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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>NSDHL-Related Disorders - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="NSDHL-Related Disorders">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2024/09/05">
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<meta name="citation_author" content="Mazen Kurban">
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<meta name="citation_author" content="Jinia El Feghaly">
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<meta name="citation_author" content="Lamiaa Hamie">
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<meta name="citation_keywords" content="CHILD (Congenital Hemidysplasia with Ichthyosiform Nevus and Limb Defects) Syndrome">
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<meta name="citation_keywords" content="CK Syndrome">
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<meta name="citation_keywords" content="Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating">
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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="_NBK51754_"><span class="title" itemprop="name"><i>NSDHL</i>-Related Disorders</span></h1><p class="contribs">Kurban M, El Feghaly J, Hamie L.</p><p class="fm-aai"><a href="#_NBK51754_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 34 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="nsdhl-dis.Summary" itemprop="description"><h2 id="_nsdhl-dis_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>NSDHL</i>-related disorders include CHILD (<i>c</i>ongenital <i>h</i>emidysplasia with <i>i</i>chthyosiform nevus and <i>l</i>imb <i>d</i>efects) syndrome, an X-linked disorder that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males.</p><p>CHILD syndrome is characterized by unilateral distribution of ichthyosiform skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Onychodystrophy and periungual hyperkeratosis are common. Heart, lung, and kidney malformations can also occur.</p><p>CK syndrome is characterized by mild-to-severe cognitive impairment and behavior problems (aggression, attention-deficit/hyperactivity disorder [ADHD], and irritability). All reported affected males have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis. Strabismus is common. Optic atrophy is also reported.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of CHILD syndrome is established in a female proband with a heterozygous <i>NSDHL</i> pathogenic variant identified by molecular genetic testing that results in loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase, the protein encoded by <i>NSDHL</i>. The diagnosis of CK syndrome is established in a male proband with a hemizygous <i>NSDHL</i> hypomorphic pathogenic variant identified by molecular genetic testing that results in partial loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> In CHILD syndrome, no one therapy described to date appears to ameliorate the cutaneous findings for every reported individual. Oral and topical ketoconazole may reduce lesions. Topical statin treatment alone or combined with cholesterol and/or glycolic acid can be beneficial. Treatment of an inflammatory nevus by grafting skin obtained from a contralateral unaffected region has been successful. Lactic acid 12% creams or lotions can reduce itching, and urea skin creams can reduce dryness. Scoliosis and joint contractures are treated with braces and/or corrective surgery. Standard management for heart, lung, kidney, and gastrointestinal manifestations.</p><p>In CK syndrome, developmental and educational support; behavior modification and/or drug therapy to control aggression and help with manifestations of ADHD; anti-seizure medication to control seizures; standard treatments for orthopedic and ocular manifestations; support transition to adult care; and social work and family support as needed.</p><p><i>Surveillance:</i> In CHILD syndrome, monitor for new cutaneous lesions, musculoskeletal deformities such as scoliosis and joint contractures, and neurologic, cardiac, and/or kidney manifestations annually or as needed.</p><p>In CK syndrome, monitor for developmental and educational progress, behavioral issues, changes in seizures, and development of scoliosis and/or kyphosis annually or as needed. Follow-up ophthalmology examination per ophthalmologist.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>NSDHL</i>-related disorders are inherited in an X-linked manner. CHILD syndrome is usually male lethal during gestation and thus predominantly affects females. CK syndrome predominantly affects males.</p><p><i>CHILD syndrome:</i> If the mother of a proband has an <i>NSDHL</i> pathogenic variant, the chance of transmitting it in each pregnancy is 50%. However, since studies suggest that male conceptuses with an <i>NSDHL</i> pathogenic variant generally abort or resorb spontaneously, the expected live-born distribution is: 33% heterozygous (typically) affected females; 33% unaffected females; and 33% unaffected males.</p><p><i>CK syndrome:</i> If the mother of a proband is heterozygous for an <i>NSDHL</i> pathogenic variant, the expected chance of transmitting it in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygous and may have a range of behavioral problems. Identification of female heterozygotes requires prior identification of the <i>NSDHL</i> pathogenic variant in the family.</p><p>Once the <i>NSDHL</i> pathogenic variant has been identified in a family member with an <i>NSDHL</i>-related disorder, prenatal and preimplantation genetic testing are possible.</p></div></div><div id="nsdhl-dis.GeneReview_Scope"><h2 id="_nsdhl-dis_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTc"><a href="/books/NBK51754/table/nsdhl-dis.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobnsdhldisTc"><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="nsdhl-dis.Tc"><a href="/books/NBK51754/table/nsdhl-dis.Tc/?report=objectonly" target="object" rid-ob="figobnsdhldisTc">Table</a></h4><p class="float-caption no_bottom_margin">CHILD (<i>c</i>ongenital <i>h</i>emidysplasia with <i>i</i>chthyosiform nevus and <i>l</i>imb <i>d</i>efects) syndrome CK syndrome</p></div></div></div><div id="nsdhl-dis.Diagnosis"><h2 id="_nsdhl-dis_Diagnosis_">Diagnosis</h2><p>For the purposes of this <i>GeneReview</i>, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care [<a class="bibr" href="#nsdhl-dis.REF.caughey.2021.1953" rid="nsdhl-dis.REF.caughey.2021.1953">Caughey et al 2021</a>].</p><p>No consensus clinical diagnostic criteria for <i>NSDHL</i>-related disorders have been published.</p><div id="nsdhl-dis.Suggestive_Findings"><h3>Suggestive Findings</h3><p>An <i>NSDHL</i>-related disorder <b>should be suspected</b> in an individual with features of CHILD (<i>c</i>ongenital <i>h</i>emidysplasia with <i>i</i>chthyosiform nevus [also known as <i>i</i>chthyosiform erythroderma] and <i>l</i>imb <i>d</i>efects) syndrome (typically in females) or CK syndrome (intellectual disability and associated features in males) as follows.</p><p>
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<b>CHILD syndrome</b>
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</p><ul><li class="half_rhythm"><div>Unilateral distribution of ichthyosiform nevus</div></li><li class="half_rhythm"><div>Limb defects ipsilateral to the skin lesions</div></li><li class="half_rhythm"><div>Punctate calcifications of cartilaginous structures</div></li><li class="half_rhythm"><div>Central nervous system (CNS) anomalies</div></li><li class="half_rhythm"><div>Visceral malformations (heart, lung, and/or renal anomalies)</div></li></ul><p><b>CK syndrome</b> [<a class="bibr" href="#nsdhl-dis.REF.du_souich.2009.2469" rid="nsdhl-dis.REF.du_souich.2009.2469">du Souich et al 2009</a>, <a class="bibr" href="#nsdhl-dis.REF.mclarren.2010.905" rid="nsdhl-dis.REF.mclarren.2010.905">McLarren et al 2010</a>, <a class="bibr" href="#nsdhl-dis.REF.preiksaitiene.2015.1342" rid="nsdhl-dis.REF.preiksaitiene.2015.1342">Preiksaitiene et al 2015</a>]</p><ul><li class="half_rhythm"><div>CNS findings, including mild-to-severe intellectual disability, microcephaly, seizures, cerebral cortical malformations (polymicrogyria), and spasticity</div></li><li class="half_rhythm"><div>Characteristic craniofacial features, such as microcephaly, plagiocephaly, almond-shaped and upslanted palpebral fissures, prominent nasal bridge, high-arched palate, crowded dentition, and micrognathia</div></li><li class="half_rhythm"><div>Thin body habitus with normal height</div></li></ul></div><div id="nsdhl-dis.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Female proband.</b> The diagnosis of CHILD syndrome <b>is established</b> in a female proband with a heterozygous <i>NSDHL</i> pathogenic (or likely pathogenic) variant identified by molecular genetic testing that results in loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase, the protein encoded by <i>NSDHL</i> (see <a href="/books/NBK51754/table/nsdhl-dis.T.molecular_genetic_testing_us/?report=objectonly" target="object" rid-ob="figobnsdhldisTmoleculargenetictestingus">Table 1</a>). Note: CHILD syndrome is usually male lethal during gestation, although it has been reported in a few males and has been attributed to postzygotic mosaicism.</p><p><b>Male proband.</b> The diagnosis of CK syndrome <b>is established</b> in a male proband with a hemizygous <i>NSDHL</i> hypomorphic pathogenic (or likely pathogenic) variant identified by molecular genetic testing that results in partial loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase (see <a href="/books/NBK51754/table/nsdhl-dis.T.molecular_genetic_testing_us/?report=objectonly" target="object" rid-ob="figobnsdhldisTmoleculargenetictestingus">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#nsdhl-dis.REF.richards.2015.405" rid="nsdhl-dis.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of a heterozygous or hemizygous <i>NSDHL</i> variant of uncertain significance does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#nsdhl-dis.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#nsdhl-dis.Option_2">Option 2</a>).</p><div id="nsdhl-dis.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of an <i>NSDHL-</i>related disorder, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>NSDHL</i> is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>NSDHL</i> and other genes of interest (see <a href="#nsdhl-dis.Differential_Diagnosis">Differential Diagnosis</a>) may be considered to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</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></ul></div><div id="nsdhl-dis.Option_2"><h4>Option 2</h4><p>When the diagnosis of an <i>NSDHL-</i>related disorder has not been considered because an individual has atypical phenotypic features, <b>comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTmoleculargenetictestingus"><a href="/books/NBK51754/table/nsdhl-dis.T.molecular_genetic_testing_us/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobnsdhldisTmoleculargenetictestingus"><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="nsdhl-dis.T.molecular_genetic_testing_us"><a href="/books/NBK51754/table/nsdhl-dis.T.molecular_genetic_testing_us/?report=objectonly" target="object" rid-ob="figobnsdhldisTmoleculargenetictestingus">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>NSDHL</i>-Related Disorders </p></div></div><p>
