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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2022/10/13">
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<meta name="citation_author" content="Luba Kalaydjieva">
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<meta name="citation_author" content="Teodora Chamova">
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<meta name="citation_keywords" content="CTDP1-CCFDN">
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<meta name="citation_keywords" content="CTDP1-CCFDN">
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<meta name="citation_keywords" content="RNA polymerase II subunit A C-terminal domain phosphatase">
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<meta name="citation_keywords" content="CTDP1">
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<meta name="citation_keywords" content="CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy">
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<meta name="DC.Title" content="CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Luba Kalaydjieva">
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<meta name="DC.Contributor" content="Teodora Chamova">
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<meta name="DC.Date" content="2022/10/13">
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<meta name="description" content="CTDP1-related congenital cataracts, facial dysmorphism, and neuropathy (CTDP1-CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils), mildly dysmorphic facial features apparent in late childhood, and a hypo-/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade of life. Secondary foot deformities and scoliosis are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild nonprogressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and most have subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Romani population.">
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<meta name="og:description" content="CTDP1-related congenital cataracts, facial dysmorphism, and neuropathy (CTDP1-CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils), mildly dysmorphic facial features apparent in late childhood, and a hypo-/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade of life. Secondary foot deformities and scoliosis are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild nonprogressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and most have subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Romani population.">
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id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" 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="_NBK25565_"><span class="title" itemprop="name"><i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>CTDP1</i>-CCFDN</div><p class="contribs">Kalaydjieva L, Chamova T.</p><p class="fm-aai"><a href="#_NBK25565_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 25 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="ccfdn.Summary" itemprop="description"><h2 id="_ccfdn_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils), mildly dysmorphic facial features apparent in late childhood, and a hypo-/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade of life. Secondary foot deformities and scoliosis are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild nonprogressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and most have subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Romani population.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>CTDP1</i>-CCFDN is established in a proband by identification of biallelic pathogenic variants in <i>CTDP1</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Cataracts are treated surgically; exaggerated inflammatory response and foreign-body reaction to contact lenses and intraocular lenses warrant close postoperative follow up. Peripheral neuropathy is managed symptomatically in the usual manner. Secondary spine and foot deformities may require surgical intervention. Developmental services and educational support as needed. Management of cerebellar manifestations per physical medicine / rehabilitation / physical and occupational therapists. Close postoperative monitoring for risk of anesthetic complications. Hormone replacement therapy for hypogonadotropic hypogonadism may help prevent osteoporosis in females. Awareness of rhabdomyolysis as a potential complication following febrile infections in order to seek medical attention with the first recognizable symptoms and to provide oral corticosteroid treatment (for 2-3 weeks for optimal recovery).</p><p><i>Surveillance:</i> Annual examinations for possible ophthalmologic, neurologic, and endocrine manifestations. Developmental assessments throughout childhood.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early initiation of treatment of ophthalmologic, neurologic, and endocrine manifestations.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>CTDP1</i>-CCFDN is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a <i>CTDP1</i> 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 <i>CTDP1</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members and prenatal/preimplantation genetic testing are possible.</p></div></div><div id="ccfdn.Diagnosis"><h2 id="_ccfdn_Diagnosis_">Diagnosis</h2><div id="ccfdn.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) <b>should be suspected</b> in individuals with the following clinical findings:</p><ul><li class="half_rhythm"><div>Bilateral congenital cataracts, microcornea, and micropupils</div></li><li class="half_rhythm"><div>Mildly dysmorphic facial features apparent from late childhood (prominent midface with a well-developed nose, thickening of the perioral tissues, forwardly directed anterior dentition, and micrognathia)</div></li><li class="half_rhythm"><div>Hypo-/demyelinating peripheral neuropathy</div></li><li class="half_rhythm"><div>Mild nonprogressive intellectual deficit</div></li><li class="half_rhythm"><div>Intrauterine growth restriction with subsequent small stature and subnormal weight in adulthood</div></li></ul><p>Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="ccfdn.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>CTDP1</i>-CCFDN is <b>established</b> in a proband by identification of biallelic pathogenic (or likely pathogenic) variants in <i>CTDP1</i> on molecular genetic testing (see <a href="/books/NBK25565/table/ccfdn.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobccfdnTmoleculargenetictestingusedi">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#ccfdn.REF.richards.2015.405" rid="ccfdn.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>CTDP1</i> variants of uncertain significance (or of one known <i>CTDP1</i> pathogenic variant and one <i>CTDP1</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include <b>targeted analysis of a pathogenic variant</b> and <b>single-gene testing</b>:</p><ul><li class="half_rhythm"><div><b>Targeted analysis</b> of the pathogenic variant <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> (also known as IVS6+389C>T) can be performed first in individuals of Romani ancestry. To date, all affected individuals and carriers identified have been from the Romani population.</div></li><li class="half_rhythm"><div><b>Single-gene testing.</b> Sequence analysis of <i>CTDP1</i> may be considered to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</div></li></ul><p>Note: (1) Although other <i>CTDP1</i> pathogenic variants may cause CCFDN, no additional variants other than <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> have been reported to date. (2) c.863+389C>T reduces but does not abolish CTDP1 protein expression (see <a href="#ccfdn.Molecular_Genetics">Molecular Genetics</a>). It is not known if complete loss of CTDP1 results in different clinical features or is compatible with life.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTmoleculargenetictestingusedi"><a href="/books/NBK25565/table/ccfdn.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobccfdnTmoleculargenetictestingusedi"><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="ccfdn.T.molecular_genetic_testing_used_i"><a href="/books/NBK25565/table/ccfdn.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobccfdnTmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy </p></div></div></div></div><div id="ccfdn.Clinical_Characteristics"><h2 id="_ccfdn_Clinical_Characteristics_">Clinical Characteristics</h2><div id="ccfdn.Clinical_Description"><h3>Clinical Description</h3><p><i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) is a complex disorder whose major manifestations involve the anterior segment of the eye, the skull and face, the nervous system, and the endocrine system [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.tournev.1999b.165" rid="ccfdn.REF.tournev.1999b.165">Tournev et al 1999b</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>, <a class="bibr" href="#ccfdn.REF.lassuthova.2014.46" rid="ccfdn.REF.lassuthova.2014.46">Lassuthova et al 2014</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. To date, 190 individuals have been identified with a pathogenic variant in <i>CTDP1</i> [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>, <a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>, <a class="bibr" href="#ccfdn.REF.cordelli.2010.343" rid="ccfdn.REF.cordelli.2010.343">Cordelli et al 2010</a>, <a class="bibr" href="#ccfdn.REF.lassuthova.2014.46" rid="ccfdn.REF.lassuthova.2014.46">Lassuthova et al 2014</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>, <a class="bibr" href="#ccfdn.REF.hudec.2022.4207" rid="ccfdn.REF.hudec.2022.4207">Hudec et al 2022</a>]. The following description of the phenotypic features associated with <i>CTDP1</i>-CCFDN is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTctdp1relatedcongenitalcataract"><a href="/books/NBK25565/table/ccfdn.T.ctdp1related_congenital_cataract/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobccfdnTctdp1relatedcongenitalcataract"><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="ccfdn.T.ctdp1related_congenital_cataract"><a href="/books/NBK25565/table/ccfdn.T.ctdp1related_congenital_cataract/?report=objectonly" target="object" rid-ob="figobccfdnTctdp1relatedcongenitalcataract">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy: Frequency of Select Features </p></div></div><div id="ccfdn.Ocular_Manifestations"><h4>Ocular Manifestations</h4><p>Congenital cataracts are the invariable first manifestation of <i>CTDP1</i>-CCFDN [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>]. The cataracts are bilateral and can appear as anterior or posterior subcapsular opacities with clouding of the adjacent part of the lens nucleus or as total cataracts involving the entire lens [<a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>].