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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Cockayne Syndrome - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Cockayne Syndrome">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2024/08/29">
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<meta name="citation_author" content="Vincent Laugel">
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<meta name="citation_keywords" content="Cockayne Syndrome Type II">
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<meta name="citation_keywords" content="Cockayne Syndrome Type I">
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<meta name="citation_keywords" content="Cockayne Syndrome Type III">
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<meta name="citation_keywords" content="Cerebrooculofacioskeletal (COFS) Syndrome">
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<meta name="citation_keywords" content="DNA excision repair protein ERCC-6">
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<meta name="citation_keywords" content="DNA excision repair protein ERCC-8">
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<meta name="citation_keywords" content="ERCC6">
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<meta name="citation_keywords" content="ERCC8">
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<meta name="citation_keywords" content="Cockayne Syndrome">
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<meta name="DC.Title" content="Cockayne Syndrome">
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<meta name="DC.Contributor" content="Vincent Laugel">
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<meta name="description" content='Cockayne syndrome (referred to as CS in this GeneReview) spans a continuous phenotypic spectrum that includes CS type I, the "classic" or "moderate" form; CS type II, a more severe form with symptoms present at birth (this form overlaps with cerebrooculofacioskeletal [COFS] syndrome); CS type III, a milder and later-onset form; and COFS syndrome, a fetal form of CS.'>
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<meta name="og:description" content='Cockayne syndrome (referred to as CS in this GeneReview) spans a continuous phenotypic spectrum that includes CS type I, the "classic" or "moderate" form; CS type II, a more severe form with symptoms present at birth (this form overlaps with cerebrooculofacioskeletal [COFS] syndrome); CS type III, a milder and later-onset form; and COFS syndrome, a fetal form of CS.'>
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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="_NBK1342_"><span class="title" itemprop="name">Cockayne Syndrome</span></h1><p class="contribs">Laugel V.</p><p class="fm-aai"><a href="#_NBK1342_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 30 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cockayne.Summary" itemprop="description"><h2 id="_cockayne_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Cockayne syndrome (referred to as CS in this <i>GeneReview</i>) spans a continuous phenotypic spectrum that includes CS type I, the "classic" or "moderate" form; CS type II, a more severe form with symptoms present at birth (this form overlaps with cerebrooculofacioskeletal [COFS] syndrome); CS type III, a milder and later-onset form; and COFS syndrome, a fetal form of CS.</p><p>CS type I is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade.</p><p>CS type II is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age five years.</p><p>CS type III is a phenotype in which major clinical features associated with CS only become apparent after age two years; growth and/or cognition exceeds the expectations for CS type I.</p><p>COFS syndrome is characterized by very severe prenatal developmental anomalies (arthrogryposis and microphthalmia).</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of Cockayne syndrome is established in a proband with biallelic pathogenic variants in <i>ERCC6</i> or <i>ERCC8</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Feeding gastrostomy tube placement as needed; individualized educational programs for developmental delay; medications for tremor and spasticity as needed; physical therapy to prevent contractures; use of sunglasses for lens/retina protection; treatment of cataracts and other ophthalmologic complications, hearing loss, hypertension, and gastroesophageal reflux as in the general population; aggressive dental care to minimize dental caries; use of sunscreens and limitation of sun exposure for cutaneous photosensitivity.</p><p><i>Surveillance:</i> Biannual assessment of diet, nervous system, and ophthalmologic status; yearly assessment for complications such as hearing loss, hepatic or renal dysfunction, and hypertension.</p><p><i>Agents/circumstances to avoid:</i> Excessive sun exposure and use of metronidazole. Extra vigilance is needed for opioid and sedative use. Use of growth hormone treatment is not recommended in those with CS.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Cockayne syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CS-related pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CS-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.</p></div></div><div id="cockayne.GeneReview_Scope"><h2 id="_cockayne_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTc"><a href="/books/NBK1342/table/cockayne.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobcockayneTc"><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="cockayne.Tc"><a href="/books/NBK1342/table/cockayne.Tc/?report=objectonly" target="object" rid-ob="figobcockayneTc">Table</a></h4><p class="float-caption no_bottom_margin">CS type I CS type II</p></div></div></div><div id="cockayne.Diagnosis"><h2 id="_cockayne_Diagnosis_">Diagnosis</h2><p>Formal clinical diagnostic criteria originally proposed for Cockayne syndrome (CS) type I [<a class="bibr" href="#cockayne.REF.nance.1992.68" rid="cockayne.REF.nance.1992.68">Nance & Berry 1992</a>] were revised and subsequently expanded [<a class="bibr" href="#cockayne.REF.natale.2011.1081" rid="cockayne.REF.natale.2011.1081">Natale 2011</a>, <a class="bibr" href="#cockayne.REF.laugel.2013.161" rid="cockayne.REF.laugel.2013.161">Laugel 2013</a>]. A diagnostic scoring system has been recently proposed based on both clinical and imaging criteria [<a class="bibr" href="#cockayne.REF.spitz.2021.63" rid="cockayne.REF.spitz.2021.63">Spitz et al 2021</a>].</p><p>Cockayne syndrome is characterized by growth failure and multisystemic involvement, with a variable age of onset and rate of progression. Due to the progressive nature of CS, the clinical diagnosis becomes more certain as additional clinical manifestations gradually evolve over time.</p><p>To facilitate clinical recognition and follow up, the phenotypic spectrum of CS can be divided into different clinical presentations. Note, however, that among all individuals with CS there is a continuous spectrum of clinical severities and that intermediate phenotypes may arise.</p><ul><li class="half_rhythm"><div><b>Cockayne syndrome (CS) type I,</b> "classic" CS, in which the major features of the disease become apparent during early childhood</div></li><li class="half_rhythm"><div><b>Cockayne syndrome (CS) type II,</b> a more severe form with abnormalities recognized at birth or during the neonatal period with early lethality</div></li><li class="half_rhythm"><div><b>Cockayne syndrome (CS) type III,</b> a milder, later-onset form in which major features become apparent during late childhood</div></li><li class="half_rhythm"><div><b>Cerebrooculofacioskeletal (COFS) syndrome,</b> a very severe fetal phenotype with arthrogryposis, prenatal growth failure, congenital microcephaly, and congenital cataracts or microphthalmia</div></li></ul><div id="cockayne.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Cockayne syndrome <b>should be suspected</b> in individuals with the following findings.</p><p>
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<b>Major criteria</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">Postnatal growth failure (height and weight <5th centile by age 2 years)</div></li><li class="half_rhythm"><div class="half_rhythm">Progressive microcephaly and neurologic dysfunction manifested as early developmental delay in most individuals, followed by progressive behavioral and intellectual deterioration in all individuals. Brain MRI reveals white matter dysmyelination and cerebral and cerebellar atrophy [<a class="bibr" href="#cockayne.REF.koob.2010.1623" rid="cockayne.REF.koob.2010.1623">Koob et al 2010</a>, <a class="bibr" href="#cockayne.REF.koob.2016.20151033" rid="cockayne.REF.koob.2016.20151033">Koob et al 2016</a>]. Intracranial calcifications (mainly located in the basal ganglia) are seen in some individuals.</div><div class="half_rhythm">Note: White matter dysmyelination is usually present at disease onset. Cerebral and cerebellar atrophy appear during the course of the disease and worsen over time. Intracranial calcifications may be absent in some individuals, especially during the early stages, but when present typically become more prominent with time.</div></li></ul><p>
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<b>Minor criteria</b>
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</p><ul><li class="half_rhythm"><div>Cutaneous photosensitivity</div></li><li class="half_rhythm"><div>Demyelinating peripheral neuropathy diagnosed by nerve conduction testing</div></li><li class="half_rhythm"><div>Pigmentary retinopathy and/or cataracts</div></li><li class="half_rhythm"><div>Sensorineural hearing loss</div></li><li class="half_rhythm"><div>Dental anomalies including dental caries, enamel hypoplasia, and anomalies of tooth number, size, and shape</div></li><li class="half_rhythm"><div>A characteristic physical appearance of "cachectic dwarfism" with sunken eyes</div></li></ul><p><b>CS type I (classic)</b> is suspected:</p><ul><li class="half_rhythm"><div>In an older child when both major criteria are present and at least three minor criteria are present;</div></li><li class="half_rhythm"><div>In an infant or toddler when both major criteria are present, especially if there is increased cutaneous photosensitivity.</div></li></ul><p><b>CS type II (severe)</b> is suspected:</p><ul><li class="half_rhythm"><div>In infants with growth failure at birth and little postnatal increase in height, weight, or head circumference;</div></li><li class="half_rhythm"><div>When there is little or no postnatal neurologic development;</div></li><li class="half_rhythm"><div>When congenital cataracts are present.</div></li></ul><p><b>CS type III (mild)</b> is suspected:</p><ul><li class="half_rhythm"><div>In children or teenagers with short stature, mild neurologic impairment, and progressive ataxia;</div></li><li class="half_rhythm"><div>Especially but not exclusively when there is cutaneous photosensitivity.</div></li></ul><p><b>COFS syndrome</b> is suspected when prenatal growth failure and congenital microcephaly are associated with arthrogryposis and congenital cataracts as well as other structural defects of the eye (microphthalmia, microcornea, iris hypoplasia).</p></div><div id="cockayne.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Clinical diagnosis.</b> The clinical diagnosis of Cockayne syndrome <b>can be</b>