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<b>Analyte testing in CHILD syndrome and CK syndrome</b>
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</p><ul><li class="half_rhythm"><div>When cultured in cholesterol-depleted medium, lymphoblastoid cells of individuals with CHILD syndrome and CK syndrome have increased levels of methyl- and carboxysterols and slightly decreased levels of cholesterol [<a class="bibr" href="#nsdhl-dis.REF.mclarren.2010.905" rid="nsdhl-dis.REF.mclarren.2010.905">McLarren et al 2010</a>].</div></li><li class="half_rhythm"><div>In individuals with CHILD syndrome, sterol analysis of skin flakes collected from an affected area show elevated levels of methyl- and carboxysterols [<a class="bibr" href="#nsdhl-dis.REF.maceda.2020.e236859" rid="nsdhl-dis.REF.maceda.2020.e236859">Maceda et al 2020</a>].</div></li><li class="half_rhythm"><div>Serum concentrations of methylsterol and cholesterol are almost always normal in individuals with CHILD syndrome and CK syndrome. Two ketosterols were detected in one female with CHILD syndrome [<a class="bibr" href="#nsdhl-dis.REF.maceda.2020.e236859" rid="nsdhl-dis.REF.maceda.2020.e236859">Maceda et al 2020</a>].</div></li></ul></div></div></div><div id="nsdhl-dis.Clinical_Characteristics"><h2 id="_nsdhl-dis_Clinical_Characteristics_">Clinical Characteristics</h2><div id="nsdhl-dis.Clinical_Description"><h3>Clinical Description</h3><p><i>NSDHL</i>-related disorders include CHILD (<i>c</i>ongenital <i>h</i>emidysplasia with <i>i</i>chthyosiform nevus and <i>l</i>imb <i>d</i>efects) syndrome, an X-linked disorder that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males.</p><div id="nsdhl-dis.CHILD_Syndrome"><h4>CHILD Syndrome</h4><p>CHILD syndrome is characterized by unilateral ichthyosiform skin lesions typically with sharp midline demarcation with ipsilateral limb defects, onychodystrophy, and periungual hyperkeratosis (see <a class="figpopup" href="/books/NBK51754/figure/nsdhl-dis.F1/?report=objectonly" target="object" rid-figpopup="fignsdhldisF1" rid-ob="figobnsdhldisF1">Figure 1</a>). Some individuals have scoliosis, joint contractures, central nervous system (CNS) anomalies, and congenital heart defects. CHILD syndrome predominantly affects females and is usually male lethal during gestation. To date, more than 60 individuals have been reported with CHILD syndrome.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="fignsdhldisF1" co-legend-rid="figlgndnsdhldisF1"><a href="/books/NBK51754/figure/nsdhl-dis.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="fignsdhldisF1" rid-ob="figobnsdhldisF1"><img class="small-thumb" src="/books/NBK51754/bin/nsdhl-dis-Image001.gif" src-large="/books/NBK51754/bin/nsdhl-dis-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndnsdhldisF1"><h4 id="nsdhl-dis.F1"><a href="/books/NBK51754/figure/nsdhl-dis.F1/?report=objectonly" target="object" rid-ob="figobnsdhldisF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Photographs of a female with CHILD syndrome A. Upper left limb. Note the forearm hypoplasia, ectrodactyly, onychodystrophy, and characteristic ichthyosiform skin lesions with yellow scales.</p></div></div><p>
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<b>Dermatologic findings</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Ichthyosiform nevus (or erythroderma).</b> Cutaneous lesions are characterized by ichthyosiform inflammatory erythematous skin plaques with yellowish and waxy adherent scales and a sharp demarcation at the midline of the body. Lesions can be patchy or continuous. In some individuals, islands of normal skin are apparent within the lesion. Lesions can follow the lines of Blaschko. The skin lesions are right-sided in about two thirds of individuals but can be left-sided or bilateral [<a class="bibr" href="#nsdhl-dis.REF.k_nig.2002.594" rid="nsdhl-dis.REF.k_nig.2002.594">König et al 2002</a>, <a class="bibr" href="#nsdhl-dis.REF.hummel.2003.246" rid="nsdhl-dis.REF.hummel.2003.246">Hummel et al 2003</a>, <a class="bibr" href="#nsdhl-dis.REF.mi.2015.e277" rid="nsdhl-dis.REF.mi.2015.e277">Mi et al 2015</a>]. The ichthyosiform skin lesions are evident at birth or in the first weeks to few months of life; new lesions may develop in later life. The face is usually spared but can be involved in some individuals. Ipsilateral scalp alopecia has been reported [<a class="bibr" href="#nsdhl-dis.REF.hummel.2003.246" rid="nsdhl-dis.REF.hummel.2003.246">Hummel et al 2003</a>, <a class="bibr" href="#nsdhl-dis.REF.avgerinou.2010.733" rid="nsdhl-dis.REF.avgerinou.2010.733">Avgerinou et al 2010</a>, <a class="bibr" href="#nsdhl-dis.REF.heda.2014.483" rid="nsdhl-dis.REF.heda.2014.483">Heda et al 2014</a>]. Most of the skin lesions improve spontaneously, but some can cause lifelong morbidity. Lesions in the intertriginous areas tend to be more persistent; this is termed ptychotropism [<a class="bibr" href="#nsdhl-dis.REF.happle.1990.763" rid="nsdhl-dis.REF.happle.1990.763">Happle 1990</a>]. Ichthyosiform skin lesions can develop after infancy at sites of injury such as a surgical wound.</div><div class="half_rhythm">Histologically, the skin lesions exhibit hyperkeratosis, parakeratosis, and acanthosis as well as inflammatory and lipid-laden infiltrates (foamy histiocytes) within the dermal papillae [<a class="bibr" href="#nsdhl-dis.REF.hebert.1987.503" rid="nsdhl-dis.REF.hebert.1987.503">Hebert et al 1987</a>, <a class="bibr" href="#nsdhl-dis.REF.hashimoto.1995.116" rid="nsdhl-dis.REF.hashimoto.1995.116">Hashimoto et al 1995</a>]. The latter phenomenon has been termed <b>verruciform xanthomas</b> (VX); this is a nonspecific histopathologic finding that can be seen in other entities but may help distinguish CHILD nevi from other psoriasiform lesions on histopathology. More recently, tympanoxyloid (drumstick-like) VX involving the distal digits have been reported as a likely more "pathognomonic" finding of CHILD syndrome [<a class="bibr" href="#nsdhl-dis.REF.juratli.2020.e70" rid="nsdhl-dis.REF.juratli.2020.e70">Juratli et al 2020</a>]. Verrucous lesions can also involve the mucosal surfaces [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>]. The skin lesions in persons with <i>NSDHL</i> pathogenic variants can be distinguished histologically and biochemically from those in individuals with <a href="/books/n/gene/x-dcdp/?report=reader">chondrodysplasia punctata 2, X-linked</a>.</div><div class="half_rhythm">Occasionally, heterozygous females present with comparatively minor skin lesions such as Blaschko-linear inflammatory scaly lesions, patchy alopecia, or nail changes. In some affected females, an ichthyosiform nevus (CHILD nevus) can be present without any additional manifestations of CHILD syndrome [<a class="bibr" href="#nsdhl-dis.REF.happle.1995.210" rid="nsdhl-dis.REF.happle.1995.210">Happle et al 1995</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Nails.</b> Onychodystrophy, onychorrhexis, and periungual hyperkeratosis are common. Claw-like nails can be seen.</div></li></ul><p>
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<b>Skeletal features</b>
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</p><ul><li class="half_rhythm"><div><b>Limbs.</b> Ipsilateral hypoplasia of the limbs varies from shortening of metacarpals and phalanges and sometimes other long bones (hypomelia) to absence of the entire limb (amelia). Joint contractures are reported. Oligodactyly can be seen; polydactyly and syndactyly have been rarely reported. The skeletal involvement is right-sided in around two thirds of individuals, but can be left-sided or, rarely, bilateral [<a class="bibr" href="#nsdhl-dis.REF.k_nig.2002.594" rid="nsdhl-dis.REF.k_nig.2002.594">König et al 2002</a>, <a class="bibr" href="#nsdhl-dis.REF.hummel.2003.246" rid="nsdhl-dis.REF.hummel.2003.246">Hummel et al 2003</a>, <a class="bibr" href="#nsdhl-dis.REF.mi.2015.e277" rid="nsdhl-dis.REF.mi.2015.e277">Mi et al 2015</a>, <a class="bibr" href="#nsdhl-dis.REF.rossi.2015.965" rid="nsdhl-dis.REF.rossi.2015.965">Rossi et al 2015</a>].</div></li><li class="half_rhythm"><div><b>Other musculoskeletal defects</b> (generally evident in infancy) include skeletal asymmetry and scoliosis. Incomplete development (hypoplasia) or absence of vertebrae, pelvis, ribs, mandible, and skull has also been reported [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>].</div></li><li class="half_rhythm"><div><b>Punctate calcifications of cartilaginous structures.</b> Unilateral punctate epiphyseal calcifications (chondrodysplasia punctata) in the pelvis, ribs, vertebrae, and extremities have been reported and are usually seen in the affected limb or body part. These can be visible on radiographs in infancy. In one child, the punctate calcifications were reported to have disappeared completely by age two years [<a class="bibr" href="#nsdhl-dis.REF.happle.1980.27" rid="nsdhl-dis.REF.happle.1980.27">Happle et al 1980</a>]; it is not known whether stippling always disappears. Ipsilateral stippling has also been observed in the sella turcica and the laryngeal, nasal, and thyroid cartilage [<a class="bibr" href="#nsdhl-dis.REF.happle.1980.27" rid="nsdhl-dis.REF.happle.1980.27">Happle et al 1980</a>, <a class="bibr" href="#nsdhl-dis.REF.grange.2000.328" rid="nsdhl-dis.REF.grange.2000.328">Grange et al 2000</a>].</div></li></ul><p>