</p><p>Other ocular manifestations include microcornea, microphthalmia (documented by axial length measurements), and micropupils with fibrotic margins, showing sluggish constriction to light and dilation to mydriatics [<a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>].</p><p>Horizontal pendular nystagmus is very common [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>] and unrelated to the visual defect caused by the cataracts.</p><p>No fundus abnormalities are present.</p></div><div id="ccfdn.Facial_Features"><h4>Facial Features</h4><p>Dysmorphic facial features become apparent in late childhood and are particularly evident in adult males. They include a prominent midface with a well-developed nose, thickening of the perioral tissues, forwardly directed anterior dentition, and micrognathia [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>].</p></div><div id="ccfdn.Nervous_System"><h4>Nervous System</h4><p><b>Hypomyelinating peripheral neuropathy</b> is symmetric and distally accentuated, with predominantly motor involvement progressing to severe disability by the third decade of life. In a study of 28 affected children ages four months to 16 years, <a class="bibr" href="#ccfdn.REF.kalaydjieva.2005.65" rid="ccfdn.REF.kalaydjieva.2005.65">Kalaydjieva et al [2005]</a> observed an invariable delay in early motor development, with all starting to walk between ages two and three years, often with an unsteady gait. Clinical signs of lower-limb motor peripheral neuropathy (diminished or absent tendon reflexes, distal lower-limb weakness, and foot deformities) become apparent after age four years and are soon followed by involvement of the upper limbs [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>, <a class="bibr" href="#ccfdn.REF.kalaydjieva.2005.65" rid="ccfdn.REF.kalaydjieva.2005.65">Kalaydjieva et al 2005</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>].</p><p>Skeletal deformities, especially of the feet and hands (pes cavus, pes equinovarus, flexion contractures in the interphalangeal joints), develop in the course of the disease as a result of the peripheral neuropathy and are present in all affected adults. As muscle weakness progresses, spine deformities (e.g., scoliosis, kyphosis) may also develop and lead to reduction in respiratory capacity [<a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>].</p><p>Sensory abnormalities (numbness) in the lower limbs develop in persons older than age ten years.</p><p>Nerve conduction velocity is normal in infancy at the onset of myelination and subsequently (age >18 months) begins to decline, stabilizing at approximately 20 m/s at around age four to ten years [<a class="bibr" href="#ccfdn.REF.kalaydjieva.2005.65" rid="ccfdn.REF.kalaydjieva.2005.65">Kalaydjieva et al 2005</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. Distal motor latencies are increased.</p><p>Sensory nerve action potentials are of normal amplitude, suggesting a relatively uniform degree of slowing of nerve conduction across nerve fibers, consistent with congenital hypomyelination. As disease progresses, reduction in amplitudes is seen in sensory and motor nerves; some (e.g., in sural nerve) can become unobtainable after age ten years, indicating secondary axonal loss [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>].</p><p>In distal muscles of the upper and lower extremities, neurogenic changes compatible with the underlying neuropathy are seen in all tested individuals [<a class="bibr" href="#ccfdn.REF.tournev.1999b.165" rid="ccfdn.REF.tournev.1999b.165">Tournev et al 1999b</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. Electromyography, performed in six individuals with proximal weakness during the rhabdomyolysis weakness episodes, showed myogenic changes in proximal muscles that were not found after recovery [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>].</p><p>Neuropathologic studies of sural nerve biopsies provide evidence of primary hypomyelination in the absence of morphologic abnormalities in the Schwann cell or axon [<a class="bibr" href="#ccfdn.REF.tournev.1999b.165" rid="ccfdn.REF.tournev.1999b.165">Tournev et al 1999b</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>].</p></div><div id="ccfdn.Central_Nervous_System_Manifestati"><h4>Central Nervous System Manifestations</h4><p><b>Development and cognition.</b> In addition to the delayed motor milestones (attributed partly to the peripheral neuropathy), early intellectual development is slow, with most affected children starting to talk around age three years [<a class="bibr" href="#ccfdn.REF.tournev.1999b.165" rid="ccfdn.REF.tournev.1999b.165">Tournev et al 1999b</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>].</p><p>Formal assessment of cognitive ability reveals variable results, the interpretation of which should take into account visual impairment, poor educational status, and language barriers (i.e., cognitive testing performed in a language other than the individual's primary language). According to available test results, around 10% of affected individuals have normal or borderline cognitive performance, and the rest have mild nonprogressive intellectual deficit. Verbal memory, executive functions, and language skills are similarly affected [<a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>].</p><p><b>Cerebellar involvement</b> of variable severity with ataxia, nystagmus, intention tremor, and dysmetria is common [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>, <a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>, <a class="bibr" href="#ccfdn.REF.lassuthova.2014.46" rid="ccfdn.REF.lassuthova.2014.46">Lassuthova et al 2014</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>]. Ataxia scores remain stable or improve slightly during the course of the disease [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>].</p><p>
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<b>Other neurologic manifestations</b>
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</p><ul><li class="half_rhythm"><div>Pyramidal signs without spasticity and extrapyramidal hyperkinesis are observed in some affected individuals [<a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.chamova.2012" rid="ccfdn.REF.chamova.2012">Chamova 2012</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>].</div></li><li class="half_rhythm"><div>Individuals with <i>CTDP1</i>-CCFDN are at increased risk of developing severe and potentially life-threatening complications related to anesthesia, such as pulmonary edema, inspiratory stridor, malignant hyperthermia, and epileptic seizures [<a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>, <a class="bibr" href="#ccfdn.REF.masters.2017.178" rid="ccfdn.REF.masters.2017.178">Masters et al 2017</a>].</div></li></ul><p><b>Magnetic resonance imaging</b> (MRI) findings of the brain and spinal cord vary among affected individuals and with age. Reported findings include the following:</p><ul><li class="half_rhythm"><div>Cerebral, cerebellar, and cervical spine hypotrophy in childhood; cerebral atrophy with enlargement of the lateral ventricles; and occasionally thin corpus callosum and cerebellar atrophy [<a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>]</div></li><li class="half_rhythm"><div>Diffusion tensor MRI results suggestive of axonal loss in the vermis and medulla oblongata [<a class="bibr" href="#ccfdn.REF.kalaydjieva.2005.65" rid="ccfdn.REF.kalaydjieva.2005.65">Kalaydjieva et al 2005</a>]</div></li><li class="half_rhythm"><div>Myelin immaturity [<a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>]</div></li><li class="half_rhythm"><div>Multifocal white matter hyperintensity on T<sub>2</sub>-weighted imaging; hyperintense lesions in the frontal and parietooccipital periventricular white matter and brain stem (varying from small single to multiple diffuse) [<a class="bibr" href="#ccfdn.REF.cordelli.2010.343" rid="ccfdn.REF.cordelli.2010.343">Cordelli et al 2010</a>, <a class="bibr" href="#ccfdn.REF.chamova.2012" rid="ccfdn.REF.chamova.2012">Chamova 2012</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>, <a class="bibr" href="#ccfdn.REF.chamova.2015.639539" rid="ccfdn.REF.chamova.2015.639539">Chamova et al 2015</a>]</div></li></ul></div><div id="ccfdn.Other"><h4>Other</h4><p><b>Growth.</b> Intrauterine growth restriction is suggested by a study of 22 infants with <i>CTDP1</i>-CCFDN, born at term with significantly lower weight and length than in the general population [<a class="bibr" href="#ccfdn.REF.chamova.2012" rid="ccfdn.REF.chamova.2012">Chamova 2012</a>]:</p><ul><li class="half_rhythm"><div><b>Males.