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<b>established</b> in a proband based on the diagnostic scoring system established by <a class="bibr" href="#cockayne.REF.spitz.2021.63" rid="cockayne.REF.spitz.2021.63">Spitz et al [2021]</a>, which helps define the likelihood of CS and provides guidance on appropriate molecular confirmation.</p><p><b>Molecular diagnosis.</b> The molecular diagnosis of Cockayne syndrome <b>is established</b> in a proband with <a href="#cockayne.Suggestive_Findings">suggestive findings</a> and biallelic pathogenic (or likely pathogenic) variants in one of the genes listed in <a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcockayneTmoleculargenetictestinguse">Table 1</a> identified by molecular genetic testing.</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="#cockayne.REF.richards.2015.405" rid="cockayne.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 biallelic variants of uncertain significance (or of one known pathogenic variant and one variant of uncertain significance) in one of the genes listed in <a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcockayneTmoleculargenetictestinguse">Table 1</a> does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#cockayne.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#cockayne.Option_2">Option 2</a>).</p><div id="cockayne.Option_1"><h4>Option 1</h4><p>When the phenotypic and neuroimaging findings suggest the diagnosis of Cockayne syndrome, molecular genetic testing approaches include use of a <b>multigene panel</b>.</p><p><b>A multigene panel</b> that includes some or all of the genes listed in <a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcockayneTmoleculargenetictestinguse">Table 1</a> and other genes of interest (see <a href="#cockayne.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="cockayne.Option_2"><h4>Option 2</h4><p>When the diagnosis of Cockayne syndrome is not considered because an individual has atypical phenotypic features, <b>comprehensive genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is the best option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. Note: Several pathogenic variants have been detected in the noncoding region of <i>ERCC8</i> that may be detectable by genome sequencing [<a class="bibr" href="#cockayne.REF.laugel.2010.113" rid="cockayne.REF.laugel.2010.113">Laugel et al 2010</a>, <a class="bibr" href="#cockayne.REF.schalk.2018.527" rid="cockayne.REF.schalk.2018.527">Schalk et al 2018</a>].</p><p>Note: If exome sequencing is not diagnostic, an <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.</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="figcockayneTmoleculargenetictestinguse"><a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobcockayneTmoleculargenetictestinguse"><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="cockayne.T.molecular_genetic_testing_use"><a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcockayneTmoleculargenetictestinguse">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Cockayne Syndrome </p></div></div><p><b>DNA repair assay.</b> If the diagnosis of Cockayne syndrome is strongly suspected but molecular genetic testing does not identify pathogenic variants in one of the associated genes, an assay of the cellular phenotype can be considered.</p><p>Assays of DNA repair are performed on skin fibroblasts. The most consistent findings in CS fibroblasts are marked sensitivity to UV radiation and deficient recovery of RNA synthesis following UV damage (i.e., impaired repair of actively transcribed genes, or "transcription-coupled repair") [<a class="bibr" href="#cockayne.REF.nakazawa.2010.506" rid="cockayne.REF.nakazawa.2010.506">Nakazawa et al 2010</a>].</p></div></div></div><div id="cockayne.Clinical_Characteristics"><h2 id="_cockayne_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cockayne.Clinical_Description"><h3>Clinical Description</h3><p>Cockayne syndrome is characterized by growth failure, microcephaly, neurodevelopmental delays, cutaneous photosensitivity, sensorial impairment, and dental anomalies [<a class="bibr" href="#cockayne.REF.laugel.2013.161" rid="cockayne.REF.laugel.2013.161">Laugel 2013</a>].</p><p>Before the molecular genetics of Cockayne syndrome was understood, it was thought to have a single, discrete phenotype: classic Cockayne syndrome. Importantly, it is now recognized that Cockayne syndrome spans a continuous phenotypic spectrum without clear thresholds and includes the following but somewhat arbitrary subtypes [<a class="bibr" href="#cockayne.REF.nance.1992.68" rid="cockayne.REF.nance.1992.68">Nance & Berry 1992</a>]. A quantitative severity scoring system has been designed to account for this continuous spectrum and to help clinicians follow the course of the disease in affected individuals [<a class="bibr" href="#cockayne.REF.spitz.2021.63" rid="cockayne.REF.spitz.2021.63">Spitz et al 2021</a>].</p><ul><li class="half_rhythm"><div>CS type I, the "classic" form</div></li><li class="half_rhythm"><div>CS type II, a more severe form with symptoms present at birth (overlapping with cerebrooculofacioskeletal syndrome [COFS])</div></li><li class="half_rhythm"><div>CS type III, a milder form</div></li><li class="half_rhythm"><div>Cerebrooculofacioskeletal (COFS) syndrome, the most severe end of the phenotypic spectrum of CS, with findings identifiable during fetal life</div></li></ul><p>To date, hundreds of individuals have been identified with Cockayne syndrome and biallelic pathogenic variants in <i>ERCC6</i> or <i>ERCC8</i>. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTcockaynesyndromecomparison"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_comparison/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobcockayneTcockaynesyndromecomparison"><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="cockayne.T.cockayne_syndrome_comparison"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_comparison/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndromecomparison">Table 2. </a></h4><p class="float-caption no_bottom_margin">Cockayne Syndrome: Comparison of Phenotypes by Select Features </p></div></div><div id="cockayne.CS_Type_I"><h4>CS Type I</h4><p><b>Presentation.</b> Prenatal growth is typically normal. Birth length, weight, and head circumference are normal. Within the first two years, however, growth and development fall below normal. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth centile.</p><p><b>Progression.</b> Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability. Brain MRI reveals white matter dysmyelination and progressive cerebral and cerebellar atrophy. Photosensitivity is variable, but individuals are not predisposed to skin cancers.</p><p><b>Additional clinical abnormalities</b> occurring in 10% or more of individuals include the following:</p><ul><li class="half_rhythm"><div><b>Neurologic.</b> Increased tone/spasticity, hyper- or hyporeflexia, stooped standing posture, abnormal gait or inability to walk, ataxia, incontinence, tremor, abnormal or absent speech, seizures, weak cry / poor feeding (as an infant), muscle atrophy, and behavior abnormalities</div></li><li class="half_rhythm"><div><b>Dermatologic.</b> Anhidrosis, malar rash, thin dry hair [<a class="bibr" href="#cockayne.REF.frouin.2013.1414" rid="cockayne.REF.frouin.2013.1414">Frouin et al 2013</a>]</div></li><li class="half_rhythm"><div><b>Ophthalmologic.</b> Enophthalmos, pigmentary retinopathy (60%-100%), abnormal electroretinogram, cataracts of various types (15%-36%), optic atrophy, miotic pupils, decreased or absent tears, strabismus, nystagmus, photophobia, narrowed retinal arterioles</div></li><li class="half_rhythm"><div><b>Hearing.</b> Sensorineural hearing loss</div></li><li class="half_rhythm"><div><b>Dental.</b> Absent or hypoplastic teeth, enamel hypoplasia, delayed eruption of deciduous teeth, and malocclusion. Enamel anomalies frequently lead to severe dental caries [<a class="bibr" href="#cockayne.REF.blochzupan.2013.9" rid="cockayne.REF.blochzupan.2013.9">Bloch-Zupan et al 2013</a>].</div></li><li class="half_rhythm"><div><b>Skeletal.</b> Radiographic findings of thickened calvarium (due to microcephaly), sclerotic epiphyses, vertebral and pelvic abnormalities</div></li><li class="half_rhythm"><div><b>Renal.</b> Abnormal renal function, proteinuria, nephrotic syndrome, hyperuricemia, hypertension [<a class="bibr" href="#cockayne.REF.sterndelfils.2020.103612" rid="cockayne.REF.sterndelfils.2020.103612">Stern-Delfils et al 2020</a>]</div></li><li class="half_rhythm"><div><b>Endocrine.</b> Undescended testes, delayed/absent sexual maturation, diabetes</div></li><li class="half_rhythm"><div><b>Gastrointestinal.</b> Elevated liver function tests, enlargement of liver or spleen, gastroesophageal reflux</div></li></ul><p>Death typically occurs in the first or second decade. The mean age of death is 16 years, although survival into the third decade has been reported [<a class="bibr" href="#cockayne.REF.natale.2011.1081" rid="cockayne.REF.natale.2011.1081">Natale 2011</a>].</p></div><div id="cockayne.CS_Type_II"><h4>CS Type II</h4><p>Children with severe CS have evidence of growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye are present in 30% of individuals. Affected individuals may have some contractures of the spine (kyphosis, scoliosis) and joints in neonatal or early postnatal life. Affected children typically die by age five years [<a class="bibr" href="#cockayne.REF.natale.2011.1081" rid="cockayne.REF.natale.2011.1081">Natale 2011</a>]. CS type II partly overlaps with cerebrooculofacioskeletal (COFS) syndrome.