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<b>Other structural anomalies</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>CNS anomalies</b> include unilateral hypoplasia or underdevelopment of the brain, lissencephaly type II, and cerebellar malformation [<a class="bibr" href="#nsdhl-dis.REF.schmidtsidor.2008.232" rid="nsdhl-dis.REF.schmidtsidor.2008.232">Schmidt-Sidor et al 2008</a>]. One individual had multiple left-sided brain anomalies as a consequence of disturbances in proliferation and migration [<a class="bibr" href="#nsdhl-dis.REF.schmidtsidor.2008.232" rid="nsdhl-dis.REF.schmidtsidor.2008.232">Schmidt-Sidor et al 2008</a>]. The Virchow-Robin spaces of the left parietal lobe were locally enlarged in one affected female [<a class="bibr" href="#nsdhl-dis.REF.yu.2018.1209" rid="nsdhl-dis.REF.yu.2018.1209">Yu et al 2018</a>].</div><div class="half_rhythm">Intellect is usually normal.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Heart defects</b> include septal defects [<a class="bibr" href="#nsdhl-dis.REF.k_nig.2002.594" rid="nsdhl-dis.REF.k_nig.2002.594">König et al 2002</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Lung hypoplasia</b> has been observed in several individuals [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>] and can cause respiratory compromise and death [<a class="bibr" href="#nsdhl-dis.REF.hummel.2003.246" rid="nsdhl-dis.REF.hummel.2003.246">Hummel et al 2003</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Renal manifestations</b> range from unilateral hydronephrosis to renal agenesis. The frequency of these is unknown.</div></li></ul><p><b>Other findings.</b> Reported additional findings include hearing loss, absence of facial muscles, and unilateral hypoplasia of the thyroid gland, adrenal glands, ovaries, and fallopian tubes [<a class="bibr" href="#nsdhl-dis.REF.happle.1980.27" rid="nsdhl-dis.REF.happle.1980.27">Happle et al 1980</a>, <a class="bibr" href="#nsdhl-dis.REF.k_nig.2002.594" rid="nsdhl-dis.REF.k_nig.2002.594">König et al 2002</a>, <a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>]. Bilateral optic atrophy has been reported in one individual [<a class="bibr" href="#nsdhl-dis.REF.knape.2010" rid="nsdhl-dis.REF.knape.2010">Knape et al 2010</a>], as have thrombocytosis and congenital bilateral dislocation of the hip [<a class="bibr" href="#nsdhl-dis.REF.chander.2010.6" rid="nsdhl-dis.REF.chander.2010.6">Chander et al 2010</a>]. Ipsilateral vocal cord paralysis and liver lobe and spleen hypertrophy have been reported [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>]. Small intestinal mucosal xanthoma have also been reported [<a class="bibr" href="#nsdhl-dis.REF.ryan.2013.1094" rid="nsdhl-dis.REF.ryan.2013.1094">Ryan et al 2013</a>, <a class="bibr" href="#nsdhl-dis.REF.tan.2022.e1848" rid="nsdhl-dis.REF.tan.2022.e1848">Tan et al 2022</a>]. Teeth are typically normal.</p><p><b>Prognosis.</b> It is unknown whether life span in females with CHILD syndrome is abnormal. Based on current data, life span is not limited by this condition, as several adults have been reported. CHILD syndrome was reported with phenotypes ranging from mild to severe in three different generations, with the oldest reported individual clinically and molecularly diagnosed at age 82 years [<a class="bibr" href="#nsdhl-dis.REF.bittar.2006.348" rid="nsdhl-dis.REF.bittar.2006.348">Bittar et al 2006</a>]. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.</p><p><b>Hemizygous males.</b> CHILD syndrome-associated <i>NSDHL</i> pathogenic variants are usually lethal to males during gestation. A few males with CHILD syndrome have been reported, and survival in these instances has been attributed to postzygotic somatic mutation in <i>NSDHL</i>. One reported male with the typical skin findings seen in females and normal development was mosaic for <i>NSDHL</i> pathogenic variant <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.262C>T</a> (p.Arg88Ter) [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>].</p></div><div id="nsdhl-dis.CK_Syndrome"><h4>CK Syndrome</h4><p>CK syndrome is characterized by intellectual disability, behavior issues, seizures, characteristic facial features, thin habitus, and ocular manifestations in males. To date, 25 affected males from three unrelated families have been reported [<a class="bibr" href="#nsdhl-dis.REF.garg.2021.201" rid="nsdhl-dis.REF.garg.2021.201">Garg et al 2021</a>].</p><p><b>Development.</b> Affected males have mild-to-severe intellectual disability. Most cannot speak.</p><p><b>Neurobehavioral/psychiatric manifestations.</b> Most males with CK syndrome manifest aggression, attention-deficit/hyperactivity disorder (ADHD), and irritability. These behaviors appear in infancy and early childhood. According to the Autism Diagnostic Review (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), affected males do not fulfill the criteria for an autism spectrum disorder.</p><p><b>Neurologic findings.</b> All affected males have developed seizures in infancy. These range from multiple daily episodes of brief unresponsiveness associated with staring and facial and/or limb twitching to prolonged generalized tonic-clonic seizures. These likely arise from cerebral cortical malformations that, by MRI examination, are most consistent with polymicrogyria. Spasticity, tetraparesis, development of contractures, and sensory neuropathy have also been reported [<a class="bibr" href="#nsdhl-dis.REF.garg.2021.201" rid="nsdhl-dis.REF.garg.2021.201">Garg et al 2021</a>].</p><p><b>Characteristic craniofacial features</b> (see <a class="figpopup" href="/books/NBK51754/figure/nsdhl-dis.F2/?report=objectonly" target="object" rid-figpopup="fignsdhldisF2" rid-ob="figobnsdhldisF2">Figure 2</a>). All affected males have microcephaly (greater than 2-3 standard deviations below the mean). Other features include plagiocephaly, a long, thin face, almond-shaped and upslanted palpebral fissures, epicanthal folds, posteriorly rotated ears, prominent nasal bridge, high palate, dental crowding, micrognathia, and malar hypoplasia.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="fignsdhldisF2" co-legend-rid="figlgndnsdhldisF2"><a href="/books/NBK51754/figure/nsdhl-dis.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="fignsdhldisF2" rid-ob="figobnsdhldisF2"><img class="small-thumb" src="/books/NBK51754/bin/nsdhl-dis-Image002.gif" src-large="/books/NBK51754/bin/nsdhl-dis-Image002.jpg" alt="Figure 2. . A male age 11 years (A, B) and a male age 22 years (C,D) with CK syndrome." /></a><div class="icnblk_cntnt" id="figlgndnsdhldisF2"><h4 id="nsdhl-dis.F2"><a href="/books/NBK51754/figure/nsdhl-dis.F2/?report=objectonly" target="object" rid-ob="figobnsdhldisF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">A male age 11 years (A, B) and a male age 22 years (C,D) with CK syndrome. Note the long thin face, epicanthal folds, almond-shaped palpebral fissures, prominent nasal bridge, and micrognathia. The long thin face becomes more apparent with age. </p></div></div><p><b>Skeletal manifestations and growth.</b> All males with CK syndrome have a thin habitus, and relatively long, thin limbs, fingers, and toes. Some individuals have scoliosis and kyphosis. Hyperextensibility can be seen as well. Linear growth is normal, and height of affected individuals is average for parental heights.</p><p><b>Ocular findings.</b> Strabismus is common. Optic atrophy is also seen.</p><p><b>Other.</b> Left ventricular concentric hypertrophy has been reported [<a class="bibr" href="#nsdhl-dis.REF.garg.2021.201" rid="nsdhl-dis.REF.garg.2021.201">Garg et al 2021</a>].</p><p><b>Prognosis.</b> It is unknown whether life span in males with CK syndrome is abnormal. One reported individual is alive at age 62 years [<a class="bibr" href="#nsdhl-dis.REF.du_souich.2009.2469" rid="nsdhl-dis.REF.du_souich.2009.2469">du Souich et al 2009</a>], demonstrating that survival into adulthood is possible. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.</p><p><b>Heterozygous females.</b> Females heterozygous for a CK syndrome-related <i>NSDHL</i> pathogenic variant have normal physical features, intellect, and brain imaging but may display behavioral problems including irritability and aggression [<a class="bibr" href="#nsdhl-dis.REF.herman.2012.301" rid="nsdhl-dis.REF.herman.2012.301">Herman & Kratz 2012</a>].</p></div></div><div id="nsdhl-dis.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p><b>CK syndrome.</b> The <i>NSDHL</i> pathogenic variants <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.455G>A</a>, <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.696_698delGAA</a>, and <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.1098dupT</a> have been consistently associated with CK syndrome.</p><p><b>CHILD syndrome.</b> Phenotypic variability within the spectrum of CHILD syndrome does not strictly correlate with the predicted severity of <i>NSDHL</i> pathogenic variants [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>, <a class="bibr" href="#nsdhl-dis.REF.mi.2015.e277" rid="nsdhl-dis.REF.mi.2015.e277">Mi et al 2015</a>].</p></div><div id="nsdhl-dis.Penetrance"><h3>Penetrance</h3><p>Penetrance appears to be complete in <i>NSDHL</i>-related disorders.</p></div><div id="nsdhl-dis.Nomenclature"><h3>Nomenclature</h3><p>CHILD syndrome is also known as unilateral congenital ichthyosiform erythroderma (CIE) and is a syndromic form of ichthyosis.</p></div><div id="nsdhl-dis.Prevalence"><h3>Prevalence</h3><p>The prevalence of CHILD syndrome is unknown; more than 60 individuals have been reported to date.</p><p>The prevalence of CK syndrome is unknown; it is thought to be rare. To date, 25 affected males from three unrelated families have been reported [<a class="bibr" href="#nsdhl-dis.REF.garg.2021.201" rid="nsdhl-dis.REF.garg.2021.201">Garg et al 2021</a>].</p></div></div><div id="nsdhl-dis.Genetically_Related_Allelic_Di"><h2 id="_nsdhl-dis_Genetically_Related_Allelic_Di_">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>NSDHL</i>.</p><p>A <b>contiguous gene duplication</b> in the Xq28 region involving <i>NSDHL</i> was reported in a male age eight years with limited social and verbal communication (including limited eye contact, significantly reduced facial expression, and poor verbal communication), restricted interests, attention deficits, and impulsive behavior meeting criteria for autism spectrum disorder. The child had mildly dysmorphic features including a depressed nasal bridge and thick, drooping upper eyelids. He exhibited hypotonia and poor motor coordination as an infant. The child had no major features of CK syndrome (specifically, he had no seizures) and no major features of CHILD syndrome [<a class="bibr" href="#nsdhl-dis.REF.hu.2018.192" rid="nsdhl-dis.REF.hu.2018.192">Hu et al 2018</a>]. The duplication was inherited from his mother, who displayed behavioral issues with normal physical features and intellect.</p></div><div id="nsdhl-dis.Differential_Diagnosis"><h2 id="_nsdhl-dis_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTgenesofinterestinthedif"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobnsdhldisTgenesofinterestinthedif"><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="nsdhl-dis.T.genes_of_interest_in_the_dif"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif/?report=objectonly" target="object" rid-ob="figobnsdhldisTgenesofinterestinthedif">Table 2. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of CHILD Syndrome </p></div></div><p>The X-linked inheritance, intellectual disability, and asthenic habitus of CK syndrome overlap with several disorders (see <a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif_1/?report=objectonly" target="object" rid-ob="figobnsdhldisTgenesofinterestinthedif1">Table 3</a>). (Note: For completeness, autosomal recessive and autosomal dominant disorders with phenotypes similar to CK syndrome are included in <a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif_1/?report=objectonly" target="object" rid-ob="figobnsdhldisTgenesofinterestinthedif1">Table 3</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTgenesofinterestinthedif1"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif_1/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobnsdhldisTgenesofinterestinthedif1"><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="nsdhl-dis.T.genes_of_interest_in_the_dif_1"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif_1/?report=objectonly" target="object" rid-ob="figobnsdhldisTgenesofinterestinthedif1">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of CK Syndrome </p></div></div></div><div id="nsdhl-dis.Management"><h2 id="_nsdhl-dis_Management_">Management</h2><p>No clinical practice guidelines for <i>NSDHL</i>-related disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with CHILD syndrome and CK syndrome.