</b> Birth weight 3.22 ± 0.48 kg (reference value 3.9 ± 0.5 kg); length 47.88 ± 3.91 cm (reference 53.1 ± 2.1 cm)</div></li><li class="half_rhythm"><div><b>Females.</b> Birth weight 3.06 ± 0.53 kg (reference 3.8 ± 0.6 kg); length 46.75 ± 4.19 cm (reference 52.5 ± 2.1 cm)</div></li></ul><p>Affected aduIts are of small stature and most are also of subnormal weight [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>]:</p><ul><li class="half_rhythm"><div><b>Adult males.</b> 149.2 ± 5 cm and 47 ± 7.2 kg (reference values: 173 ± 6.8 cm and 73.9 ± 10.4 kg)</div></li><li class="half_rhythm"><div><b>Adult females.</b> 142.4 ± 8.2 cm and 45.8±7.6 kg (reference values: 160.3 ± 6.4 cm and 63 ± 10.7 kg)</div></li></ul><p><b>Endocrine system.</b> Growth hormone levels in <i>CTDP1</i>-CCFDN are in the low-normal range with a pronounced rise after insulin-induced hypoglycemia, suggesting mild regulatory deficiency [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>].</p><p>Sexual development appears unimpaired, with normal secondary characteristics after puberty and normal menarche. However, most adult females report irregular menstrual cycles and early secondary amenorrhea at ages 25-35 years.</p><p>More than half of affected adults of both sexes show evidence of hypogonadotropic hypogonadism, with low testosterone and subnormal follicle stimulating hormone levels in males and low estradiol and subnormal luteinizing hormone levels in females [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. The impact of hypogonadotropic hypogonadism on fertility in individuals with <i>CTDP1</i>-CCFDN has not been assessed.</p><p><b>Bone mineral density</b> is decreased, possibly as a result of both hypogonadotropic hypogonadism and low physical activity as a result of the peripheral neuropathy [<a class="bibr" href="#ccfdn.REF.tournev.1999a.742" rid="ccfdn.REF.tournev.1999a.742">Tournev et al 1999a</a>, <a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>].</p><p><b>Parainfectious rhabdomyolysis,</b> a potentially life-threatening complication that leads to acute kidney failure, may in fact be an integral part of the phenotype. Rhabdomyolysis refers to disintegration of striated muscles and the release of intracellular content into the extracellular compartment, presenting clinically as profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase. Rhabdomyolysis in <i>CTDP1</i>-CCFDN usually develops after febrile illness (mostly viral infections) and is characterized by acute severe proximal weakness and myalgia [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. Proximal muscle weakness is not otherwise typical for <i>CTDP1</i>-CCFDN [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. The episodes are usually recurrent, acute, and dramatic, but resolve spontaneously without progressing to acute renal failure [<a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>, <a class="bibr" href="#ccfdn.REF.mastroyianni.2007.747" rid="ccfdn.REF.mastroyianni.2007.747">Mastroyianni et al 2007</a>, <a class="bibr" href="#ccfdn.REF.lassuthova.2014.46" rid="ccfdn.REF.lassuthova.2014.46">Lassuthova et al 2014</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. Oral corticosteroid treatment for two to three weeks can result in a full recovery within two to six months [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. However, recovery of muscle function may take up to one year. The long-term outcome depends on the recurrence of rhabdomyolysis episodes, and such episodes can lead to deterioration in the clinical course of the peripheral neuropathy [<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>].</p><p>Muscle biopsies have shown mild myopathic features with scattered necrotic fibers, normal histochemical reactions for myophosphorylase and phosphofructokinase, and no evidence of mitochondrial pathology [<a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>].</p></div></div><div id="ccfdn.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>The <i>CTDP1</i>-CCFDN phenotype is consistent, with little variation observed among affected individuals, all of whom are homozygous for the <i>CTDP1</i> Romani founder variant <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a>.</p></div><div id="ccfdn.Nomenclature"><h3>Nomenclature</h3><p>Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) was also referred to as Marinesco-Sjögren syndrome with rhabdomyolysis [<a class="bibr" href="#ccfdn.REF.m_llerfelber.1998.97" rid="ccfdn.REF.m_llerfelber.1998.97">Müller-Felber et al 1998</a>] until it was demonstrated that the individuals described in that study had CCFDN [<a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>].</p><p>The title of this <i>GeneReview</i>, <i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN), is based on the naming approach proposed by <a class="bibr" href="#ccfdn.REF.biesecker.2021.8" rid="ccfdn.REF.biesecker.2021.8">Biesecker et al [2021]</a>, in which mendelian disorders are designated by combining the mutated gene and resulting phenotype.</p></div><div id="ccfdn.Prevalence"><h3>Prevalence</h3><p>The prevalence of <i>CTDP1</i>-CCFDN is unknown. The total number of affected individuals diagnosed to date is approximately 190, all of Romani ancestry. The carrier rate for <i>CTDP1</i> variant <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> is approximately 7% among the Rudari Romani and approximately 1.4% in the general Romani population [<a class="bibr" href="#ccfdn.REF.morar.2004.596" rid="ccfdn.REF.morar.2004.596">Morar et al 2004</a>].</p><p>No affected individuals or carriers in other ethnic groups have been identified to date.</p></div></div><div id="ccfdn.Genetically_Related_Allelic_Disord"><h2 id="_ccfdn_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CTDP1</i>.</p></div><div id="ccfdn.Differential_Diagnosis"><h2 id="_ccfdn_Differential_Diagnosis_">Differential Diagnosis</h2><p>In early infancy, when bilateral congenital cataracts are the only manifestation, the diagnosis of <i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) is made highly probable by the detection of accompanying ophthalmologic abnormalities, such as microcornea and microphthalmia.</p><p>The differential diagnosis with other conditions presenting in the first year of life with congenital cataracts, microcornea, and microphthalmia is narrowed by the delayed developmental milestones in children with <i>CTDP1</i>-CCFDN and subsequent signs of peripheral neuropathy. <i>CTDP1</i>-CCFDN also shares findings with Marinesco-Sjögren syndrome and <i>GBA2</i>-related Marinesco-Sjögren syndrome-like disorder. See <a href="/books/NBK25565/table/ccfdn.T.disorders_of_interest_in_the_dif/?report=objectonly" target="object" rid-ob="figobccfdnTdisordersofinterestinthedif">Table 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTdisordersofinterestinthedif"><a href="/books/NBK25565/table/ccfdn.T.disorders_of_interest_in_the_dif/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobccfdnTdisordersofinterestinthedif"><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="ccfdn.T.disorders_of_interest_in_the_dif"><a href="/books/NBK25565/table/ccfdn.T.disorders_of_interest_in_the_dif/?report=objectonly" target="object" rid-ob="figobccfdnTdisordersofinterestinthedif">Table 3. </a></h4><p class="float-caption no_bottom_margin">Disorders of Interest in the Differential Diagnosis of <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy </p></div></div><p>See also OMIM Phenotypic Series: <a href="https://omim.org/phenotypicSeries/PS309800" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Syndromic Microphthalmia</a> and <a href="https://omim.org/phenotypicSeries/PS116200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cataract</a>.</p></div><div id="ccfdn.Management"><h2 id="_ccfdn_Management_">Management</h2><p>No clinical practice guidelines for <i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) have been published.</p><div id="ccfdn.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>CTDP1</i>-CCFDN and to address the most disabling manifestations, the evaluations summarized in <a href="/books/NBK25565/table/ccfdn.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobccfdnTrecommendedevaluationsfollowin">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTrecommendedevaluationsfollowin"><a href="/books/NBK25565/table/ccfdn.T.recommended_evaluations_followin/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobccfdnTrecommendedevaluationsfollowin"><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="ccfdn.T.recommended_evaluations_followin"><a href="/books/NBK25565/table/ccfdn.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobccfdnTrecommendedevaluationsfollowin">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy </p></div></div></div><div id="ccfdn.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTtreatmentofmanifestationsini"><a href="/books/NBK25565/table/ccfdn.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobccfdnTtreatmentofmanifestationsini"><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="ccfdn.T.treatment_of_manifestations_in_i"><a href="/books/NBK25565/table/ccfdn.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" rid-ob="figobccfdnTtreatmentofmanifestationsini">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy </p></div></div><div id="ccfdn.Developmental_Delay__Intellectual"><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 US; 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, and speech 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, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="ccfdn.