</p></div><div id="cockayne.CS_Type_III"><h4>CS Type III</h4><p>DNA sequencing has confirmed the diagnosis of CS type III in some individuals who have clinical features associated with CS but whose growth and/or cognition exceeds the expectations for CS type I [<a class="bibr" href="#cockayne.REF.natale.2011.1081" rid="cockayne.REF.natale.2011.1081">Natale 2011</a>, <a class="bibr" href="#cockayne.REF.baez.2013.80" rid="cockayne.REF.baez.2013.80">Baez et al 2013</a>]. Major features only become apparent after age two years.</p></div><div id="cockayne.COFS_Syndrome"><h4>COFS Syndrome</h4><p>COFS syndrome is the most severe subtype of the CS spectrum and can be identified during fetal life. Similar to individuals with CS type II, individuals with COFS syndrome present with severe prenatal growth failure, severe developmental delay / intellectual disability from birth, axial hypotonia, peripheral hypertonia, and neonatal feeding difficulties. COFS syndrome is additionally defined by the presence of arthrogryposis and usually the combination of extreme congenital microcephaly and congenital cataracts [<a class="bibr" href="#cockayne.REF.laugel.2008.564" rid="cockayne.REF.laugel.2008.564">Laugel et al 2008</a>].</p><p>COFS syndrome can be recognized during prenatal surveillance and is responsible for cases of spontaneous fetal deaths.</p></div><div id="cockayne.Neuropathology"><h4>Neuropathology</h4><p>In all forms of Cockayne syndrome, a characteristic "tigroid" pattern of demyelination in the subcortical white matter of the brain and multifocal calcium deposition, with relative preservation of neurons and without senile plaques, amyloid, ubiquitin, or tau deposition, has been observed together with arteriosclerosis [<a class="bibr" href="#cockayne.REF.weidenheim.2009.619" rid="cockayne.REF.weidenheim.2009.619">Weidenheim et al 2009</a>, <a class="bibr" href="#cockayne.REF.hayashi.2012.113" rid="cockayne.REF.hayashi.2012.113">Hayashi et al 2012</a>].</p></div></div><div id="cockayne.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>To date no clear genotype-phenotype correlations for <i>ERCC6</i> or <i>ERCC8</i> have been identified. In one study, individuals with pathogenic variants in <i>ERCC8</i> appeared to have significantly less severe manifestations than <i>ERCC6</i> at the time of the diagnosis [<a class="bibr" href="#cockayne.REF.spitz.2021.63" rid="cockayne.REF.spitz.2021.63">Spitz et al 2021</a>].</p><p>For individuals with pathogenic variants in <i>ERCC6</i>, variants upstream of a transposon called PiggyBac transposable element-derived protein 3 in intron 5 of <i>ERCC6</i> were found to be associated with less severe features than pathogenic variants downstream of that transposon insertion [<a class="bibr" href="#cockayne.REF.damajfourcade.2022.762047" rid="cockayne.REF.damajfourcade.2022.762047">Damaj-Fourcade et al 2022</a>].</p></div><div id="cockayne.Nomenclature"><h3>Nomenclature</h3><p>The term "cerebrooculofacioskeletal (COFS) syndrome" and its former synonym, Pena-Shokeir syndrome type II, have been used to refer to a heterogeneous group of disorders characterized by congenital neurogenic arthrogryposis (multiple joint contractures), microcephaly, microphthalmia, and cataracts. The original cases of COFS syndrome, described by <a class="bibr" href="#cockayne.REF.pena.1974.285" rid="cockayne.REF.pena.1974.285">Pena & Shokeir [1974]</a> among First Nations families from Manitoba, have since been shown to be homozygous for a pathogenic variant in <i>ERCC6</i>. COFS syndrome is now regarded as a prenatal form of CS, partly overlapping with CS type II and including the most severe cases of the CS phenotypic spectrum [<a class="bibr" href="#cockayne.REF.laugel.2008.564" rid="cockayne.REF.laugel.2008.564">Laugel et al 2008</a>].</p></div><div id="cockayne.Prevalence"><h3>Prevalence</h3><p>The minimum incidence of CS has been estimated at 2.7 in 1 million births in Western Europe; the disease is probably underdiagnosed [<a class="bibr" href="#cockayne.REF.kleijer.2008.744" rid="cockayne.REF.kleijer.2008.744">Kleijer et al 2008</a>].</p></div></div><div id="cockayne.Genetically_Related_Allelic_Dis"><h2 id="_cockayne_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>Other phenotypes associated with germline pathogenic variants in <i>ERCC6</i> and <i>ERCC8</i> are summarized in <a href="/books/NBK1342/table/cockayne.T.allelic_disorders/?report=objectonly" target="object" rid-ob="figobcockayneTallelicdisorders">Table 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTallelicdisorders"><a href="/books/NBK1342/table/cockayne.T.allelic_disorders/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobcockayneTallelicdisorders"><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="cockayne.T.allelic_disorders"><a href="/books/NBK1342/table/cockayne.T.allelic_disorders/?report=objectonly" target="object" rid-ob="figobcockayneTallelicdisorders">Table 3. </a></h4><p class="float-caption no_bottom_margin">Allelic Disorders </p></div></div></div><div id="cockayne.Differential_Diagnosis"><h2 id="_cockayne_Differential_Diagnosis_">Differential Diagnosis</h2><p>The differential diagnosis of Cockayne syndrome (CS) depends on the presenting features of the individual. Abnormalities that suggest alternative diagnoses include congenital anomalies of the face, limbs, heart, or viscera; recurrent infections (other than otitis media or respiratory infections); metabolic or neurologic crises; hematologic abnormality (e.g., anemia, leukopenia); and cancer of any kind.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTdisorderstoconsiderinthe"><a href="/books/NBK1342/table/cockayne.T.disorders_to_consider_in_the/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobcockayneTdisorderstoconsiderinthe"><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="cockayne.T.disorders_to_consider_in_the"><a href="/books/NBK1342/table/cockayne.T.disorders_to_consider_in_the/?report=objectonly" target="object" rid-ob="figobcockayneTdisorderstoconsiderinthe">Table 4. </a></h4><p class="float-caption no_bottom_margin">Disorders to Consider in the Differential Diagnosis of Cockayne Syndrome </p></div></div><p>Other disorders and acquired conditions include the following:</p><ul><li class="half_rhythm"><div>Profound growth restriction is seen in Dubowitz syndrome (OMIM <a href="https://omim.org/entry/223370" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">223370</a>) and Hallerman-Streiff syndrome (OMIM <a href="https://omim.org/entry/234100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">234100</a>). However, neither disorder is associated with the distinctive physical appearance observed in individuals with CS. The genetic causes of Dubowitz syndrome and Hallerman-Streiff syndrome are unknown.</div></li><li class="half_rhythm"><div>Calcifications on brain imaging can be associated with congenital infections (e.g., rubella or toxoplasmosis) and disorders of calcium and phosphate metabolism. These conditions are distinguished from CS by the absence of white matter abnormalities and the distinctive physical appearance observed in individuals with CS.</div></li><li class="half_rhythm"><div>Growth restriction can also be seen in chromosome disorders and endocrine, metabolic, or gastrointestinal disorders, including malnutrition.</div></li></ul></div><div id="cockayne.Management"><h2 id="_cockayne_Management_">Management</h2><p>No clinical practice guidelines for Cockayne syndrome (CS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.</p><div id="cockayne.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with CS, the evaluations summarized in <a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndromerecommended">Table 5</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="figcockayneTcockaynesyndromerecommended"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobcockayneTcockaynesyndromerecommended"><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="cockayne.T.cockayne_syndrome_recommended"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndromerecommended">Table 5. </a></h4><p class="float-caption no_bottom_margin">Cockayne Syndrome: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="cockayne.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>There is no cure for CS. 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/NBK1342/table/cockayne.T.cockayne_syndrome_treatment_o/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndrometreatmento">Table 6</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTcockaynesyndrometreatmento"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_treatment_o/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobcockayneTcockaynesyndrometreatmento"><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="cockayne.T.cockayne_syndrome_treatment_o"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_treatment_o/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndrometreatmento">Table 6. </a></h4><p class="float-caption no_bottom_margin">Cockayne Syndrome: Treatment of Manifestations </p></div></div><div id="cockayne.Developmental_Delay__Intellectu"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine if any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restricted environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child’s IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters 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="cockayne.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 reassessed 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 individual 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="cockayne.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is 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.</p></div></div><div id="cockayne.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/NBK1342/table/cockayne.T.cockayne_syndrome_recommended_1/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndromerecommended1">Table 7</a> are recommended. Yearly assessment for known potential complications (e.g., hypertension, renal or hepatic dysfunction, declining vision and hearing) is appropriate [<a class="bibr" href="#cockayne.REF.laugel.2013.161" rid="cockayne.REF.laugel.2013.161">Laugel 2013</a>, <a class="bibr" href="#cockayne.REF.wilson.2015.e706" rid="cockayne.REF.wilson.2015.e706">Wilson et al 2015</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTcockaynesyndromerecommended1"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended_1/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobcockayneTcockaynesyndromerecommended1"><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="cockayne.T.cockayne_syndrome_recommended_1"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended_1/?report=objectonly" target="object" rid-ob="figobcockayneTcockaynesyndromerecommended1">Table 7. </a></h4><p class="float-caption no_bottom_margin">Cockayne Syndrome: Recommended Surveillance </p></div></div></div><div id="cockayne.