</p><div id="nsdhl-dis.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p><b>CHILD syndrome.</b> To establish the extent of disease and needs in an individual diagnosed with CHILD syndrome, the evaluations summarized in <a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_e/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndromerecommendede">Table 4a</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTchildsyndromerecommendede"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_e/?report=objectonly" target="object" title="Table 4a. " class="img_link icnblk_img" rid-ob="figobnsdhldisTchildsyndromerecommendede"><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="nsdhl-dis.T.child_syndrome_recommended_e"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_e/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndromerecommendede">Table 4a. </a></h4><p class="float-caption no_bottom_margin">CHILD Syndrome: Recommended Evaluations Following Initial Diagnosis </p></div></div><p><b>CK syndrome.</b> To establish the extent of disease and needs in an individual diagnosed with CK syndrome, the evaluations summarized in <a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_eval/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndromerecommendedeval">Table 4b</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTcksyndromerecommendedeval"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_eval/?report=objectonly" target="object" title="Table 4b. " class="img_link icnblk_img" rid-ob="figobnsdhldisTcksyndromerecommendedeval"><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="nsdhl-dis.T.ck_syndrome_recommended_eval"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_eval/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndromerecommendedeval">Table 4b. </a></h4><p class="float-caption no_bottom_margin">CK Syndrome: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="nsdhl-dis.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_treatment_of/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndrometreatmentof">Table 5a</a> and <a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_treatment_of_man/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndrometreatmentofman">5b</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTchildsyndrometreatmentof"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_treatment_of/?report=objectonly" target="object" title="Table 5a. " class="img_link icnblk_img" rid-ob="figobnsdhldisTchildsyndrometreatmentof"><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="nsdhl-dis.T.child_syndrome_treatment_of"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_treatment_of/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndrometreatmentof">Table 5a. </a></h4><p class="float-caption no_bottom_margin">CHILD Syndrome: Treatment of Manifestations </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTcksyndrometreatmentofman"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_treatment_of_man/?report=objectonly" target="object" title="Table 5b. " class="img_link icnblk_img" rid-ob="figobnsdhldisTcksyndrometreatmentofman"><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="nsdhl-dis.T.ck_syndrome_treatment_of_man"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_treatment_of_man/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndrometreatmentofman">Table 5b. </a></h4><p class="float-caption no_bottom_margin">CK Syndrome: Treatment of Manifestations </p></div></div><div id="nsdhl-dis.Developmental_Delay__Intellect"><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 between countries.</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, enrollment in developmental preschool through the local public school district is recommended. Before placement, an evaluation determines needed services and therapies and an individualized education plan (IEP) is developed for qualifying children based on motor, language, social, or cognitive delays. The early intervention program typically facilitates this transition. Developmental preschool is center based; home-based services are provided for medically unstable children unable to attend.</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 eligible children.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine the need for adjustments.</div></li><li class="half_rhythm"><div>Special education law mandates integrating children participating in an IEP into the least restrictive educational environment feasible, with inclusion in general education when suitable.</div></li><li class="half_rhythm"><div>Vision 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="nsdhl-dis.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 or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox<sup>®</sup>, anti-parkinsonian medications, 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="nsdhl-dis.NeurobehavioralPsychiatric_Con"><h4>Neurobehavioral/Psychiatric 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>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="nsdhl-dis.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_s/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndromerecommendeds">Tables 6a</a> and <a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_surv/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndromerecommendedsurv">6b</a> are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTchildsyndromerecommendeds"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_s/?report=objectonly" target="object" title="Table 6a. " class="img_link icnblk_img" rid-ob="figobnsdhldisTchildsyndromerecommendeds"><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="nsdhl-dis.T.child_syndrome_recommended_s"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_s/?report=objectonly" target="object" rid-ob="figobnsdhldisTchildsyndromerecommendeds">Table 6a. </a></h4><p class="float-caption no_bottom_margin">CHILD Syndrome: Recommended Surveillance </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTcksyndromerecommendedsurv"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_surv/?report=objectonly" target="object" title="Table 6b. " class="img_link icnblk_img" rid-ob="figobnsdhldisTcksyndromerecommendedsurv"><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="nsdhl-dis.T.ck_syndrome_recommended_surv"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_surv/?report=objectonly" target="object" rid-ob="figobnsdhldisTcksyndromerecommendedsurv">Table 6b. </a></h4><p class="float-caption no_bottom_margin">CK Syndrome: Recommended Surveillance </p></div></div></div><div id="nsdhl-dis.Evaluation_of_Relatives_at_Ris"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#nsdhl-dis.Related_Genetic_Counseling_Iss">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="nsdhl-dis.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><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. Note: There may not be clinical trials for this disorder.</p></div></div><div id="nsdhl-dis.Genetic_Counseling"><h2 id="_nsdhl-dis_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="nsdhl-dis.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>NSDHL</i>-related disorders are inherited in an X-linked manner.</p><ul><li class="half_rhythm"><div>CHILD syndrome (associated with <i>NSDHL</i> pathogenic variants that result in loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase, the protein encoded by <i>NSDHL</i>) is usually male lethal during gestation and thus predominantly affects females.</div></li><li class="half_rhythm"><div>CK syndrome (associated with hypomorphic <i>NSDHL</i> pathogenic variants that result in partial loss of functional decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase) predominantly affects males.</div></li></ul></div><div id="nsdhl-dis.CHILD_Syndrome__Risk_to_Family"><h3>CHILD Syndrome – Risk to Family Members</h3><p>
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<b>Parents of a female proband</b>
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</p><ul><li class="half_rhythm"><div>A female proband may have inherited the <i>NSDHL</i> pathogenic variant from her mother or the pathogenic variant may be <i>de novo</i>. Theoretically, an affected female may have inherited the pathogenic variant from a father with gonadal mosaicism.</div></li><li class="half_rhythm"><div>Molecular genetic testing of the mother is recommended to confirm her genetic status and to allow reliable recurrence risk assessment. Although CHILD syndrome-associated <i>NSDHL</i> pathogenic variants appear to be highly penetrant, mothers heterozygous for an <i>NSDHL</i> pathogenic variant who have only mild skin lesions, Blaschko-linear inflammatory scaly lesions, patchy alopecia, and nail changes have been reported [<a class="bibr" href="#nsdhl-dis.REF.bittar.2006.348" rid="nsdhl-dis.REF.bittar.2006.348">Bittar et al 2006</a>]. Favorably skewed X-chromosome inactivation has been proposed to explain this milder phenotype, and theoretically could on occasion result in a phenotypically normal heterozygous female. Therefore, <i>de novo</i> occurrence of an <i>NSDHL</i> pathogenic variant in the proband cannot be confirmed unless molecular genetic testing has demonstrated that the mother is not heterozygous for the <i>NSDHL</i> pathogenic variant.</div></li></ul><p>
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<b>Parents of a male proband</b>