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></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>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><div id="ccfdn.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the following evaluations are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTrecommendedsurveillanceforind"><a href="/books/NBK25565/table/ccfdn.T.recommended_surveillance_for_ind/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobccfdnTrecommendedsurveillanceforind"><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="ccfdn.T.recommended_surveillance_for_ind"><a href="/books/NBK25565/table/ccfdn.T.recommended_surveillance_for_ind/?report=objectonly" target="object" rid-ob="figobccfdnTrecommendedsurveillanceforind">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy </p></div></div></div><div id="ccfdn.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>General anesthesia in individuals with <i>CTDP1</i>-CCFDN may cause complications such as pulmonary edema, inspiratory stridor, malignant hyperthermia, and epileptic seizures [<a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al 2004</a>]. Although such complications have not been unequivocally documented, <a class="bibr" href="#ccfdn.REF.masters.2017.178" rid="ccfdn.REF.masters.2017.178">Masters et al [2017]</a> and <a class="bibr" href="#ccfdn.REF.hudec.2022.4207" rid="ccfdn.REF.hudec.2022.4207">Hudec et al [2022]</a> recommend cautious use of general anesthesia until more information on related risks is available.</p><p>Prolonged exercise was reported to provoke myalgia in one individual with <i>CTDP1</i>-CCFDN [<a class="bibr" href="#ccfdn.REF.merlini.2002.231" rid="ccfdn.REF.merlini.2002.231">Merlini et al 2002</a>].</p></div><div id="ccfdn.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger sibs of an affected individual in order to identify as early as possible those who would benefit from early initiation of treatment of ophthalmologic, neurologic, and endocrine manifestations.</p><p>See <a href="#ccfdn.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="ccfdn.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Experience is very limited, as only three females with <i>CTDP1</i>-CCFDN are known to have given birth [<a class="bibr" href="#ccfdn.REF.tournev.2001.210" rid="ccfdn.REF.tournev.2001.210">Tournev et al 2001</a>, <a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al 2014</a>]. The pregnancies were reported as uneventful and were carried to term.</p></div><div id="ccfdn.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="ccfdn.Genetic_Counseling"><h2 id="_ccfdn_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="ccfdn.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) is inherited in an autosomal recessive manner.</p></div><div id="ccfdn.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 a <i>CTDP1</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a <i>CTDP1</i> pathogenic variant and to allow reliable recurrence risk assessment.</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>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>CTDP1</i> 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>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> Unless an affected individual's reproductive partner also has <i>CTDP1</i>-CCFDN or is a carrier (which is more likely in closely knit endogamous communities with a high carrier rate; see <b>Family planning</b>), offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>CTDP1</i>.</p><p><b>Other family members.</b> Each sib of the proband’s parents is at a 50% risk of being a carrier of a <i>CTDP1</i> pathogenic variant.</p></div><div id="ccfdn.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>CTDP1</i> pathogenic variants in the family.</p><p>Because of the endogamous nature of Romani communities and the increased frequency of consanguineous marriages, carrier testing should be considered for the extended families of both parents and future reproductive partners of individuals already determined to be carriers.</p></div><div id="ccfdn.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#ccfdn.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>Carrier testing and genetic counseling should be offered to relatives, especially in view of the endogamous nature of many Romani communities. Even though <i>CTDP1</i>-CCFDN is a very rare disorder in the general population, the high carrier rates in specific communities (see <a href="#ccfdn.Prevalence">Prevalence</a>) translate to an increased probability of couples at high risk of having a child with <i>CTDP1</i>-CCFDN.</div></li><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></ul></div><div id="ccfdn.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>CTDP1</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing for <i>CTDP1</i>-CCFDN are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="ccfdn.Resources"><h2 id="_ccfdn_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/congenital-cataracts-facial-dysmorphism-and-neuropathy/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Congenital cataracts, facial dysmorphism, and neuropathy</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Eye Institute</b>
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</div><div>31 Center Drive</div><div>MSC 2510</div><div>Bethesda MD 20892-2510</div><div>
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<a href="https://www.nei.nih.gov/health/cataract/cataract_facts" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cataracts</a>
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</div></li></ul>
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</div><div id="ccfdn.Molecular_Genetics"><h2 id="_ccfdn_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="figccfdnmolgenTA"><a href="/books/NBK25565/table/ccfdn.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobccfdnmolgenTA"><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="ccfdn.molgen.TA"><a href="/books/NBK25565/table/ccfdn.molgen.TA/?report=objectonly" target="object" rid-ob="figobccfdnmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnmolgenTB"><a href="/books/NBK25565/table/ccfdn.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobccfdnmolgenTB"><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="ccfdn.molgen.TB"><a href="/books/NBK25565/table/ccfdn.molgen.TB/?report=objectonly" target="object" rid-ob="figobccfdnmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy (View All in OMIM) </p></div></div><div id="ccfdn.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The carboxy-terminal domain phosphatase 1 (CTDP1), also known as transcription factor IIF-associating CTD phosphatase 1 (FCP1), is a widely expressed nuclear protein with a catalytic N-terminal part, a phospho-protein-binding BRCT domain common to cell cycle checkpoint proteins and involved in protein-protein interactions, and a C-terminal nuclear localization signal [<a class="bibr" href="#ccfdn.REF.archambault.1997.14300" rid="ccfdn.REF.archambault.1997.14300">Archambault et al 1997</a>, <a class="bibr" href="#ccfdn.REF.cho.1999.1540" rid="ccfdn.REF.cho.1999.1540">Cho et al 1999</a>, <a class="bibr" href="#ccfdn.REF.kobor.1999.55" rid="ccfdn.REF.kobor.1999.55">Kobor et al 1999</a>]. CTDP1 is involved in the regulation of eukaryotic transcription, its main function being the regulation of the phosphorylation level of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII). The CTD serves as the platform for the recruitment, assembly, and interaction of multimeric protein complexes involved in the different stages of transcription and in the post-transcriptional modifications of the nascent mRNA [<a class="bibr" href="#ccfdn.REF.maniatis.2002.499" rid="ccfdn.REF.maniatis.2002.499">Maniatis & Reed 2002</a>]. The coupling and coordination of these processes is controlled by the changing level and pattern of phosphorylation of the serine 2 and 5 residues in the CTD, a "CTD code" that specifies the position of RNAPII in a transcription cycle [<a class="bibr" href="#ccfdn.REF.maniatis.2002.499" rid="ccfdn.REF.maniatis.2002.499">Maniatis & Reed 2002</a>]. In vitro experiments have implicated CTDP1 in virtually all stages of the transcription cycle and multiple other processes regulating gene expression, in addition to the RNAPII recycling during transcription, such as mobilization of stored RNAPII sequestered in depots in the phosphorylated form [<a class="bibr" href="#ccfdn.REF.palancade.2001.6359" rid="ccfdn.REF.palancade.2001.6359">Palancade et al 2001</a>], the recruitment of the splicing machinery [<a class="bibr" href="#ccfdn.REF.licciardo.2003.999" rid="ccfdn.REF.licciardo.2003.999">Licciardo et al 2003</a>], and chromatin remodeling through histone methylation [<a class="bibr" href="#ccfdn.REF.amente.2005.683" rid="ccfdn.REF.amente.2005.683">Amente et al 2005</a>].</p><p><b>Mechanism of disease causation.</b>
