all their help and contribution in understanding more about the natural history of this condition. Dr Balasubramanian would also like to thank and acknowledge trainees in Dr Balasubramanian's group: Michael Yates, Anna Durkin, and James Taylor, who have contributed to the medical literature on <i>HNRNPU</i>.</p></div><div id="hnrnpu-ndd.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>10 March 2022 (ma) Review posted live</div></li><li class="half_rhythm"><div>22 September 2021 (mb) Original submission</div></li></ul></div></div><div id="hnrnpu-ndd.References"><h2 id="_hnrnpu-ndd_References_">References</h2><div id="hnrnpu-ndd.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="hnrnpu-ndd.REF.allen.2013.217">Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR, et al. 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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>Balasubramanian M. HNRNPU-Related Neurodevelopmental Disorder. 2022 Mar 10. 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/hnrnph2-ndd/?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/hoxa1-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="figobhnrnpunddTmoleculargenetictestingu"><div id="hnrnpu-ndd.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>HNRNPU</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_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_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2, 3</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HNRNPU</i>
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</td><td headers="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></td><td headers="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">98% <sup>5</sup></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></td><td headers="hd_h_hnrnpu-ndd.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2% <sup>7</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="hnrnpu-ndd.TF.1.1"><p class="no_margin">See <a href="/books/NBK578573/?report=reader#hnrnpu-ndd.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="hnrnpu-ndd.TF.1.2"><p class="no_margin">See <a href="#hnrnpu-ndd.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hnrnpu-ndd.TF.1.3"><p class="no_margin">Three additional individuals with contiguous gene deletions or duplications (not included in these calculations) have been reported (see <a href="#hnrnpu-ndd.Genetically_Related_Allelic_D">Genetically Related Disorders</a>) [<a class="bibr" href="#hnrnpu-ndd.REF.caliebe.2010.179" rid="hnrnpu-ndd.REF.caliebe.2010.179">Caliebe et al 2010</a>, <a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al 2012</a>, <a class="bibr" href="#hnrnpu-ndd.REF.bramswig.2017.821" rid="hnrnpu-ndd.REF.bramswig.2017.821">Bramswig et al 2017</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hnrnpu-ndd.TF.1.4"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; 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>5. </dt><dd><div id="hnrnpu-ndd.TF.1.5"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#hnrnpu-ndd.REF.stenson.2020.1197" rid="hnrnpu-ndd.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="hnrnpu-ndd.TF.1.6"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. 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="#hnrnpu-ndd.REF.caliebe.2010.179" rid="hnrnpu-ndd.REF.caliebe.2010.179">Caliebe et al [2010]</a> and <a class="bibr" href="#hnrnpu-ndd.REF.thierry.2012.1633" rid="hnrnpu-ndd.REF.thierry.2012.1633">Thierry et al [2012]</a>) may not be detected by these methods.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="hnrnpu-ndd.TF.1.7"><p class="no_margin">One affected individual had deletion of the last three exons of <i>HNRNPU</i> [<a class="bibr" href="#hnrnpu-ndd.REF.durkin.2020.1637" rid="hnrnpu-ndd.REF.durkin.2020.1637">Durkin et al 2020</a>]. One affected individual has been identified with an <i>HNRNPU</i> deletion that includes exons 1-11 [<a class="bibr" href="#hnrnpu-ndd.REF.taylor.2022.1497" rid="hnrnpu-ndd.REF.taylor.2022.1497">Taylor et al 2022</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhnrnpunddTselectfeaturesofhnrnpure"><div id="hnrnpu-ndd.T.select_features_of_hnrnpure" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of <i>HNRNPU</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.T.select_features_of_hnrnpure/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.T.select_features_of_hnrnpure_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons<br />w/Feature</th><th id="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_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_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysmorphic craniofacial features</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <b>Dysmorphic features</b> following this table.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizure disorder</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">95%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~90% have 1st seizure before age 24 mos (tonic-clonic in ~60%, absence in ~44%) <sup>1</sup></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intellectual disability</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">84%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically moderate to severe</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech delay</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usually limited or no speech</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">79%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Slightly fewer than 50% have congenital hypotonia.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding difficulties</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">57%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Some require supplemental nasogastric feeding or percutaneous gastrostomy.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavioral issues</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Autistic features are observed in ~33% of affected persons.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eye anomalies</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The most common finding is strabismus.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac abnormalities</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Septal defects are the most common.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal anomalies</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><10%</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperventilation & apnea</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hnrnpu-ndd.T.select_features_of_hnrnpure_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>1. </dt><dd><div id="hnrnpu-ndd.TF.2.1"><p class="no_margin">Of note, some persons have both types of seizures, such that the combined percentages are more than 100%.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhnrnpunddTrecommendedevaluationsfol"><div id="hnrnpu-ndd.T.recommended_evaluations_fol" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_evaluations_fol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.T.recommended_evaluations_fol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_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_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Constitutional</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of growth parameters</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl weight, length/height, & head circumference</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl brain MRI if unresolved/refractory seizures are present</div></li><li class="half_rhythm"><div>Consider EEG if seizures are a concern.</div></li></ul>