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Excessive sun exposure should be avoided.</p><p>Use of metronidazole should be avoided in any circumstance (risk of severe hepatitis) [<a class="bibr" href="#cockayne.REF.wilson.2015.e706" rid="cockayne.REF.wilson.2015.e706">Wilson et al 2015</a>].</p><p>Extra vigilance is needed for opioid and sedative use due to exaggerated response to these types of medications [<a class="bibr" href="#cockayne.REF.wilson.2016.483" rid="cockayne.REF.wilson.2016.483">Wilson et al 2016</a>].</p><p>Growth hormone (GH) levels in individuals with CS may be elevated or decreased [<a class="bibr" href="#cockayne.REF.park.1994.74" rid="cockayne.REF.park.1994.74">Park et al 1994</a>, <a class="bibr" href="#cockayne.REF.hamamy.2005.875" rid="cockayne.REF.hamamy.2005.875">Hamamy et al 2005</a>]. While individuals with CS do not appear to be at increased risk for malignancy (an effect which may be due to simultaneous transcription and cell proliferation deficiency), it is theoretically possible that GH treatment could reverse this compensatory effect and promote tumor growth. Therefore, in the absence of safety and efficacy data, GH treatment cannot be recommended in individuals with CS.</p></div><div id="cockayne.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#cockayne.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="cockayne.Pregnancy_Management"><h3>Pregnancy Management</h3><p>No individuals with classic or severe CS (types I or II) have been known to reproduce. A successful (but very difficult) pregnancy has been reported in a young woman with mild CS (type III) [<a class="bibr" href="#cockayne.REF.lahiri.2003.871" rid="cockayne.REF.lahiri.2003.871">Lahiri & Davies 2003</a>].</p><p>In pregnant women with CS, the limited size of the pelvis and abdomen is the major obstacle to the growth of the fetus and the major threat to pregnancy outcome. Prevention of premature labor and cesarean section under spinal anesthesia are usually needed [<a class="bibr" href="#cockayne.REF.lahiri.2003.871" rid="cockayne.REF.lahiri.2003.871">Lahiri & Davies 2003</a>, <a class="bibr" href="#cockayne.REF.rawlinson.2003.297" rid="cockayne.REF.rawlinson.2003.297">Rawlinson & Webster 2003</a>].</p></div><div id="cockayne.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. There is currently no therapy that has been proved useful in this disorder.</p></div></div><div id="cockayne.Genetic_Counseling"><h2 id="_cockayne_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="cockayne.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Cockayne syndrome (CS) is inherited in an autosomal recessive manner.</p></div><div id="cockayne.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be heterozygous for an <i>ERCC6</i> or <i>ERCC8</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a CS-related pathogenic variant and to allow reliable recurrence risk assessment.</div></li><li class="half_rhythm"><div>If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#cockayne.REF.j_nsson.2017.519" rid="cockayne.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a CS-related pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Affected sibs will most likely be recognizable as affected within the first few years of life.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Individuals with CS types I or II are not known to reproduce.</div></li><li class="half_rhythm"><div>The offspring of an individual with CS type III are obligate heterozygotes (carriers) for a pathogenic variant in <i>ERCC6</i> or <i>ERCC8.</i></div></li></ul><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>ERCC6</i> or <i>ERCC8</i> pathogenic variant.</p></div><div id="cockayne.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ERCC6</i> or <i>ERCC8</i> pathogenic variants in the family.</p></div><div id="cockayne.Related_Genetic_Counseling_Issu"><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, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing should be considered for the reproductive partners of individuals known to be heterozygous for a CS-related pathogenic variant, particularly if both partners are of the same ancestral background. <i>ERCC6</i> and <i>ERCC8</i> founder variants have been identified in some populations (see <a href="/books/NBK1342/table/cockayne.T.pathogenic_variants_reference/?report=objectonly" target="object" rid-ob="figobcockayneTpathogenicvariantsreference">Table 8</a>).</div></li></ul></div><div id="cockayne.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the CS-causing pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing 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="cockayne.Resources"><h2 id="_cockayne_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>Amy and Friends</b>
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</div><div>United Kingdom</div><div><b>Email:</b> info@amyandfriends.org</div><div>
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<a href="https://www.amyandfriends.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.amyandfriends.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Amy and Friends</b>
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</div><div>Netherlands</div><div>
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<a href="http://www.amyandfriends.nl" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.amyandfriends.nl</a>
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</div></li><li class="half_rhythm"><div>
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<b>Cockayne Syndrome Network</b>
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</div><div><b>Phone:</b> 703-727-0404; 865-466-4634</div><div><b>Email:</b> cockaynesyndrome@gmail.com</div><div>
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<a href="http://cockaynesyndrome.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">cockaynesyndrome.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>L’Association Les P’tits Bouts</b>
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</div><div>France</div><div><b>Phone:</b> 06 81 82 28 03</div><div>
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<a href="https://cockayne.fr/lassociation/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.cockayne.fr/lassociation</a>
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</div></li><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/cockayne-syndrome/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cockayne syndrome</a>
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|
</div></li><li class="half_rhythm"><div>
|
|
<b>NCBI Genes and Disease</b>
|
|
</div><div>
|
|
<a href="/books/NBK22190/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cockayne syndrome</a>
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</div></li><li class="half_rhythm"><div>
|
|
<b>Xeroderma Pigmentosum Society, Inc (XP Society)</b>
|
|
</div><div>
|
|
<i>XP Society has material on their site related to UV protection/avoidance.</i>
|
|
</div><div><b>Phone:</b> 877-XPS-CURE (877-977-2873); 518-851-2612</div><div><b>Email:</b> xps@xps.org</div><div>
|
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<a href="http://www.xps.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.xps.org</a>
|
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</div></li><li class="half_rhythm"><div>
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<b>GenIDA (Genetically determined Intellectual Disabilities and Autism Spectrum Disorders) Registry</b>
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|
</div><div>
|
|
<i>A website for patients, families, and professionals; GenIDA hosts a specific registry for Cockayne syndrome.</i>
|
|
</div><div><b>Email:</b> genida@igbmc.fr</div><div>
|
|
<a href="https://genida.unistra.fr/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.genida.unistra.fr</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Myelin Disorders Bioregistry Project</b>
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|
</div><div><b>Phone:</b> 215-590-1719</div><div><b>Email:</b> sherbinio@chop.edu</div><div>
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|
<a href="https://www.chop.edu/research/myelin-disorders-biorepository-project" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Myelin Disorders Bioregistry Project</a>
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</div></li></ul>
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</div><div id="cockayne.Molecular_Genetics"><h2 id="_cockayne_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="figcockaynemolgenTA"><a href="/books/NBK1342/table/cockayne.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobcockaynemolgenTA"><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="cockayne.molgen.TA"><a href="/books/NBK1342/table/cockayne.molgen.TA/?report=objectonly" target="object" rid-ob="figobcockaynemolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Cockayne Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockaynemolgenTB"><a href="/books/NBK1342/table/cockayne.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobcockaynemolgenTB"><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="cockayne.molgen.TB"><a href="/books/NBK1342/table/cockayne.molgen.TB/?report=objectonly" target="object" rid-ob="figobcockaynemolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Cockayne Syndrome (View All in OMIM) </p></div></div><div id="cockayne.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The proteins encoded by <i>ERCC6</i> and <i>ERCC8</i> both play important roles in transcription-coupled nucleotide excision repair (TC-NER), a DNA repair process that preferentially removes UV-induced pyrimidine dimers and other transcription-blocking lesions from the transcribed strands of active genes.</p><p><i>ERCC6</i> encodes DNA excision repair protein ERCC-6, which has at least seven domains that are conserved in DNA and RNA helicases. This protein appears to enhance the elongation of transcription products by RNA polymerase II, and possibly also RNA polymerases I and III.</p><p><i>ERCC8</i> encodes DNA excision repair protein ERCC-8, which is a WD repeat (tryptophan aspartate repeats) protein component of a large cullin4-mediated E3 ubiquitin ligase complex.