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<i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy (<i>CTDP1</i>-CCFDN) is caused by reduced level/function of CTDP1. Some normal splicing (15%-35%) occurs in CCFDN cells; therefore, <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> results in a partial deficiency of CTDP1 [<a class="bibr" href="#ccfdn.REF.varon.2003.185" rid="ccfdn.REF.varon.2003.185">Varon et al 2003</a>, <a class="bibr" href="#ccfdn.REF.kalaydjieva.2016" rid="ccfdn.REF.kalaydjieva.2016">Kalaydjieva et al 2016</a>].</p><p><b><i>CTDP1</i>-specific laboratory technical considerations.</b> Alternative splicing generates two isoforms: isoform a (12 exons) is a 3,775-nucleotide transcript; isoform b (11 exons) is 3,612 nucleotides.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figccfdnTnotablectdp1pathogenicvariant"><a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobccfdnTnotablectdp1pathogenicvariant"><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="ccfdn.T.notable_ctdp1_pathogenic_variant"><a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">Table 7. </a></h4><p class="float-caption no_bottom_margin">Notable <i>CTDP1</i> Pathogenic Variants </p></div></div></div></div><div id="ccfdn.Chapter_Notes"><h2 id="_ccfdn_Chapter_Notes_">Chapter Notes</h2><div id="ccfdn.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>13 October 2022 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 April 2017 (ha/bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>2 October 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>16 August 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>2 March 2010 (me) Review posted live</div></li><li class="half_rhythm"><div>29 October 2009 (lk) Original submission</div></li></ul></div></div><div id="ccfdn.References"><h2 id="_ccfdn_References_">References</h2><div id="ccfdn.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.amente.2005.683">Amente S, Naplitano G, Licciardo P, Monti M, Pucci P, Lania L, Majello B. Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation. <span><span class="ref-journal">FEBS Lett. </span>2005;<span class="ref-vol">579</span>:683–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15670829" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15670829</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.archambault.1997.14300">Archambault J, Chambers RD, Kobor MS, Ho Y, Cartier M, Bolotin D, Andrews B, Kane CM, Greenblatt J. An essential component of a C-terminal domain phosphatase that interacts with transcription factor IIF in S. cerevisiae. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>1997;<span class="ref-vol">94</span>:14300–5.</span> [<a href="/pmc/articles/PMC24951/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC24951</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9405607" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9405607</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.biesecker.2021.8">Biesecker LG, Adam MP, Alkuraya FS, Amemiya AR, Bamshad MJ, Beck AE, Bennett JT, Bird LM, Carey JC, Chung B, Clark RD, Cox TC, Curry C, Dinulos MBP, Dobyns WB, Giampietro PF, Girisha KM, Glass IA, Graham JM Jr, Gripp KW, Haldeman-Englert CR, Hall BD, Innes AM, Kalish JM, Keppler-Noreuil KM, Kosaki K, Kozel BA, Mirzaa GM, Mulvihill JJ, Nowaczyk MJM, Pagon RA, Retterer K, Rope AF, Sanchez-Lara PA, Seaver LH, Shieh JT, Slavotinek AM, Sobering AK, Stevens CA, Stevenson DA, Tan TY, Tan WH, Tsai AC, Weaver DD, Williams MS, Zackai E, Zarate YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics. <span><span class="ref-journal">Am J Hum Genet. </span>2021;<span class="ref-vol">108</span>:8–15.</span> [<a href="/pmc/articles/PMC7820621/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7820621</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33417889" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33417889</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.chamova.2012">Chamova T. <em>Investigation of the Cognitive Impairment of Patients with Neuromuscular Disorders.</em> Sofia, Bulgaria: Sofia Medical University; 2012.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.chamova.2015.639539">Chamova T, Zlatareva D, Raycheva M, Bichev S, Kalaydjieva L, Tournev I. Cognitive impairment and brain imaging characteristics of patients with congenital cataracts, facial dysmorphism, neuropathy syndrome. <span><span class="ref-journal">Behav Neurol. </span>2015;<span class="ref-vol">2015</span>:639539. </span> [<a href="/pmc/articles/PMC4427823/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4427823</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26060356" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26060356</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.cho.1999.1540">Cho H, Kim TK, Mancebo H, Lane WS, Flores O, Reinberg D. A protein phosphatase functions to recycle RNA polymerase II. <span><span class="ref-journal">Genes & Dev. </span>1999;<span class="ref-vol">13</span>:1540–52.</span> [<a href="/pmc/articles/PMC316795/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC316795</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10385623" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10385623</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.cordelli.2010.343">Cordelli DM, Garone C, Marchiani V, Lodi R, Tonon C, Ferrari S, Seri M, Franzoni E. Progressive cerebral white matter involvement in a patient with congenital cataracts facial dysmorphisms neuropathy (CCFDN). <span><span class="ref-journal">Neuromuscul Disord. </span>2010;<span class="ref-vol">20</span>:343–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20350809" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20350809</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.haugarvoll.2017.e0169309">Haugarvoll K, Johansson S, Rodriguez CE, Boman H, Haukanes BI, Bruland O, Roque F, Jonassen I, Blomqvist M, Telstad W, Månsson JE, Knappskog PM, Bindoff LA. GBA2 mutations cause a Marinesco-Sjögren-like syndrome: genetic and biochemical studies. <span><span class="ref-journal">PLoS One. </span>2017;<span class="ref-vol">12</span>:e0169309. </span> [<a href="/pmc/articles/PMC5215700/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5215700</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28052128" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28052128</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.hudec.2022.4207">Hudec J, Kosinova M, Prokopova T, Filipovic M, Repko M, Stourac P. Anesthesia of a patient with congenital cataract, facial dysmorphism, and neuropathy syndrome for posterior scoliosis: a case report. <span><span class="ref-journal">World J Clin Cases. </span>2022;<span class="ref-vol">10</span>:4207–13.</span> [<a href="/pmc/articles/PMC9131212/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9131212</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35665120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35665120</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.kalaydjieva.2016">Kalaydjieva L, Chamova T, Gooding R. Carboxy-terminal domain phosphatase 1: congenital cataracts-facial dysmorphism-neuropathy syndrome. In: Erickson RP, Wynshaw-Boris AJ, eds. <em>Epstein's Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis.</em> 3 ed. Oxford: Oxford University Press; 2016:1001-5.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.kalaydjieva.2005.65">Kalaydjieva L, Lochmüller H, Tournev I, Baas F, Beres J, Colomer J, Guergueltcheva V, Herrmann R, Karcagi V, King R, Miyata T, Müllner-Eidenböck A, Okuda T, Milic Rasic V, Santos M, Talim B, Vilchez J, Walter M, Urtizberea A, Merlini L. 125th ENMC International Workshop: neuromuscular disorders in the Roma (Gypsy) population, 23-25 April 2004, Naarden, the Netherlands. <span><span class="ref-journal">Neuromuscul Disord. </span>2005;<span class="ref-vol">15</span>:65–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15639123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15639123</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.kobor.1999.55">Kobor MS, Archambault J, Lester W, Holstege FC, Gieladi O, Jausma DB, Jennings EG, Kouyoumdjan F, Davidson AR, Young RA, Greenblatt J. An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae. <span><span class="ref-journal">Mol Cell. </span>1999;<span class="ref-vol">4</span>:55–62.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10445027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10445027</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.lassuthova.2014.46">Lassuthova P, Sišková D, Haberlová J, Sakmaryová I, Filouš A, Seeman P. Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) in 10 Czech Gypsy children--frequent and underestimated cause of disability among Czech Gypsies. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2014;<span class="ref-vol">9</span>:46.</span> [<a href="/pmc/articles/PMC3976362/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3976362</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24690360" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24690360</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.licciardo.2003.999">Licciardo P, Amente S, Ruggiero L, Monti M, Pucci P, Lania L, Majello B. The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP. <span><span class="ref-journal">Nucl Acids Res. </span>2003;<span class="ref-vol">31</span>:999–1005.</span> [<a href="/pmc/articles/PMC149217/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC149217</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12560496" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12560496</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.maniatis.2002.499">Maniatis T, Reed R. An extensive network of coupling among gene expression machines. <span><span class="ref-journal">Nature. </span>2002;<span class="ref-vol">416</span>:499–506.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11932736" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11932736</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.masters.2017.178">Masters OW, Bergmans E, Thies KC. Anaesthesia and orphan disease: a child with Congenital Cataract Facial Dysmorphism neuropathy (CCFDN) syndrome: a case report. <span><span class="ref-journal">Eur J Anaesthesiol. </span>2017;<span class="ref-vol">34</span>:178–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28141735" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28141735</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.mastroyianni.2007.747">Mastroyianni SD, Garoufi A, Voudris K, Skardoutsou A, Gooding R, Kalaydjieva L. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis. <span><span class="ref-journal">Eur J Pediatr. </span>2007;<span class="ref-vol">166</span>:747–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17195938" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17195938</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.merlini.2002.231">Merlini L, Gooding R, Lochmueller H, Walter MC, Angelicheva D, Talim B, Hallmayer J, Kalaydjieva L. Genetic identity of Marinesco-Sjögren/ myoglobinuria and CCFDN syndromes. <span><span class="ref-journal">Neurology. </span>2002;<span class="ref-vol">58</span>:231–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11805249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11805249</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.morar.2004.596">Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V, Schmidt C, Abicht A, Lochmüller H, Tordai A, Kalmar L, Nagy M, Karcagi V, Jeanpierre M, Herczegfalvi A, de Pablo R, Kucinskas V, Kalaydjieva L. Mutation history of the Roma/Gypsies. <span><span class="ref-journal">Am J Hum Genet. </span>2004;<span class="ref-vol">75</span>:596–609.</span> [<a href="/pmc/articles/PMC1182047/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1182047</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15322984" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15322984</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.m_llerfelber.1998.97">Müller-Felber W, Zafiriou D, Scheck R, Pätzke I, Toepfer M, Pongratz DE, Walther U. Marinesco-Sjögren syndrome with rhabdomyolysis. A new subtype of the disease. <span><span class="ref-journal">Neuropediatrics. </span>1998;<span class="ref-vol">29</span>:97–101.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9638664" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9638664</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck A, Moser E, Klebermass N, Amon M, Mernert G, Walther M, Lochmueller H, Kalaydjieva L. Ocular features of the CCFDN syndrome (congenital cataracts facial dysmorphism neuropathy). <span><span class="ref-journal">Ophthalmology. </span>2004;<span class="ref-vol">111</span>:1415–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15234148" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15234148</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.palancade.2001.6359">Palancade B, Dubois MF, Dahmus ME, Bensaude O. Transcription-independent RNA polymerase II dephosphorylation by the FCP1 carboxy-terminal domain phosphatase in Xenopus laevis early embryos. <span><span class="ref-journal">Mol Cell Biol. </span>2001;<span class="ref-vol">21</span>:6359–68.</span> [<a href="/pmc/articles/PMC99784/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC99784</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11533226" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11533226</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.tournev.1999a.742">Tournev I, Kalaydjieva L, Youl B, Ishpekova B, Guerguelcheva V, Kamenov O, Katzarova M, Kamenov Z, Raicheva-Ternzieva M, King RHM, Petkov R, Shmarov A, Dimitrova G, Popova N, Uzunova M, Milanov S, Petrova J, Petkov Y, Kolarov G, Anev L, Radeva O, Thomas PK. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations. <span><span class="ref-journal">Ann Neurol. </span>1999a;<span class="ref-vol">45</span>:742–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10360766" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10360766</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.tournev.1999b.165">Tournev I, King RH, Workman J, Nourallah M, Muddle JR, Kalaydjieva L, Romanski K, Thomas PK. Peripheral nerve abnormalities in the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome. <span><span class="ref-journal">Acta Neuropathol. </span>1999b;<span class="ref-vol">98</span>:165–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10442556" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10442556</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.tournev.2001.210">Tournev I, Thomas P, Gooding R, Angelicheva D, King R, Youl B, Guerueltcheva V, Ishpekova B, Blechsmidt K, Swoboda K, Petkov R, Molnar M, Kamenov Z, Siska E, Taneva N, Borisova P, Lupu C, Raycheva M, Trifonova N, Popova A, Corches A, Litvinenko I, Merlini L, Katzarova M, Tzankov B, Popa G, Akkari A, Rosenthal A, Donzelli O, Kalaydjieva L. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome – clinical, neuropathological and genetic investigation. <span><span class="ref-journal">Acta Myologica. </span>2001;<span class="ref-vol">20</span>:210–9.</span></div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.varon.2003.185">Varon R, Gooding R, Steglich C, Marns L, Tang H, Angelicheva D, Yong KK, Ambrugger P, Reinhold A, Morar B, Baas F, Kwa M, Tournev I, Guerguelcheva V, Kremensky I, Lochmüller H, Müllner-Eidenböck A, Merlini L, Neumann L, Bürger J, Walter M, Swoboda K, Thomas PK, von Moers A, Risch N, Kalaydjieva L. Partial deficiency of the C-terminal domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. <span><span class="ref-journal">Nat Genet. </span>2003;<span class="ref-vol">35</span>:185–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14517542" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14517542</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ccfdn.REF.walter.2014.1337">Walter MC, Bernert G, Zimmermann U, Müllner-Eidenböck A, Moser E, Kalaydjieva L, Lochmüller H, Müller-Felber W. Long-term follow-up in patients with CCFDN syndrome. <span><span class="ref-journal">Neurology. </span>2014;<span class="ref-vol">83</span>:1337–44.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25186864" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25186864</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK25565_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Luba Kalaydjieva</span>, MD, PhD<div class="affiliation small">Laboratory for Molecular Genetics<br />Harry Perkins Institute of Medical Research and Centre for Medical Research<br />The University of Western Australia<br />Perth, Australia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ua.ude.awu@aveijdyalak.abul" class="oemail">ua.ude.awu@aveijdyalak.abul</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Teodora Chamova</span>, MD, PhD<div class="affiliation small">Department of Neurology<br />University Hospital Alexandrovska<br />Medical University of Sofia<br />Sofia, Bulgaria<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gb.vba@hctarodoet" class="oemail">gb.vba@hctarodoet</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">March 2, 2010</span>; Last Update: <span itemprop="dateModified">October 13, 2022</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Kalaydjieva L, Chamova T. CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy. 2010 Mar 2 [Updated 2022 Oct 13]. 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/csnk2b-ndd/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/ctnnb1-ndd/?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="figobccfdnTmoleculargenetictestingusedi"><div id="ccfdn.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.molecular_genetic_testing_used_i_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_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CTDP1</i>
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</td><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> <sup>3</sup></td><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>3, 4</sup></td></tr><tr><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>5</sup></td><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 6.</td></tr><tr><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>7</sup></td><td headers="hd_h_ccfdn.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>4</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="ccfdn.TF.1.1"><p class="no_margin">See <a href="/books/NBK25565/?report=reader#ccfdn.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="ccfdn.TF.1.2"><p class="no_margin">See <a href="#ccfdn.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="ccfdn.TF.1.3"><p class="no_margin">Romani founder variant <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a> is the only pathogenic variant reported to date.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="ccfdn.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#ccfdn.REF.stenson.2020.1197" rid="ccfdn.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="ccfdn.TF.1.5"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="ccfdn.TF.1.6"><p class="no_margin">Sequence analysis should include detection of deep intronic variants including <a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobccfdnTnotablectdp1pathogenicvariant">c.863+389C>T</a>, the only pathogenic variant reported to date.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="ccfdn.TF.1.7"><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.