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</p><ul><li class="half_rhythm"><div>If a male proband has CHILD syndrome as the result of mosaicism for a postzygotic <i>NSDHL</i> pathogenic variant [<a class="bibr" href="#nsdhl-dis.REF.bornholdt.2005.e17" rid="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt et al 2005</a>], neither the mother nor the father is heterozygous or hemizygous, respectively, for the pathogenic variant.</div></li><li class="half_rhythm"><div>An affected male fetus may have inherited the <i>NSDHL</i> pathogenic variant from his mother or the pathogenic variant may be <i>de novo</i>. Transmission of an <i>NSDHL</i> pathogenic variant from an unaffected mother to affected male fetuses has been reported [<a class="bibr" href="#nsdhl-dis.REF.zhuang.2023.e2121" rid="nsdhl-dis.REF.zhuang.2023.e2121">Zhuang et al 2023</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing of the mother is recommended to confirm her genetic status and allow reliable recurrence risk assessment.</div></li></ul><p><b>Sibs of a female proband.</b> The risk to sibs depends on the genetic status of the mother.</p><ul><li class="half_rhythm"><div>If the mother of the proband has an <i>NSDHL</i> pathogenic variant, the chance of transmitting it in each pregnancy is 50%. However, since studies suggest that male conceptuses with an <i>NSDHL</i> pathogenic variant generally abort or resorb spontaneously [<a class="bibr" href="#nsdhl-dis.REF.cunningham.2005.1150" rid="nsdhl-dis.REF.cunningham.2005.1150">Cunningham et al 2005</a>], the expected live-born distribution is:</div><ul><li class="half_rhythm"><div>33% heterozygous (typically) affected females;</div></li><li class="half_rhythm"><div>33% unaffected females who have not inherited the <i>NSDHL</i> pathogenic variant;</div></li><li class="half_rhythm"><div>33% unaffected males who have not inherited the <i>NSDHL</i> pathogenic variant.</div></li></ul></li><li class="half_rhythm"><div>If the proband represents a simplex case (i.e., a single affected family member) and if pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of the mother, the risk to sibs is slightly greater than that of the general population (though still <1%) because of the possibility of maternal gonadal mosaicism.</div></li><li class="half_rhythm"><div>Theoretically, if the father of a female proband has gonadal mosaicism for an <i>NSDHL</i> pathogenic variant, all female sibs are at risk of inheriting the pathogenic variant and being affected; male sibs are not at risk of inheriting the pathogenic variant.</div></li></ul><p>
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<b>Offspring of a female proband</b>
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</p><ul><li class="half_rhythm"><div>The risk to the offspring of a female with CHILD syndrome must take into consideration the presumed lethality to affected males during gestation. At conception, the chance of transmitting the pathogenic variant in each pregnancy is 50%; however, since male conceptuses with an <i>NSDHL</i> pathogenic variant generally abort or resorb spontaneously, the expected live-born distribution is 33% (typically) affected females, 33% unaffected females, and 33% unaffected males.</div></li><li class="half_rhythm"><div>Of note, a female proband with comparatively minor skin lesions (e.g., an ichthyosiform nevus without any additional manifestations of CHILD syndrome) is at risk of having a daughter with typical CHILD syndrome [<a class="bibr" href="#nsdhl-dis.REF.happle.1995.210" rid="nsdhl-dis.REF.happle.1995.210">Happle et al 1995</a>].</div></li></ul><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's mother: if the proband's mother has the <i>NSDHL</i> pathogenic variant, her family members may be at risk.</p></div><div id="nsdhl-dis.Risk_to_Family_Members__CK_Syn"><h3>Risk to Family Members ‒ CK Syndrome</h3><p>
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<b>Parents of a male proband</b>
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</p><ul><li class="half_rhythm"><div>The father of a male with CK syndrome will not have the disorder nor will he be hemizygous for the <i>NSDHL</i> pathogenic variant; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. Note: If a female has more than one affected child and no other affected relatives and if the <i>NSDHL</i> pathogenic variant cannot be detected in her leukocyte DNA, she most likely has gonadal mosaicism.</div></li><li class="half_rhythm"><div>If a male is the only affected family member, the mother may be a heterozygote, the affected male may have a <i>de novo</i>
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<i>NSDHL</i> pathogenic variant (in which case the mother is not a heterozygote), or the mother may have somatic/gonadal mosaicism. The frequency of <i>de novo</i> pathogenic variants is unknown.</div></li><li class="half_rhythm"><div>Molecular genetic testing of the mother is recommended to confirm her genetic status and allow reliable recurrence risk assessment.</div></li></ul><p><b>Sibs of a male proband.</b> The risk to sibs depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the proband is heterozygous for an <i>NSDHL</i> pathogenic variant, the expected chance of transmitting it in each pregnancy is 50%.</div><ul><li class="half_rhythm"><div>Males who inherit the pathogenic variant will be affected;</div></li><li class="half_rhythm"><div>Females who inherit the pathogenic variant will be heterozygous and may have a range of behavioral problems (see Clinical Description, <a href="#nsdhl-dis.CK_Syndrome">CK Syndrome</a>, <b>Heterozygous females</b>).</div></li></ul></li><li class="half_rhythm"><div>If the proband represents a simplex case and if the <i>NSDHL</i> pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population because of the possibility of maternal gonadal mosaicism.</div></li></ul><p><b>Offspring of a male proband.</b> To date, no male with CK syndrome has reproduced.</p><p><b>Other family members.</b> The maternal aunts and maternal cousins of a male proband may be at risk of having an <i>NSDHL</i> pathogenic variant.</p><p><b>Heterozygote detection.</b> Identification of female heterozygotes requires prior identification of the <i>NSDHL</i> pathogenic variant in the family.</p><p>Note: Heterozygous females may have a range of behavioral problems (see Clinical Description, <a href="#nsdhl-dis.CK_Syndrome">CK Syndrome</a>, <b>Heterozygous females</b>).</p></div><div id="nsdhl-dis.Related_Genetic_Counseling_Iss"><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 young adults who are affected, heterozygous, or at risk of being heterozygous.</div></li></ul></div><div id="nsdhl-dis.Prenatal_Testing_and_Preimplan"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>NSDHL</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for an <i>NSDHL</i>-related disorder are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="nsdhl-dis.Resources"><h2 id="_nsdhl-dis_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>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Congenital hemidysplasia with ichthyosiform erythroderma and limb defects</a>
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</div></li><li class="half_rhythm"><div>
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<b>Foundation for Ichthyosis and Related Skin Types, Inc. (FIRST)</b>
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</div><div><b>Phone:</b> 215-997-9400; 800-545-3286</div><div><b>Email:</b> info@firstskinfoundation.org</div><div>
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<a href="http://www.firstskinfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">firstskinfoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Rare Disease Foundation</b>
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</div><div>Canada</div><div><b>Email:</b> families@rarediseasefoundation.org; info@rarediseasefoundation.org</div><div>
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<a href="https://rarediseasefoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rarediseasefoundation.org</a>
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</div></li></ul>
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</div><div id="nsdhl-dis.Molecular_Genetics"><h2 id="_nsdhl-dis_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="fignsdhldismolgenTA"><a href="/books/NBK51754/table/nsdhl-dis.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobnsdhldismolgenTA"><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="nsdhl-dis.molgen.TA"><a href="/books/NBK51754/table/nsdhl-dis.molgen.TA/?report=objectonly" target="object" rid-ob="figobnsdhldismolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">NSDHL-Related Disorders: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldismolgenTB"><a href="/books/NBK51754/table/nsdhl-dis.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobnsdhldismolgenTB"><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="nsdhl-dis.molgen.TB"><a href="/books/NBK51754/table/nsdhl-dis.molgen.TB/?report=objectonly" target="object" rid-ob="figobnsdhldismolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for NSDHL-Related Disorders (View All in OMIM) </p></div></div><div id="nsdhl-dis.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>NSDHL</i> encodes decarboxylating sterol-4-alpha-carboxylate 3-dehydrogenase. This enzyme localizes to the surface of the endoplasmic reticulum and to lipid droplets. It is a member of a multiprotein complex and functions as a C4 demethylase in post-squalene cholesterol biosynthesis [<a class="bibr" href="#nsdhl-dis.REF.gachotte.1998.13794" rid="nsdhl-dis.REF.gachotte.1998.13794">Gachotte et al 1998</a>, <a class="bibr" href="#nsdhl-dis.REF.mo.2002.9739" rid="nsdhl-dis.REF.mo.2002.9739">Mo et al 2002</a>, <a class="bibr" href="#nsdhl-dis.REF.caldas.2003.2981" rid="nsdhl-dis.REF.caldas.2003.2981">Caldas & Herman 2003</a>].</p><p><b>Mechanism of disease causation.</b> Well-studied CHILD syndrome-associated <i>NSDHL</i> variants result in loss of function of the protein, and many are null alleles. CK syndrome-associated variants cause partial loss of enzyme function.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fignsdhldisTnsdhlpathogenicvariantsre"><a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre"><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="nsdhl-dis.T.nsdhl_pathogenic_variants_re"><a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">Table 7. </a></h4><p class="float-caption no_bottom_margin"><i>NSDHL</i> Pathogenic Variants Referenced in This <i>GeneReview</i> </p></div></div></div></div><div id="nsdhl-dis.Chapter_Notes"><h2 id="_nsdhl-dis_Chapter_Notes_">Chapter Notes</h2><div id="nsdhl-dis.Author_History"><h3>Author History</h3><p>Cornelius F Boerkoel, MD, PhD; University of British Columbia (2010-2024)<br />Christèle du Souich, MSc, CCGC, CGC; University of British Columbia (2010-2024)<br />Jinia El Feghaly, MD (2024-present)<br />Karl-Heinz Grzeschik, PhD; Philipps-Universität, Marburg (2010-2024)<br />Lamiaa Hamie, MD, MSc (2024-present)<br />Arne König, MD; Philipps-Universität, Marburg (2010-2015)<br />Mazen Kurban, MD (2024-present)<br />F Lucy Raymond, MD, PhD; University of Cambridge (2010-2024)</p></div><div id="nsdhl-dis.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>5 September 2024 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 October 2018 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 November 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 June 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>1 February 2011 (me) Review posted live</div></li><li class="half_rhythm"><div>9 January 2010 (cb) Original submission</div></li></ul></div></div><div id="nsdhl-dis.References"><h2 id="_nsdhl-dis_References_">References</h2><div id="nsdhl-dis.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.alexopoulos.2015.e145">Alexopoulos
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A, Kakourou
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T.