</p><p>A deficiency of TC-NER is sufficient to explain the cutaneous photosensitivity of individuals with CS. It is unlikely, however, to explain the growth failure and neurodegeneration that typify CS. In contrast to CS, most individuals with <a href="/books/n/gene/xp/?report=reader">xeroderma pigmentosum</a> (XP) have normal growth and neurologic function, despite having combined deficiencies of both TC-NER and global genome nucleotide excision repair (GG-NER). To explain this apparent paradox, it has been suggested that CS proteins have other functions, including roles in transcription reinitiation after genotoxic stress [<a class="bibr" href="#cockayne.REF.epanchintsev.2017.1054" rid="cockayne.REF.epanchintsev.2017.1054">Epanchintsev et al 2017</a>], repair of oxidative DNA damage [<a class="bibr" href="#cockayne.REF.nardo.2009.6209" rid="cockayne.REF.nardo.2009.6209">Nardo et al 2009</a>, <a class="bibr" href="#cockayne.REF.ranes.2016.5246" rid="cockayne.REF.ranes.2016.5246">Ranes et al 2016</a>], and mitochondrial metabolism [<a class="bibr" href="#cockayne.REF.kamenisch.2013.270" rid="cockayne.REF.kamenisch.2013.270">Kamenisch & Berneburg 2013</a>, <a class="bibr" href="#cockayne.REF.chatre.2015.e2910" rid="cockayne.REF.chatre.2015.e2910">Chatre et al 2015</a>, <a class="bibr" href="#cockayne.REF.scheibyeknudsen.2016.12502" rid="cockayne.REF.scheibyeknudsen.2016.12502">Scheibye-Knudsen et al 2016</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcockayneTpathogenicvariantsreference"><a href="/books/NBK1342/table/cockayne.T.pathogenic_variants_reference/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figobcockayneTpathogenicvariantsreference"><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="cockayne.T.pathogenic_variants_reference"><a href="/books/NBK1342/table/cockayne.T.pathogenic_variants_reference/?report=objectonly" target="object" rid-ob="figobcockayneTpathogenicvariantsreference">Table 8. </a></h4><p class="float-caption no_bottom_margin">Pathogenic Variants Referenced in This <i>GeneReview</i> by Gene </p></div></div></div></div><div id="cockayne.Chapter_Notes"><h2 id="_cockayne_Chapter_Notes_">Chapter Notes</h2><div id="cockayne.Author_Notes"><h3>Author Notes</h3><p>Vincent Laugel (<a href="mailto:dev@null" data-email="rf.gruobsarts-urhc@legual.tnecniv" class="oemail">rf.gruobsarts-urhc@legual.tnecniv</a>) is actively involved in clinical research regarding individuals with Cockayne syndrome (CS). He would be happy to communicate with persons who have any questions regarding diagnosis of CS or other considerations.</p><p>Dr Laugel is also interested in hearing from clinicians treating families affected by DNA repair and transcription disorders in whom no causative variant has been identified through molecular genetic testing of the genes known to be involved in this group of disorders.</p><p>Contact Dr Laugel to inquire about review of <i>ERCC6</i> and <i>ERCC8</i> variants of uncertain significance.</p></div><div id="cockayne.Acknowledgements"><h3>Acknowledgements</h3><p>The author wishes to thank "Amy and friends" and "Les P'tits Bouts" family support groups for continuous support.</p></div><div id="cockayne.Author_History"><h3>Author History</h3><p>Vincent Laugel, MD, PhD (2012-present)<br />Martha A Nance, MD; Park Nicollet Clinic (2000-2006) <br />Edward G Neilan, MD, PhD; Children's Hospital Boston (2006-2012)</p></div><div id="cockayne.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>29 August 2024 (gm) Comprehensive update posted live</div></li><li class="half_rhythm"><div>29 August 2019 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 June 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 March 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>31 July 2003 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>28 December 2000 (me) Review posted live</div></li><li class="half_rhythm"><div>June 2000 (mn) Original submission</div></li></ul></div></div><div id="cockayne.References"><h2 id="_cockayne_References_">References</h2><div id="cockayne.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="cockayne.REF.baer.2021.104105">Baer
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[<a href="https://pubmed.ncbi.nlm.nih.gov/19647012" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19647012</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cockayne.REF.wilson.2016.483">Wilson
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BT, Stark
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Z, Sutton
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RE, Danda
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S, Ekbote
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AV, Elsayed
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SM, Gibson
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L, Goodship
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JA, Jackson
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AP, Keng
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WT, King
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MD, McCann
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E, Motojima
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T, Murray
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JE, Omata
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T, Pilz
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D, Pope
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K, Sugita
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K, White
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SM, Wilson
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IJ. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care.
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Genet Med.
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2016;18:483-93.
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[<a href="/pmc/articles/PMC4857186/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4857186</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26204423" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26204423</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cockayne.REF.wilson.2015.e706">Wilson
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BT, Strong
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A, O'Kelly
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S, Munkley
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J, Stark
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Z. Metronidazole toxicity in Cockayne syndrome: a case series.
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Pediatrics.
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2015;136:e706-8.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/26304821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26304821</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1342_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Vincent Laugel</span>, MD, PhD<div class="affiliation small">Laboratory of Medical Genetics<br />Strasbourg, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="rf.gruobsarts-urhc@legual.tnecniv" class="oemail">rf.gruobsarts-urhc@legual.tnecniv</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">December 28, 2000</span>; Last Update: <span itemprop="dateModified">August 29, 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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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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hereby granted to reproduce, distribute, and translate copies of content materials for
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noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
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of GeneReviews chapters for use in lab reports and clinic notes are a permitted
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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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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>Laugel V. Cockayne Syndrome. 2000 Dec 28 [Updated 2024 Aug 29]. 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/ccd/?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/coffin-siris/?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="figobcockayneTc"><div id="cockayne.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cockayne Syndrome (CS): Phenotypic Spectrum</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>CS type I</div></li><li class="half_rhythm"><div>CS type II</div></li><li class="half_rhythm"><div>CS type III</div></li><li class="half_rhythm"><div>Cerebrooculofacioskeletal (COFS) 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="#cockayne.Nomenclature">Nomenclature</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTmoleculargenetictestinguse"><div id="cockayne.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Cockayne Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1, 2</sup></th><th id="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of Cockayne Syndrome Attributed to Pathogenic Variants in Gene</th><th id="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>3</sup> Identified by Method</th></tr><tr><th headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3" id="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></th><th headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3" id="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC6</i>
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</td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~65%</td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3 hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90% <sup>6</sup></td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3 hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10% <sup>6</sup></td></tr><tr><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC8</i>