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnTctdp1relatedcongenitalcataract"><div id="ccfdn.T.ctdp1related_congenital_cataract" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.ctdp1related_congenital_cataract/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.ctdp1related_congenital_cataract_lrgtbl__"><table><thead><tr><th id="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_ccfdn.T.ctdp1related_congenital_cataract_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_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ocular manifestations</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital cataracts, microcornea, microphthalmia, micropupils</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysmorphic facial features</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prominent midface w/well-developed nose, thickening of perioral tissues, forwardly directed anterior dentition, & micrognathia; more pronounced in affected males & in adulthood</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypomyelinating peripheral neuropathy</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Symmetric & distally accentuated, w/predominantly motor involvement progressing to severe disability by 3rd decade of life</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay /<br />Intellectual disability</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~80%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Delayed motor milestones (attributed partly to peripheral neuropathy), delayed early intellectual development, w/most affected children starting to talk at age ~3 yrs</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebellar manifestations</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~20%-40%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxias of stance, gait, nystagmus, intention tremor, & dysmetria</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain & spinal cord MRI abnormalities</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>90%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebral atrophy, thin corpus callosum, enlargement of lateral ventricles, & focal lesions in subcortical white matter (different in number & size), consistent w/demyelination</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth deficiency</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>90%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intrauterine growth restriction w/low weight & length at birth</td></tr><tr><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrine manifestations</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_ccfdn.T.ctdp1related_congenital_cataract_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low levels of growth hormone & hypogonadotropic hypogonadism</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobccfdnTdisordersofinterestinthedif"><div id="ccfdn.T.disorders_of_interest_in_the_dif" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Disorders of Interest in the Differential Diagnosis of <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.disorders_of_interest_in_the_dif/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.disorders_of_interest_in_the_dif_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Differential Disorder</th><th id="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Characteristics</th><th id="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment(s)</th></tr></thead><tbody><tr><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GALK1</i>
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</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Galactokinase (GALK) deficiency (OMIM <a href="https://omim.org/entry/230200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">230200</a>)</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cataracts, ↑ plasma concentration of galactose, & ↑ urinary excretion of galactitol</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GALK deficiency is the main differential diagnosis of <i>CTDP1</i>-CCFDN in infants of Romani ancestry. In Romani persons, GALK deficiency is caused by <i>GALK1</i> founder variant c.82C>A. <sup>1</sup></td></tr><tr><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GBA2</i>
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</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>GBA2</i>-related Marinesco-Sjögren syndrome-like disorder <sup>2</sup></td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive cerebellar ataxia in early childhood accompanied by lower-limb spasticity & axonal peripheral neuropathy → weakness, muscle wasting, & foot deformities. Normal early psychomotor development; mild progressive cognitive decline accompanies other progressive CNS findings. Bilateral cataracts are observed later in disease course. <sup>2</sup></td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/homozygous <i>GBA2</i> variant c.1528_1529del (p.Met510ValfsTer17) <sup>2</sup></td></tr><tr><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>INTS1</i>
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</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>INTS1</i>-related NDD (OMIM <a href="https://omim.org/entry/618571" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618571</a>)</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NDD w/cataracts, poor growth, & dysmorphic facies</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>INTS1</i>-related NDD is not assoc w/peripheral neuropathy.</td></tr><tr><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SIL1</i>
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</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/mss/?report=reader">Marinesco-Sjögren syndrome</a> (MSS)</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebellar ataxia w/cerebellar atrophy, early-onset (not necessarily congenital) cataracts, myopathy, muscle weakness, & hypotonia. Addl features may incl psychomotor delay, hypergonadotropic hypogonadism, short stature, & skeletal abnormalities. Usually presents w/muscular hypotonia in early infancy. Cataracts can develop rapidly & typically require lens extraction in 1st decade of life.</td><td headers="hd_h_ccfdn.T.disorders_of_interest_in_the_dif_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical investigations providing the best distinction between <i>CTDP1</i>-CCFDN & MSS are ophthalmologic (cataracts in both disorders but extensive involvement of the anterior eye segment in <i>CTDP1</i>-CCFDN); neurophysiologic (↓ nerve conduction velocity in <i>CTDP1</i>-CCFDN); & neuroimaging (cerebellar atrophy in MSS). Electron-microscopic ultrastructural changes on muscle biopsy are thought to be specific to MSS.</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">AR = autosomal recessive; CNS = central nervous system; MOI = mode of inheritance; NDD = neurodevelopmental disorder</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="ccfdn.TF.3.1"><p class="no_margin">See <a href="/books/n/gene/founder_romani/?report=reader">Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Romani Population</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="ccfdn.TF.3.2"><p class="no_margin">
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<a class="bibr" href="#ccfdn.REF.haugarvoll.2017.e0169309" rid="ccfdn.REF.haugarvoll.2017.e0169309">Haugarvoll et al [2017]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnTrecommendedevaluationsfollowin"><div id="ccfdn.T.recommended_evaluations_followin" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.recommended_evaluations_followin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.recommended_evaluations_followin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ccfdn.T.recommended_evaluations_followin_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_ccfdn.T.recommended_evaluations_followin_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_ccfdn.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for cataracts & other ocular manifestations.</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic exam incl measurements of nerve conduction velocity</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for peripheral neuropathy & cerebellar involvement.</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
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<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Mobility, ADL, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul></td></tr><tr><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_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_ccfdn.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<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_ccfdn.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Endocrine</b>
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</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrinology eval</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess growth, fertility issues, & osteopenia.</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
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<br />
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<b>counseling</b>
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</td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_ccfdn.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>CTDP1</i>-CCFDN to facilitate medical & personal decision making</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; <i>CTDP1</i>-CCFDN = <i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="ccfdn.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnTtreatmentofmanifestationsini"><div id="ccfdn.T.treatment_of_manifestations_in_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.treatment_of_manifestations_in_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.treatment_of_manifestations_in_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_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_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical treatment for cataract removal w/close follow up for unusually exaggerated postoperative inflammatory reactions & strong unspecific foreign-body reaction to contact lenses & intraocular lenses</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Surgical removal of cataracts may be complicated by micropupils & fibrotic pupillary margins, requiring alternative mechanical methods of dilation. <sup>1</sup></div></li><li class="half_rhythm"><div>Intraocular lenses are generally better tolerated than contact lenses.</div></li></ul>