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</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech/language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
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</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
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<br />
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<b>Behavioral</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For persons age >12 mos: screening for behavior concerns incl sleep disturbances, ADD, aggressive or destructive behaviors, &/or traits suggestive of ASD</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal/</b>
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<br />
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<b>Feeding</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of feeding ability & nutritional status</div></li><li class="half_rhythm"><div>Consider eval for swallowing dysfunction & gastric tube placement in those w/dysphagia or continued poor growth on oral feedings alone. <sup>1</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiovascular</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess valvular problems & anatomic heart defects</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory/</b>
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<br />
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<b>Sleep</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for signs & symptoms of sleep apnea</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider polysomnogram if concerns about sleep disturbance or apnea.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for strabismus</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for hearing loss</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genitourinary</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical exam for undescended testes in males</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to urologist, if present.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider renal ultrasound to assess for renal anomalies.</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In those w/unexplained hypertension &/or history of UTIs</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
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<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Mobility, ADL, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul>
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</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
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<br />
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<b>counseling</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>HNRNPU</i>-NDD to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_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>
|
|
<br />
|
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<b>& resources</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hnrnpu-ndd.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#hnrnpu-ndd.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</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">ADD = attention-deficit disorder; ADL = activities of daily living; ASD = autism spectrum disorder; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy; UTI = urinary tract infection</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hnrnpu-ndd.TF.3.1"><p class="no_margin">See also <b>Oral motor dysfunction</b> in <a href="#hnrnpu-ndd.Motor_Dysfunction">Treatment of Manifestations</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hnrnpu-ndd.TF.3.2"><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="figobhnrnpunddTtreatmentofmanifestations"><div id="hnrnpu-ndd.T.treatment_of_manifestations" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.T.treatment_of_manifestations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.T.treatment_of_manifestations_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_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_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypotonia/</b>
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<br />
|
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<b>Hypertonia</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT incl exercises to address muscle tone issues</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider need for positioning & mobility devices, disability parking placard.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider involving appropriate specialists to aid in mgmt of baclofen, tizanidine, Botox<sup>®</sup>, or orthopedic procedures.</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For those w/severe hypertonia</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Epilepsy</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; sodium valproate is the most commonly used & effective medication. <sup>1</sup></div></li><li class="half_rhythm"><div>Ketogenic diet & newer ASMs may be required for refractory seizures.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>2</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>DD/ID /</b>
|
|
<br />
|
|
<b>Behavioral</b>
|
|
<br />
|
|
<b>issues</b>
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|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#hnrnpu-ndd.Developmental_Delay__Intellec">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Poor weight</b>
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<br />
|
|
<b>gain / Failure</b>
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<br />
|
|
<b>to thrive</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding therapy; nasogastric or gastrostomy tube placement may be required for persistent feeding issues.</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Congenital</b>
|
|
<br />
|
|
<b>heart defects</b>
|