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</td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~35%</td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3 hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">88% <sup>6</sup></td><td headers="hd_h_cockayne.T.molecular_genetic_testing_use_1_1_1_3 hd_h_cockayne.T.molecular_genetic_testing_use_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12% <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cockayne.TF.1.1"><p class="no_margin">Genes are listed in alphabetic order.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cockayne.TF.1.2"><p class="no_margin">See <a href="/books/NBK1342/?report=reader#cockayne.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cockayne.TF.1.3"><p class="no_margin">See <a href="#cockayne.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="cockayne.TF.1.4"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include 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>5. </dt><dd><div id="cockayne.TF.1.5"><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>6. </dt><dd><div id="cockayne.TF.1.6"><p class="no_margin"><a class="bibr" href="#cockayne.REF.laugel.2010.113" rid="cockayne.REF.laugel.2010.113">Laugel et al [2010]</a>, <a class="bibr" href="#cockayne.REF.calmels.2018.329" rid="cockayne.REF.calmels.2018.329">Calmels et al [2018]</a>, and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#cockayne.REF.stenson.2020.1197" rid="cockayne.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTcockaynesyndromecomparison"><div id="cockayne.T.cockayne_syndrome_comparison" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Cockayne Syndrome: Comparison of Phenotypes by Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_comparison/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.cockayne_syndrome_comparison_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CS Type I</th><th id="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CS Type II</th><th id="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CS Type III</th><th id="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">COFS Syndrome</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Typical age of onset</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early childhood (age <2 years)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At birth (severe)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late childhood (age >2 years)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">During fetal life</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth failure</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prenatal growth normal; onset of growth failure age <2 years</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset at birth</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late childhood (age >2 years)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset during fetal life</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Photosensitivity</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinically variable</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinically variable</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinically variable</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinically variable</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision issues</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cataracts, pigmentary retinopathy, optic atrophy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital cataracts , pigmentary retinopathy, optic atrophy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cataracts, pigmentary retinopathy, optic atrophy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital cataracts, pigmentary retinopathy, optic atrophy</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing issues</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurosensorial hearing loss</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurosensorial hearing loss</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurosensorial hearing loss</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurosensorial hearing loss</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic abnormalities</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay, intellectual disability, cerebellar ataxia, spasticity, peripheral neuropathy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe developmental delay, severe intellectual disability, cerebellar ataxia, spasticity, peripheral neuropathy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intellectual disability, dementia, cerebellar ataxia, spasticity, peripheral neuropathy</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arthrogryposis, severe developmental delay, cerebellar ataxia, spasticity, peripheral neuropathy</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin cancer predisposition</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Progression</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progresses throughout childhood</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Almost no psychomotor development</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progresses throughout childhood & adulthood</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Almost no psychomotor development</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Prognosis</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Death during 1st or 2nd decade (mean age 16 years)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Death usually in 1st decade but prolonged survival possible in a few cases</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Long-term survival into adulthood</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Death usually in 1st decade but prolonged survival possible in a few cases</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Typical facial appearance ("cachectic dwarfism" w/sunken eyes)</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Present in early life</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Present in early life</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May appear progressively in late stages</td><td headers="hd_h_cockayne.T.cockayne_syndrome_comparison_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinct morphologic features w/prominent nasal root & prominent metopic suture; no clear cachectic appearance in most cases</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">COFS = cerebrooculofacioskeletal syndrome; CS = Cockayne syndrome</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Based on <a class="bibr" href="#cockayne.REF.laugel.2013.161" rid="cockayne.REF.laugel.2013.161">Laugel [2013]</a>, <a class="bibr" href="#cockayne.REF.wilson.2016.483" rid="cockayne.REF.wilson.2016.483">Wilson et al [2016]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTallelicdisorders"><div id="cockayne.T.allelic_disorders" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Allelic Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.allelic_disorders/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.allelic_disorders_lrgtbl__"><table><thead><tr><th id="hd_h_cockayne.T.allelic_disorders_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_cockayne.T.allelic_disorders_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cockayne.T.allelic_disorders_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC6</i>
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</td><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UV-sensitive syndrome 1</td><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/600630" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">600630</a></td></tr><tr><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Premature ovarian failure (reported in 1 study)</td><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a class="bibr" href="#cockayne.REF.qin.2015.e1005419" rid="cockayne.REF.qin.2015.e1005419">Qin et al [2015]</a>
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</td></tr><tr><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC8</i>
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</td><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UV-sensitive syndrome 2</td><td headers="hd_h_cockayne.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/614621" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614621</a></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcockayneTdisorderstoconsiderinthe"><div id="cockayne.T.disorders_to_consider_in_the" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Disorders to Consider in the Differential Diagnosis of Cockayne Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.disorders_to_consider_in_the/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.disorders_to_consider_in_the_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Key Feature(s) Overlapping w/CS</th><th id="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Features</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PLP1</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe "connatal" Pelizaeus-Merzbacher disease (See <a href="/books/n/gene/pmd/?report=reader"><i>PLP1</i> Disorders</a>.) <sup>1</sup></td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">White matter abnormalities & growth restriction</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe growth failure & distinctive physical appearance in CS</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATR</i><br /><i>CPAP</i> (<i>CENPJ</i>)<br /><i>CEP152</i><br /><i>CEP63</i><br /><i>DNA2</i><br /><i>NSMCE2</i><br /><i>RBBP8</i> (<i>CTIP</i>)<br /><i>TRAIP</i></td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seckel syndrome (OMIM <a href="https://omim.org/phenotypicSeries/PS210600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS210600</a>)</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Profound growth restriction</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Distinctive physical appearance in CS</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BRD4</i>
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<br />
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<i>HDAC8</i>
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<br />
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<i>NIPBL</i>
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<br />
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<i>RAD21</i>
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<br />
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<i>SMC1A</i>
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<br />
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<i>SMC3</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cdls/?report=reader">Cornelia de Lange syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />XL</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CREBBP</i>
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<br />
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<i>EP300</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rsts/?report=reader">Rubinstein-Taybi syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLR3A</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wiedemann-Rautenstrauch syndrome (OMIM <a href="https://omim.org/entry/264090" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">264090</a>)</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genetically heterogeneous <sup>2</sup></td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rss/?report=reader">Silver-Russell syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 2.</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ANAPC1</i>
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<br />