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</td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Peripheral neuropathy</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Mgmt per physical medicine & rehab</div></li><li class="half_rhythm"><div>Corrective surgery per orthopedics for secondary bone deformities</div></li></ul>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider need for positioning & mobility devices, disability parking placard.</td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_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>
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<br />
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<b>Intellectual disability</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#ccfdn.Developmental_Delay__Intellectual">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cerebellar manifestations</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt per physical medicine & rehab / PT & OT</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anesthesia complications</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Close postoperative monitoring & possibly intensive postoperative care</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For ↑ risk of severe & potentially life-threatening complications (e.g., pulmonary edema, inspiratory stridor, malignant hyperthermia, epileptic seizures) <sup>2</sup></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth deficiency</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No known treatment; growth hormone levels in <i>CTDP1</i>-CCFDN are in low-normal range & growth hormone treatment is not expected to have considerable effect.</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Osteoporosis</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Regular rehab</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypogonadotropic hypogonadism</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hormone replacement therapy may be considered in young females w/secondary amenorrhea due to ↑ risk of osteoporosis.</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Rhabdomyolysis</b>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Urgent assessment w/onset of any signs/symptoms of rhabdomyolysis (e.g., muscle weakness, myoglobinuria)</div></li><li class="half_rhythm"><div>Oral corticosteroid treatment for 2-3 wks can result in full recovery w/in 2-6 mos. <sup>3</sup></div></li></ul>
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</td><td headers="hd_h_ccfdn.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Affected persons & care providers must be aware of risk of rhabdomyolysis, usually following febrile illness (e.g., viral infections).</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"><i>CTDP1</i>-CCFDN = <i>CTDP1</i>-related congenital cataracts, facial dysmorphism, and neuropathy; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="ccfdn.TF.5.1"><p class="no_margin">
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<a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al [2004]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="ccfdn.TF.5.2"><p class="no_margin"><a class="bibr" href="#ccfdn.REF.m_llnereidenb_ck.2004.1415" rid="ccfdn.REF.m_llnereidenb_ck.2004.1415">Müllner-Eidenböck et al [2004]</a>, <a class="bibr" href="#ccfdn.REF.hudec.2022.4207" rid="ccfdn.REF.hudec.2022.4207">Hudec et al [2022]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="ccfdn.TF.5.3"><p class="no_margin">
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<a class="bibr" href="#ccfdn.REF.walter.2014.1337" rid="ccfdn.REF.walter.2014.1337">Walter et al [2014]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnTrecommendedsurveillanceforind"><div id="ccfdn.T.recommended_surveillance_for_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>CTDP1</i>-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.recommended_surveillance_for_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.recommended_surveillance_for_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ccfdn.T.recommended_surveillance_for_ind_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_ccfdn.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic involvement</b>
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</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology exam</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or per treating ophthalmologist(s)</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic exam</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_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_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit throughout childhood</td></tr><tr><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Endocrine</b>
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</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrine eval to assess growth, fertility issues, & osteopenia</td><td headers="hd_h_ccfdn.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnmolgenTA"><div id="ccfdn.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_ccfdn.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_ccfdn.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_ccfdn.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_ccfdn.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_ccfdn.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_ccfdn.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_ccfdn.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/9150" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CTDP1</i>
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</a>
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</td><td headers="hd_b_ccfdn.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=9150" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">18q23</a>
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</td><td headers="hd_b_ccfdn.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/Q9Y5B0" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RNA polymerase II subunit A C-terminal domain phosphatase</a>
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</td><td headers="hd_b_ccfdn.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/CTDP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CTDP1 - Leiden Muscular Dystrophy pages</a>
|
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</td><td headers="hd_b_ccfdn.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=CTDP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CTDP1</a>
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</td><td headers="hd_b_ccfdn.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=CTDP1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CTDP1</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="ccfdn.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
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chromosome locus from
|
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobccfdnmolgenTB"><div id="ccfdn.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy (<a href="/omim/604168,604927" 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/NBK25565/table/ccfdn.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.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/604168" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604168</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CONGENITAL CATARACTS, FACIAL DYSMORPHISM, AND NEUROPATHY; CCFDN</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604927" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604927</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C-TERMINAL DOMAIN OF RNA POLYMERASE II SUBUNIT A, PHOSPHATASE OF, SUBUNIT 1; CTDP1</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobccfdnTnotablectdp1pathogenicvariant"><div id="ccfdn.T.notable_ctdp1_pathogenic_variant" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>CTDP1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK25565/table/ccfdn.T.notable_ctdp1_pathogenic_variant/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ccfdn.T.notable_ctdp1_pathogenic_variant_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004715.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004715<wbr style="display:inline-block"></wbr>​.5</a>
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</td><td headers="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.863+389C>T <sup>2</sup><br />(IVS6+389C>T)</td><td headers="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_ccfdn.T.notable_ctdp1_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Romani population</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="ccfdn.TF.7.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="ccfdn.TF.7.2"><p class="no_margin">Nucleotide change (c.863+389C>T) triggers an unusual mechanism of aberrant splicing [<a class="bibr" href="#ccfdn.REF.varon.2003.185" rid="ccfdn.REF.varon.2003.185">Varon et al 2003</a>]. It creates a canonic donor splice site, which activates an upstream cryptic acceptor site and triggers a rare mechanism of aberrant splicing. The cryptic acceptor site is utilized together with the regular intron 6 donor site to splice out an upstream part of the intron, while the newly created donor site together with the regular intron 6 acceptor site serve for the splicing of a downstream part of the intron. An intermediate Alu sequence of 95 nucleotides is inserted into the processed <i>CTDP1</i> mRNA, resulting in a premature termination signal 17 codons downstream of exon 6.</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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