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CHILD syndrome: successful treatment of skin lesions with topical simvastatin/cholesterol ointment--a case report.
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Pediatr Dermatol.
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2015;32:e145–7.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/25845514" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25845514</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.avgerinou.2010.733">Avgerinou
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GP, Asvesti
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AP, Katsambas
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AD, Nikolaou
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VA, Christofidou
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EC, Grzeschik
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KH, Happle
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R. CHILD syndrome: the NSDHL gene and its role in CHILD syndrome, a rare hereditary disorder.
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J Eur Acad Dermatol Venereol.
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2010;24:733–6.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/19906044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19906044</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.bajawi.2018.232">Bajawi
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SM, Jafarri
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SA, Buraik
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MA, Al Attas
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KM, Hannani
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HY. Pathogenesis-based therapy: cutaneous abnormalities of CHILD syndrome successfully treated with topical simvastatin monotherapy.
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JAAD Case Rep.
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2018;4:232–4.
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[<a href="/pmc/articles/PMC5909487/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5909487</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29687057" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29687057</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.bergqvist.2018.733">Bergqvist
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C, Abdallah
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B, Hasbani
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DJ, Abbas
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O, Kibbi
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AG, Kurban
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M, Rubeiz
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N. CHILD syndrome: a modified pathogenesis-targeted therapeutic approach.
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Am J Med Genet A.
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2018;176:733–8.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/29392821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29392821</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.bittar.2006.348">Bittar
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M, Happle
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R, Grzeschik
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KH, Leveleki
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L, Hertl
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M, Bornholdt
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D, König
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A. CHILD syndrome in 3 generations: the importance of mild or minimal skin lesions.
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Arch Dermatol.
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2006;142:348–51.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/16549711" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16549711</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.bornholdt.2005.e17">Bornholdt
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D, König
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A, Happle
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R, Leveleki
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L, Bittar
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M, Danarti
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R, Vahlquist
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A, Tilgen
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W, Reinhold
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U, Poiares Baptista
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A, Grosshans
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E, Vabres
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P, Niiyama
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S, Sasaoka
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K, Tanaka
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T, Meiss
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AL, Treadwell
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PA, Lambert
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D, Camacho
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F, Grzeschik
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KH. Mutational spectrum of NSDHL in CHILD syndrome.
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J Med Genet.
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2005;42:e17.
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CHILD syndrome mimicking verrucous nevus in a Chinese patient responded well to topical therapy of compound of simvastatin and cholesterol.
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JEADV. 2018;32:1209–13.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/29341259" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29341259</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="nsdhl-dis.REF.zhuang.2023.e2121">Zhuang
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[<a href="/pmc/articles/PMC10009909/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10009909</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36504312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36504312</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK51754_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Mazen Kurban</span>, MD<div class="affiliation small">Tenured Professor of Dermatology<br />Biochemistry and Molecular Genetics<br />American University of Beirut Medical Center<br />Beirut, Lebanon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="bl.ude.bua@401km" class="oemail">bl.ude.bua@401km</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jinia El Feghaly</span>, MD<div class="affiliation small">Assistant Professor of Dermatology and Pediatrics<br />University of Rochester Medical Center<br />Rochester, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@dmylahgefleainij" class="oemail">moc.liamg@dmylahgefleainij</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Lamiaa Hamie</span>, MD, MSc<div class="affiliation small">Specialist Dermatologist<br />Mediclinic Middle East<br />Dubai, United Arab Emirates<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.kooltuo@eimahaaimal.rd" class="oemail">moc.kooltuo@eimahaaimal.rd</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">February 1, 2011</span>; Last Update: <span itemprop="dateModified">September 5, 2024</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Kurban M, El Feghaly J, Hamie L. NSDHL-Related Disorders. 2011 Feb 1 [Updated 2024 Sep 5]. 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/nr2f1-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/nthl1-ts/?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="figobnsdhldisTc"><div id="nsdhl-dis.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NSDHL</i>-Related Disorders: Included Phenotypes</th></tr></thead><tbody><tr><td headers="hd_h_nsdhl-dis.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>CHILD (<i>c</i>ongenital <i>h</i>emidysplasia with <i>i</i>chthyosiform nevus and <i>l</i>imb <i>d</i>efects) syndrome</div></li><li class="half_rhythm"><div>CK syndrome</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">For synonyms and outdated names see <a href="#nsdhl-dis.Nomenclature">Nomenclature</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTmoleculargenetictestingus"><div id="nsdhl-dis.T.molecular_genetic_testing_us" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>NSDHL</i>-Related Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.molecular_genetic_testing_us/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.molecular_genetic_testing_us_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_2" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr><tr><th headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3" id="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">CHILD syndrome</th><th headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3" id="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CK syndrome</th></tr></thead><tbody><tr><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>NSDHL</i>
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</td><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3 hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~90% <sup>4</sup></td><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3 hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>4, 5</sup></td></tr><tr><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_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_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3 hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~10% <sup>4, 7</sup></td><td headers="hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_1_3 hd_h_nsdhl-dis.T.molecular_genetic_testing_us_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>4, 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="nsdhl-dis.TF.1.1"><p class="no_margin">See <a href="/books/NBK51754/?report=reader#nsdhl-dis.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="nsdhl-dis.TF.1.2"><p class="no_margin">See <a href="#nsdhl-dis.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="nsdhl-dis.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="nsdhl-dis.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#nsdhl-dis.REF.stenson.2020.1197" rid="nsdhl-dis.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="nsdhl-dis.TF.1.5"><p class="no_margin">To date, only one of three <i>NSDHL</i> pathogenic variants have been identified in individuals reported with CK syndrome (<a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.455G>A</a>, <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.696_698delGAA</a>, and <a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object" rid-ob="figobnsdhldisTnsdhlpathogenicvariantsre">c.1098dupT</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="nsdhl-dis.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. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="nsdhl-dis.TF.1.7"><p class="no_margin">Large intragenic deletion/duplications have not been reported in individuals with CK syndrome. One individual with a contiguous gene duplication (not included in these calculations) has been reported (see <a href="#nsdhl-dis.Genetically_Related_Allelic_Di">Genetically Related Disorders</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTgenesofinterestinthedif"><div id="nsdhl-dis.T.genes_of_interest_in_the_dif" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of CHILD Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.genes_of_interest_in_the_dif_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Key Features of Disorder</th></tr><tr><th headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4" id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/CHILD syndrome</th><th headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4" id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from CHILD syndrome</th></tr></thead><tbody><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EBP</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/x-dcdp/?report=reader">Chondrodysplasia punctata 2, X-linked</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>≥95% of affected persons are female.</div></li><li class="half_rhythm"><div>Linear or blotchy scaly ichthyosiform plaques in newborns; later appearance of linear or whorled atrophic patches involving hair follicles (follicular atrophoderma) & scarring</div></li><li class="half_rhythm"><div>Asymmetric limb shortening, kyphoscoliosis, & chondrodysplasia punctata (epiphyseal stippling)</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of strict midline demarcation & lack of unilaterality seen in CHILD syndrome</div></li><li class="half_rhythm"><div>Skin findings fade over time.</div></li><li class="half_rhythm"><div>Most persons have follicular atrophoderma by age 2 yrs.</div></li><li class="half_rhythm"><div>Ocular anomalies are prominent (develop early in life).</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HRAS</i>
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<br />
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<i>KRAS</i>
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<br />