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<i>RECQL4</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rts/?report=reader">Rothmund-Thompson syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Prominent photosensitivity &/or thinning of skin & hair</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">White matter abnormalities, brain calcifications, ataxia, spasticity, & neurodegenerative features in CS</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BLM</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/bloom/?report=reader">Bloom syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DDB2</i>
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<br />
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<i>ERCC1</i>
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<br />
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<i>ERCC2</i>
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<br />
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<i>ERCC3</i>
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<br />
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<i>ERCC4</i>
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<br />
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<i>ERCC5</i>
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<br />
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<i>POLH</i>
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<br />
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<i>XPA</i>
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<br />
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<i>XPC</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/xp/?report=reader">Xeroderma pigmentosum</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>LMNA</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hgps/?report=reader">Hutchinson-Gilford progeria syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>WRN</i>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/werner/?report=reader">Werner syndrome</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>350 genes <sup>3</sup></td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mt-overview/?report=reader">Primary mitochondrial disorders</a>
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</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR<br />Mat<br />XL</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early presence of pigmentary retinopathy, brain calcifications, & neurodegeneration</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin photosensitivity & distinctive physical appearance in CS</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>RAB3GAP1</i>
|
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<br />
|
|
<i>RAB3GAP2</i>
|
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<br />
|
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<i>RAB18</i>
|
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<br />
|
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<i>TBC1D20</i>
|
|
</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/rab18-def/?report=reader">RAB18 deficiency</a> (molecular deficit underlying both Warburg micro syndrome & Martsolf syndrome)</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Microcephaly, microcornea, & cataracts (RAB18 deficiency may resemble CS type II / COFS syndrome at birth)</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RAB18 deficiency is not assoc w/rapidly progressive neurodegeneration & has normal DNA nucleotide excision repair.</td></tr><tr><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MORC2</i>
|
|
</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MORC2</i>-related disorder <sup>4</sup></td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical presentation is very similar to CS in some persons & can incl microcephaly, growth restriction, & neurodevelopmental delays.</td><td headers="hd_h_cockayne.T.disorders_to_consider_in_the_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal DNA nucleotide excision repair & no skin photosensitivity</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; COFS = cerebrooculofacioskeletal syndrome; CS = Cockayne syndrome; Mat = maternal; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cockayne.TF.4.1"><p class="no_margin">Most leukodystrophies are not associated with growth restriction, with the exception of the severe or "connatal" form of Pelizaeus-Merzbacher disease, in which children may have short stature and poor weight gain.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cockayne.TF.4.2"><p class="no_margin">Genetic testing confirms clinical diagnosis in approximately 60% of affected individuals. Hypomethylation of the imprinted control region 1 (ICR1) at 11p15.5 causes Silver-Russell syndrome (SRS) in 35%-50% of individuals, and maternal uniparental disomy causes SRS in 7%-10% of individuals. Accurate assessment of SRS recurrence requires identification of the causative genetic mechanism in the proband.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cockayne.TF.4.3"><p class="no_margin">
|
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<a class="bibr" href="#cockayne.REF.mccormick.2018.714" rid="cockayne.REF.mccormick.2018.714">McCormick et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="cockayne.TF.4.4"><p class="no_margin"><a class="bibr" href="#cockayne.REF.mirchi.2022.271" rid="cockayne.REF.mirchi.2022.271">Mirchi et al [2022]</a>, <a class="bibr" href="#cockayne.REF.stafki.2023.79" rid="cockayne.REF.stafki.2023.79">Stafki et al [2023]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTcockaynesyndromerecommended"><div id="cockayne.T.cockayne_syndrome_recommended" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Cockayne Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.cockayne_syndrome_recommended_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/<br />Concern</th><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measure & plot growth on appropriate growth charts.</div></li><li class="half_rhythm"><div>Appropriately assess feeding & nutritional status according to specific curves.</div></li></ul>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Specific growth curves have been designed for CS types I & II. <sup>1</sup></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_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_cockayne.T.cockayne_syndrome_recommended_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_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Brain MRI</div></li><li class="half_rhythm"><div>Neurologic eval incl assessment of muscle tone</div></li></ul>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
|
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possibly incl electroretinogram</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl audiogram</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dermatologic eval</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Teeth</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental eval</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Radiographs to document skeletal dysplasia if suggestive clinical signs are present</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Kidneys</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laboratory eval of renal function</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Liver</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laboratory eval of liver function</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_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_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval for hypertension</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
|
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of CS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
|
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<br />
|
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<b>& resources</b>
|
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By clinicians, wider care team, & family support organizations</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#cockayne.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a></div></li><li class="half_rhythm"><div>Social work involvement for parental support</div></li><li class="half_rhythm"><div>Home nursing referral</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CS = Cockayne syndrome; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cockayne.TF.5.1"><p class="no_margin">
|
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<a class="bibr" href="#cockayne.REF.baer.2021.104105" rid="cockayne.REF.baer.2021.104105">Baer et al [2021]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cockayne.TF.5.2"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTcockaynesyndrometreatmento"><div id="cockayne.T.cockayne_syndrome_treatment_o" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Cockayne Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_treatment_o/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.cockayne_syndrome_treatment_o_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Poor growth</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Feeding support</div></li><li class="half_rhythm"><div>Gastrostomy tube placement as needed. Note: Avoid rapid ↑ in volume of feeds.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Developmental delay /</b>
|
|
<br />
|
|
<b>Intellectual disability</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#cockayne.Developmental_Delay__Intellectu">Developmental Delay / Intellectual Disability Management Issues</a>.</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Tremor</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider treatment of tremor (carbidopa-levodopa <sup>1</sup>) & spasticity (baclofen) if needed.</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Spasticity</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PT to prevent joint contractures</div></li><li class="half_rhythm"><div>Home safety assessments to prevent falls</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Abnormal vision &/or cataracts</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Standard treatment(s) per ophthalmologist</div></li><li class="half_rhythm"><div>Use of sunglasses for lens & retina protection</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing loss</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hearing aids may be helpful per otolaryngologist.</div></li><li class="half_rhythm"><div>Cochlear implants may be used. <sup>2</sup></div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Dental caries</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Aggressive dental care to minimize caries</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Cutaneous photosensitivity</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use of sunscreens & limitation of sun exposure</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Hypertension</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Amlodipine, ACE inhibitor</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastroesophageal reflux</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_treatment_o_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proton pump inhibitor</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">PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cockayne.TF.6.1"><p class="no_margin">