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</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per cardiologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sleep apnea</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In conjunction w/sleep specialist, appropriate treatment options may incl supplemental oxygen, CPAP, or BiPAP.</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">It is important to consider additional factors that may contribute to sleep apnea, incl opioids & ASM.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hyperventilation /</b>
|
|
<br />
|
|
<b>Abnormal</b>
|
|
<br />
|
|
<b>breathing</b>
|
|
<br />
|
|
<b>patterns</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per pulmonologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combined treatment w/acetazolamide, alprazolam, & aripiprazole successfully used in 1 person. <sup>3</sup></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Strabismus</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) per ophthalmologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing loss</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing aids may be helpful; per otolaryngologist.</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider community hearing services through early intervention or school district in severe cases.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Renal</b>
|
|
<br />
|
|
<b>anomalies</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per nephrologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Undescended</b>
|
|
<br />
|
|
<b>testes</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per urologist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Limb anomalies</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per orthopedist</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Family/</b>
|
|
<br />
|
|
<b>Community</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or Special Olympics.</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">ASM = anti-seizure medication; BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hnrnpu-ndd.TF.4.1"><p class="no_margin">For individuals on valproate and other ASMs, routine monitoring of liver function tests and observation for behavioral dysregulation should be considered.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hnrnpu-ndd.TF.4.2"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hnrnpu-ndd.TF.4.3"><p class="no_margin">
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<a class="bibr" href="#hnrnpu-ndd.REF.spagnoli.2021.101" rid="hnrnpu-ndd.REF.spagnoli.2021.101">Spagnoli et al [2021]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhnrnpunddTrecommendedsurveillancefo"><div id="hnrnpu-ndd.T.recommended_surveillance_fo" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>HNRNPU</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.T.recommended_surveillance_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.T.recommended_surveillance_fo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_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_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Growth/Feeding</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measurement of growth parameters</div></li><li class="half_rhythm"><div>Eval of nutritional status & safety of oral intake</div></li></ul>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_3" rowspan="8" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for constipation.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor those w/seizures as clinically indicated.</div></li><li class="half_rhythm"><div>Assess for new manifestations such as seizures & changes in tone.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Development</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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|
<b>Psychiatric/</b>
|
|
<br />
|
|
<b>Behavioral</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavioral assessment for anxiety, attention, & aggressive or self-injurious behavior</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Respiratory</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for evidence of hyperventilation & apnea.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical medicine, OT/PT assessment of mobility, self-help skills</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Family/</b>
|
|
<br />
|
|
<b>Community</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as clinically indicated</td></tr><tr><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_hnrnpu-ndd.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</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">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhnrnpunddmolgenTA"><div id="hnrnpu-ndd.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>HNRNPU-Related Neurodevelopmental Disorder: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578573/table/hnrnpu-ndd.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_hnrnpu-ndd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/3192" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>HNRNPU</i>
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</a>
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</td><td headers="hd_b_hnrnpu-ndd.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=3192" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1q44</a>
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</td><td headers="hd_b_hnrnpu-ndd.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/Q00839" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Heterogeneous nuclear ribonucleoprotein U</a>
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</td><td headers="hd_b_hnrnpu-ndd.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=HNRNPU" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HNRNPU</a>
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</td><td headers="hd_b_hnrnpu-ndd.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=HNRNPU[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HNRNPU</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="hnrnpu-ndd.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="figobhnrnpunddmolgenTB"><div id="hnrnpu-ndd.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for HNRNPU-Related Neurodevelopmental Disorder (<a href="/omim/602869,617391" 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/NBK578573/table/hnrnpu-ndd.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hnrnpu-ndd.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/602869" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">602869</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN U; HNRNPU</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/617391" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">617391</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 54; DEE54</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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