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<i>NRAS</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Schimmelpenning-Feuerstein-Mims syndrome (OMIM <a href="https://omim.org/entry/163200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">163200</a>) & other epidermal nevus syndromes (ENSs)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skin lesions (epidermal nevi) can be flat, verrucous, inflammatory or non-inflammatory, scaly or non-scaly; they typically follow lines of Blaschko & many grow over time.</div></li><li class="half_rhythm"><div>In Schimmelpenning-Feuerstein-Mims syndrome face &/or scalp are typically involved.</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Extensive epidermal nevi (various subtypes); unilateral or bilateral</div></li><li class="half_rhythm"><div>Cerebral anomalies & neurologic symptoms</div></li><li class="half_rhythm"><div>Coloboma of iris, choroid, or eyelids</div></li><li class="half_rhythm"><div>Conjunctival lipodermoid</div></li><li class="half_rhythm"><div>Overgrowth & other vascular lesions seen in some ENSs</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>IKBKG</i> (formerly <i>NEMO</i>)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/i-p/?report=reader">Incontinentia pigmenti</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Embryonic lethality in many males</div></li><li class="half_rhythm"><div>Skin lesions present as erythema & then blisters at birth (vesicular stage), progress to wart-like rash (verrucous stage), swirling macular hyperpigmentation following lines of Blaschko (hyperpigmented stage), & then linear hypopigmentation (hypopigmented stage). <sup>2</sup></div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cutaneous lesions evolve through multiple stages.</div></li><li class="half_rhythm"><div>Hypodontia</div></li><li class="half_rhythm"><div>Onychogryphosis</div></li><li class="half_rhythm"><div>Ocular findings (mostly retinal; peripheral neovascularization in eyes)</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>ID</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">ID = intellectual disability; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="nsdhl-dis.TF.2.1"><p class="no_margin">Not known to be inherited. Postzygotic somatic mosaic pathogenic variants in <i>HRAS</i>, <i>KRAS</i>, or <i>NRAS</i> have been reported in lesional tissue of some individuals with Schimmelpenning-Feuerstein-Mims syndrome. Most epidermal nevus syndromes are associated with postzygotic somatic pathogenic variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="nsdhl-dis.TF.2.2"><p class="no_margin">The evolution of the four skin stages in incontinentia pigmenti may or may not occur in all individuals.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTgenesofinterestinthedif1"><div id="nsdhl-dis.T.genes_of_interest_in_the_dif_1" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of CK Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.genes_of_interest_in_the_dif_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.genes_of_interest_in_the_dif_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Key Features of Disorder</th></tr><tr><th headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4" id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/CK syndrome</th><th headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4" id="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from CK syndrome</th></tr></thead><tbody><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATP6AP2</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X-linked intellectual developmental disorder w/epilepsy (OMIM <a href="https://omim.org/entry/300423" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300423</a>)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Generalized tonic-clonic seizures</div></li><li class="half_rhythm"><div>Scoliosis</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progressive gait disturbance</div></li><li class="half_rhythm"><div>Pes planus</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATRX</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/xlmr/?report=reader">Alpha-thalassemia X-linked intellectual disability syndrome</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID; severe speech delay</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Narrow face; slanted palpebral fissures</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Infantile hypotonia; development of hypertonia in adolescence to early adulthood</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MED12</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lujan syndrome (also referred to as Lujan-Fryns syndrome; see <a href="/books/n/gene/fg/?report=reader"><i>MED12</i>-Related Disorders</a>)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Marfanoid appearance; thin fingers & toes</div></li><li class="half_rhythm"><div>Tall, narrow face; prominent nasal bridge; high, narrow palate; micrognathia; low-set, posteriorly rotated ears</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Large head circumference</div></li><li class="half_rhythm"><div>Short philtrum</div></li><li class="half_rhythm"><div>Hypernasal speech</div></li><li class="half_rhythm"><div>Generalized hypotonia; abnormalities of corpus callosum</div></li><li class="half_rhythm"><div>Pectus excavatum</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MMACHC</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Methylmalonic aciduria & homocystinuria, cblC type (early-onset form) (See <a href="/books/n/gene/cbl/?report=reader">Disorders of Intracellular Cobalamin Metabolism</a>.)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Microcephaly</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Congenital heart malformation</div></li><li class="half_rhythm"><div>Pigmentary retinopathy</div></li><li class="half_rhythm"><div>Megaloblastic anemia</div></li><li class="half_rhythm"><div>Poor weight gain, feeding difficulties, vomiting, lethargy <sup>1</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PQBP1</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renpenning syndrome (OMIM <a href="https://omim.org/entry/309500" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">309500</a>)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Microcephaly</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Heart defects</div></li><li class="half_rhythm"><div>Cleft palate</div></li><li class="half_rhythm"><div>Microphthalmia</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SKI</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sgs/?report=reader">Shprintzen-Goldberg syndrome</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Marfanoid habitus</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Craniosynostosis</div></li><li class="half_rhythm"><div>Cardiovascular & abdominal wall defects</div></li><li class="half_rhythm"><div>Minimal subcutaneous fat</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC9A6</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/christianson/?report=reader">Christianson syndrome</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Epilepsy</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Truncal ataxia</div></li><li class="half_rhythm"><div>Absent or limited speech</div></li><li class="half_rhythm"><div>Ophthalmoplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SMS</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/snyder-robinson/?report=reader">Snyder-Robinson syndrome</a>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Asthenic build</div></li><li class="half_rhythm"><div>High-arched palate</div></li><li class="half_rhythm"><div>Kyphoscoliosis</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prominent lower lip</div></li><li class="half_rhythm"><div>Osteoporosis</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Unsteady gait</div></li><li class="half_rhythm"><div>Hypernasal speech in some affected males (may also be dysarthric, coarse, or absent)</div></li></ul>
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</td></tr><tr><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ZDHHC9</i>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ZDHHC9-</i>related intellectual developmental disorder (OMIM <a href="https://omim.org/entry/300799" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300799</a>)</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Thin habitus; long face & digits</div></li><li class="half_rhythm"><div>ID</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_1_4 hd_h_nsdhl-dis.T.genes_of_interest_in_the_dif_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Joint hypermobility</div></li><li class="half_rhythm"><div>Absence of other dysmorphic features</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="nsdhl-dis.TF.3.1"><p class="no_margin">
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<a class="bibr" href="#nsdhl-dis.REF.head.2023.436" rid="nsdhl-dis.REF.head.2023.436">Head et al [2023]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTchildsyndromerecommendede"><div id="nsdhl-dis.T.child_syndrome_recommended_e" class="table"><h3><span class="label">Table 4a. </span></h3><div class="caption"><p>CHILD Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_e/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.child_syndrome_recommended_e_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_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_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Integument</b>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dermatologic eval</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_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_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Radiographs as needed of extremities & spine</div></li><li class="half_rhythm"><div>Clinical assessment for joint contractures & scoliosis</div></li><li class="half_rhythm"><div>Referral to orthopedist as needed</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for skeletal malformations incl scoliosis.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" rowspan="2" scope="row" 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_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to neurologist</div></li><li class="half_rhythm"><div>EEG</div></li><li class="half_rhythm"><div>Brain MRI/CT</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_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_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac</b>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for congenital heart disease.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Pulmonary</b>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chest imaging</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for lung hypoplasia.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="row" rowspan="1" 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_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal & pelvic ultrasound</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for renal or other genitourinary anomalies.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_e_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of CHILD syndrome to facilitate medical & personal decision making</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">MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="nsdhl-dis.TF.4a.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTcksyndromerecommendedeval"><div id="nsdhl-dis.T.ck_syndrome_recommended_eval" class="table"><h3><span class="label">Table 4b. </span></h3><div class="caption"><p>CK Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_eval/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.ck_syndrome_recommended_eval_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_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_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_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_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurobehavioral/</b>
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<br />
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<b>Psychiatric</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For persons age >12 mos if behavioral issues are present: screening for concerns incl aggression, ADHD, & irritability</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to psychiatrist as needed</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_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_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to neurologist</div></li><li class="half_rhythm"><div>EEG</div></li><li class="half_rhythm"><div>Brain MRI/CT</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for seizures.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_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_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Spine radiographs as needed</div></li><li class="half_rhythm"><div>Referral to orthopedist as needed</div></li></ul>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for scoliosis/kyphosis.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology exam</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for ocular findings incl strabismus & optic atrophy.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_eval_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of CK syndrome to facilitate medical & personal decision making</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">ADHD = attention-deficit/hyperactivity disorder; MOI = mode of inheritance</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTchildsyndrometreatmentof"><div id="nsdhl-dis.T.child_syndrome_treatment_of" class="table"><h3><span class="label">Table 5a. </span></h3><div class="caption"><p>CHILD Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_treatment_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.child_syndrome_treatment_of_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_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_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Inflammatory nevi</b>
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</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Oral & topical</b> ketoconazole resulted in a 90% reduction of lesions after 10 days of therapy. <sup>1</sup></td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;"><b>Note:</b> (1) To date, no therapy appears to ameliorate the cutaneous findings for every person w/CHILD syndrome. Trying different methods until the clinician finds a successful therapy appears to be typical for most affected persons. Recent therapies aim to address cholesterol deficiency & ↓ accumulation of toxic precursors. (2) Topical cholesterol application alone was reported to have no satisfactory effect. <sup>12</sup></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>Topical treatments:</b>
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|
<ul><li class="half_rhythm"><div>Lovastatin 2% / cholesterol 2% led to complete healing in a few persons. <sup>2</sup></div></li><li class="half_rhythm"><div>Simvastatin 2% ointment led to remarkable improvement in 1 person. <sup>3</sup></div></li><li class="half_rhythm"><div>Simvastatin 5% in a petroleum base led to clearance after 4 wks. <sup>4</sup></div></li><li class="half_rhythm"><div>Combined simvastatin 2% & cholesterol corrected the cutaneous phenotype of 1 person. <sup>5</sup></div></li><li class="half_rhythm"><div>Simvastatin was ↑ from 2.5% to 5% to enhance effectiveness of treatment. <sup>6</sup></div></li><li class="half_rhythm"><div>The addition of glycolic acid to cholesterol & lovastatin creams improved penetrance of therapy into thick skin scales, thus improving treatment. <sup>7</sup></div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>Dermatologic surgery:</b>
|
|