|
|
<a class="bibr" href="#cockayne.REF.neilan.2008.1117" rid="cockayne.REF.neilan.2008.1117">Neilan et al [2008]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cockayne.TF.6.2"><p class="no_margin">
|
|
<a class="bibr" href="#cockayne.REF.van_wyhe.2018.64" rid="cockayne.REF.van_wyhe.2018.64">Van Wyhe et al [2018]</a>
|
|
</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcockayneTcockaynesyndromerecommended1"><div id="cockayne.T.cockayne_syndrome_recommended_1" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Cockayne Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.cockayne_syndrome_recommended_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.cockayne_syndrome_recommended_1_lrgtbl__"><table><thead><tr><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Nutritional status & growth</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dietary assessment</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Every 6 mos or as clinically indicated</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval of gait, tone, & overall neurologic functioning</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Eye</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic assessment (eval for cataracts & retinopathy)</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6 mos until age 4 yrs, then annually</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing assessment</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_3" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as clinically indicated</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Diabetes</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Blood glucose</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Liver function</b>
|
|
</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver enzymes</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Kidney</b>
|
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Kidney function; uric acid & proteinuria</td></tr><tr><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiovascular</b>
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</td><td headers="hd_h_cockayne.T.cockayne_syndrome_recommended_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Blood pressure</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcockaynemolgenTA"><div id="cockayne.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Cockayne Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cockayne.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cockayne.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cockayne.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cockayne.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cockayne.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cockayne.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cockayne.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/2074" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>ERCC6</i>
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</a>
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</td><td headers="hd_b_cockayne.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=2074" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">10q11<wbr style="display:inline-block"></wbr>​.23</a>
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</td><td headers="hd_b_cockayne.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/Q03468" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA excision repair protein ERCC-6</a>
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</td><td headers="hd_b_cockayne.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/ERCC6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC6 database</a>
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</td><td headers="hd_b_cockayne.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=ERCC6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC6</a>
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</td><td headers="hd_b_cockayne.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=ERCC6[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC6</a>
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</td></tr><tr><td headers="hd_b_cockayne.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/1161" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>ERCC8</i>
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</a>
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</td><td headers="hd_b_cockayne.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=1161" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">5q12<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_b_cockayne.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/Q13216" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA excision repair protein ERCC-8</a>
|
|
</td><td headers="hd_b_cockayne.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/ERCC8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC8 database</a>
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</td><td headers="hd_b_cockayne.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=ERCC8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC8</a>
|
|
</td><td headers="hd_b_cockayne.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=ERCC8[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC8</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="cockayne.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
|
|
<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="figobcockaynemolgenTB"><div id="cockayne.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Cockayne Syndrome (<a href="/omim/133540,216400,609412,609413" 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/NBK1342/table/cockayne.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.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/133540" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">133540</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COCKAYNE SYNDROME B; CSB</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/216400" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">216400</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COCKAYNE SYNDROME A; CSA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/609412" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">609412</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 8, CSA UBIQUITIN LIGASE COMPLEX SUBUNIT; ERCC8</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/609413" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">609413</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 6, CHROMATIN REMODELING FACTOR; ERCC6</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcockayneTpathogenicvariantsreference"><div id="cockayne.T.pathogenic_variants_reference" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p>Pathogenic Variants Referenced in This <i>GeneReview</i> by Gene</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1342/table/cockayne.T.pathogenic_variants_reference/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cockayne.T.pathogenic_variants_reference_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<br />
|
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<i>ERCC6</i>
|
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</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000124.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000124<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_000115.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000115<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1034_1035insT</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Lys345AsnfsTer24</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in <a href="/books/n/gene/founder_druze/?report=reader">Druze population</a></td></tr><tr><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.3862C>T</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg1288Ter</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/COFS; founder variant in Finnish population [<a class="bibr" href="#cockayne.REF.jaakkola.2010.541" rid="cockayne.REF.jaakkola.2010.541">Jaakkola et al 2010</a>, <a class="bibr" href="#cockayne.REF.laugel.2010.113" rid="cockayne.REF.laugel.2010.113">Laugel et al 2010</a>]</td></tr><tr><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2709+1G>T</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in <a href="/books/n/gene/founder_amish/?report=reader">Amish population</a></td></tr><tr><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ERCC8</i>
|
|
</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000082.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000082<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_000073.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000073<wbr style="display:inline-block"></wbr>​.1</a>
|
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</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.966C>A</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr322Ter</td><td headers="hd_h_cockayne.T.pathogenic_variants_reference_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Arab population [<a class="bibr" href="#cockayne.REF.khayat.2010.3091" rid="cockayne.REF.khayat.2010.3091">Khayat et al 2010</a>, <a class="bibr" href="#cockayne.REF.chebly.2018.161" rid="cockayne.REF.chebly.2018.161">Chebly et al 2018</a>]</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 author. <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 class="bkr_refwrap"><dt>1. </dt><dd><div id="cockayne.TF.8.1"><p class="no_margin">Genes from <a href="/books/NBK1342/table/cockayne.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcockayneTmoleculargenetictestinguse">Table 1</a> are in alphabetic order.</p></div></dd></dl></dl></div></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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