<ul><li class="half_rhythm"><div>Grafting skin obtained from contralateral unaffected region was successful in 1 person. <sup>8</sup></div></li><li class="half_rhythm"><div>Removal by dermabrasion was reported; however, it recurred w/in 8 mos. <sup>9</sup></div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>Oral aromatic retinoids</b> (etretinate) may ameliorate cutaneous symptoms; however, this drug is often poorly tolerated <sup>10</sup> & does not prove effective in every person. <sup>11</sup></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Itching / Dry skin</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lactic acid 12% creams or lotions for itching</div></li><li class="half_rhythm"><div>Urea creams for dry skin</div></li></ul>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Orthopedic abnormalities</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of orthopedic abnormalities such as scoliosis & joint contractures w/braces &/or corrective surgery</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Heart defects</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt per cardiologist</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Lung hypoplasia</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt per pulmonologist</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Renal manifestations</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt per nephrologist</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_treatment_of_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="nsdhl-dis.TF.5a.1"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.liu.2015.91" rid="nsdhl-dis.REF.liu.2015.91">Liu et al [2015]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="nsdhl-dis.TF.5a.2"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.joosten.2022" rid="nsdhl-dis.REF.joosten.2022">Joosten et al [2022]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="nsdhl-dis.TF.5a.3"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.bajawi.2018.232" rid="nsdhl-dis.REF.bajawi.2018.232">Bajawi et al [2018]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="nsdhl-dis.TF.5a.4"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.kallis.2022.151" rid="nsdhl-dis.REF.kallis.2022.151">Kallis et al [2022]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="nsdhl-dis.TF.5a.5"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.alexopoulos.2015.e145" rid="nsdhl-dis.REF.alexopoulos.2015.e145">Alexopoulos & Kakourou [2015]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="nsdhl-dis.TF.5a.6"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.yu.2020.e8" rid="nsdhl-dis.REF.yu.2020.e8">Yu et al [2020]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="nsdhl-dis.TF.5a.7"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.bergqvist.2018.733" rid="nsdhl-dis.REF.bergqvist.2018.733">Bergqvist et al [2018]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="nsdhl-dis.TF.5a.8"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.k_nig.2010.340" rid="nsdhl-dis.REF.k_nig.2010.340">König et al [2010]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="nsdhl-dis.TF.5a.9"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.happle.1996.192" rid="nsdhl-dis.REF.happle.1996.192">Happle et al [1996]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="nsdhl-dis.TF.5a.10"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.happle.1980.27" rid="nsdhl-dis.REF.happle.1980.27">Happle et al [1980]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="nsdhl-dis.TF.5a.11"><p class="no_margin">
|
|
<a class="bibr" href="#nsdhl-dis.REF.liu.2015.91" rid="nsdhl-dis.REF.liu.2015.91">Liu et al [2015]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>12. </dt><dd><div id="nsdhl-dis.TF.5a.12"><p class="no_margin"><a class="bibr" href="#nsdhl-dis.REF.merino_de_paz.2011.1026" rid="nsdhl-dis.REF.merino_de_paz.2011.1026">Merino De Paz et al [2011]</a>, <a class="bibr" href="#nsdhl-dis.REF.paller.2011.2242" rid="nsdhl-dis.REF.paller.2011.2242">Paller et al [2011]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTcksyndrometreatmentofman"><div id="nsdhl-dis.T.ck_syndrome_treatment_of_man" class="table"><h3><span class="label">Table 5b. </span></h3><div class="caption"><p>CK Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_treatment_of_man/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.ck_syndrome_treatment_of_man_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_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_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Developmental delay / Intellectual disability / Neurobehavioral issues</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#nsdhl-dis.Developmental_Delay__Intellect">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavior modification &/or drug therapy to control aggression & help w/manifestations of ADHD.</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Epilepsy</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_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_nsdhl-dis.T.ck_syndrome_treatment_of_man_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; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Spasticity/</b>
|
|
<br />
|
|
<b>Tetraparesis/</b>
|
|
<br />
|
|
<b>Contractures</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT incl stretching to help avoid contractures & falls</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_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_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Scoliosis</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of scoliosis per orthopedist</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Eyes</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per ophthalmologist for strabismus</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Refractive errors</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Low vision services</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Children: through early intervention programs &/or school district</div></li><li class="half_rhythm"><div>Adults: low vision clinic &/or community vision services / OT / mobility services</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Family/Community</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_treatment_of_man_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_nsdhl-dis.T.ck_syndrome_treatment_of_man_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 <a href="https://www.specialolympics.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Special Olympics</a>.</div></li></ul>
|
|
</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">ADHD = attention-deficit/hyperactivity disorder; ASM = anti-seizure medication; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="nsdhl-dis.TF.5b.1"><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></div></div></div></article><article data-type="table-wrap" id="figobnsdhldisTchildsyndromerecommendeds"><div id="nsdhl-dis.T.child_syndrome_recommended_s" class="table"><h3><span class="label">Table 6a. </span></h3><div class="caption"><p>CHILD Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.child_syndrome_recommended_s/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.child_syndrome_recommended_s_lrgtbl__"><table><thead><tr><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_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_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Integument</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Examine for new cutaneous manifestations; new lesions may occur in puberty or early adulthood.</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_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_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for joint contractures & scoliosis</td></tr><tr><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic, cardiac, or kidney manifestations</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.child_syndrome_recommended_s_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment w/imaging as needed</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobnsdhldisTcksyndromerecommendedsurv"><div id="nsdhl-dis.T.ck_syndrome_recommended_surv" class="table"><h3><span class="label">Table 6b. </span></h3><div class="caption"><p>CK Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.ck_syndrome_recommended_surv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.ck_syndrome_recommended_surv_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_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_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Developmental</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as needed</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurobehavioral/</b>
|
|
<br />
|
|
<b>Psychiatric</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for aggression, ADHD, & irritability</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Seizures</b>
|
|
</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for new seizures or changes in seizures for readjustment of medications if necessary</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_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_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for scoliosis/kyphosis w/imaging as needed</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Ophthalmologic</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Follow-up ophthalmology exam</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As recommended by ophthalmologist</td></tr><tr><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Transition to adult care</b>
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</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Develop realistic plans for adult life (see <a href="https://www.aesnet.org/docs/default-source/pdfs-clinical/aestransitionspracticetool-devdelayedfinalapproved4-21-132.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">American Epilepsy Society Transitions from Pediatric Epilepsy to Adult Epilepsy Care</a>).</td><td headers="hd_h_nsdhl-dis.T.ck_syndrome_recommended_surv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Starting by age ~10 yrs</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">ADHD = attention-deficit/hyperactivity disorder</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobnsdhldismolgenTA"><div id="nsdhl-dis.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>NSDHL-Related Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_nsdhl-dis.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_nsdhl-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/50814" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>NSDHL</i>
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</a>
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</td><td headers="hd_b_nsdhl-dis.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=50814" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xq28</a>
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</td><td headers="hd_b_nsdhl-dis.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/Q15738" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating</a>
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</td><td headers="hd_b_nsdhl-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.LOVD.nl/NSDHL" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NSDHL @ LOVD</a>
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</td><td headers="hd_b_nsdhl-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=NSDHL" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NSDHL</a>
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</td><td headers="hd_b_nsdhl-dis.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=NSDHL[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NSDHL</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="nsdhl-dis.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="figobnsdhldismolgenTB"><div id="nsdhl-dis.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for NSDHL-Related Disorders (<a href="/omim/300275,300831,308050" 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/NBK51754/table/nsdhl-dis.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.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/300275" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300275</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NAD(P)H STEROID DEHYDROGENASE-LIKE PROTEIN; NSDHL</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/300831" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300831</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CK SYNDROME; CKS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/308050" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">308050</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobnsdhldisTnsdhlpathogenicvariantsre"><div id="nsdhl-dis.T.nsdhl_pathogenic_variants_re" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>NSDHL</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK51754/table/nsdhl-dis.T.nsdhl_pathogenic_variants_re/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__nsdhl-dis.T.nsdhl_pathogenic_variants_re_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_015922.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_015922<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_057006.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_057006<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.262C>T</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg88Ter</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mosaic pathogenic variant identified in male w/CHILD syndrome (See <a href="#nsdhl-dis.Clinical_Description">Clinical Description</a>.)</td></tr><tr><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.455G>A</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly152Asp</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Pathogenic variants identified in persons w/CK syndrome (See <a href="#nsdhl-dis.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>.)</td></tr><tr><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.696_698delGAA</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Lys232del</td></tr><tr><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1098dupT</td><td headers="hd_h_nsdhl-dis.T.nsdhl_pathogenic_variants_re_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg367SerfsTer33</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">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobnsdhldisF1"><div id="nsdhl-dis.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK51754/bin/nsdhl-dis-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Photographs of a female with CHILD syndrome</p><p>A. Upper left limb. Note the forearm hypoplasia, ectrodactyly, onychodystrophy, and characteristic ichthyosiform skin lesions with yellow scales.</p><p>B. Lower left limb and groin. The leg was amputated at the knee to improve function. Note the verruciform xanthoma in the genital region.</p><p>Photographs provided by Dr Amy Paller, Department of Dermatology, Northwestern University School of Medicine</p></div></div></article><article data-type="fig" id="figobnsdhldisF2"><div id="nsdhl-dis.F2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK51754/bin/nsdhl-dis-Image002.jpg" alt="Figure 2. . A male age 11 years (A, B) and a male age 22 years (C,D) with CK syndrome." /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>A male age 11 years (A, B) and a male age 22 years (C,D) with CK syndrome. Note the long thin face, epicanthal folds, almond-shaped palpebral fissures, prominent nasal bridge, and micrognathia. The long thin face becomes more apparent with age.</p></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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