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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Chondrodysplasia Punctata 1, X-Linked" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2020/10/15" /><meta name="citation_author" content="Nancy E Braverman" /><meta name="citation_author" content="Michael B Bober" /><meta name="citation_author" content="Nicola Brunetti-Pierri" /><meta name="citation_author" content="Sharon F Suchy" /><meta name="citation_pmid" content="20301713" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1544/" /><meta name="citation_keywords" content="Arylsulfatase E Deficiency" /><meta name="citation_keywords" content="Arylsulfatase E Deficiency" /><meta name="citation_keywords" content="Arylsulfatase L" /><meta name="citation_keywords" content="ARSL" /><meta name="citation_keywords" content="Chondrodysplasia Punctata 1, X-Linked" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Chondrodysplasia Punctata 1, X-Linked" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Nancy E Braverman" /><meta name="DC.Contributor" content="Michael B Bober" /><meta name="DC.Contributor" content="Nicola Brunetti-Pierri" /><meta name="DC.Contributor" content="Sharon F Suchy" /><meta name="DC.Date" content="2020/10/15" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1544/" /><meta name="description" content="X-linked chondrodysplasia punctata 1 (CDPX1) is characterized by chondrodysplasia punctata (stippled epiphyses), brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK1544_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1544_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/cd-chst3/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/x-dcdp/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK1544_"><span class="title" itemprop="name">Chondrodysplasia Punctata 1, X-Linked</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Arylsulfatase E Deficiency</div><p class="contrib-group"><span itemprop="author">Nancy E Braverman</span>, MS, MD, <span itemprop="author">Michael B Bober</span>, MD, PhD, <span itemprop="author">Nicola Brunetti-Pierri</span>, MD, and <span itemprop="author">Sharon F Suchy</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK1544_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1544_ai__"><div class="contrib half_rhythm"><span itemprop="author">Nancy E Braverman</span>, MS, MD<div class="affiliation small">Departments of Pediatrics and Human Genetics
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McGill University and Research Institute of the McGill University Health Center
|
||
Montreal, Quebec, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.lligcm@namrevarb.ycnan" class="oemail">ac.lligcm@namrevarb.ycnan</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Michael B Bober</span>, MD, PhD<div class="affiliation small">Director, Skeletal Dysplasia Program
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AI duPont Hospital for Children
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Wilmington, Delaware<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.sruomen@rebobm" class="oemail">gro.sruomen@rebobm</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Nicola Brunetti-Pierri</span>, MD<div class="affiliation small">Telethon Institute of Genetics and Medicine;
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Department of Translational Medicine
|
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Federico II University of Naples
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Naples, Italy<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ti.megit@ittenurb" class="oemail">ti.megit@ittenurb</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Sharon F Suchy</span>, PhD<div class="affiliation small">Director, Inherited Metabolic Disorders
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GeneDx, Inc
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Gaithersburg, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.xdeneg@yhcuss" class="oemail">moc.xdeneg@yhcuss</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">April 22, 2008</span>; Last Update: <span itemprop="dateModified">October 15, 2020</span>.</p><p><em>Estimated reading time: 18 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cdp1-xlr.Summary" itemprop="description"><h2 id="_cdp1-xlr_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata 1 (CDPX1) is characterized by chondrodysplasia punctata (stippled epiphyses), brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. Although most affected males have minimal morbidity and skeletal findings that improve by adulthood, some have significant medical problems including respiratory involvement, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and intellectual disability.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of CDPX1 is established in a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with typical clinical and radiographic findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. Testing of ARSL enzymatic activity is not currently available on a clinical basis.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment of respiratory difficulty as per ENT and/or pulmonologist including nasal stents and oxygen as needed. Severe maxillary hypoplasia or maxillary retrognathia may require reconstructive surgery in older individuals. Instability of the cervical spine may require a cervical collar or spinal fusion. Decompression for cervical spine stenosis as needed. Hearing aids and pressure equalization tubes may be needed for hearing loss. Therapies and individualized education plan for those with developmental delay and/or learning disorder. Standard treatment for vision issues and cardiac anomalies.</p><p><i>Surveillance:</i> Routine monitoring for growth deficiency, scoliosis, hearing loss, developmental delay, and ocular abnormalities. Assess for cervical spine instability by flexion-extension radiographs every six to twelve months until growth is completed.</p><p><i>Agents/circumstances to avoid:</i> In individuals with cervical spine instability, extreme neck extension and neck flexion and contact sports should be avoided. In case of general anesthesia, the cervical spine should be assessed by imaging prior to the procedure.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>CDPX1 is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner. If the mother of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and thus far have not been affected. Males with CDPX1 pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk relatives and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for at-risk pregnancies are possible if the <i>ARSL</i> pathogenic variant has been identified in the family.</p></div></div><div id="cdp1-xlr.Diagnosis"><h2 id="_cdp1-xlr_Diagnosis_">Diagnosis</h2><div id="cdp1-xlr.Suggestive_Findings"><h3>Suggestive Findings</h3><p><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata 1 (CDPX1) should be <b>suspected</b> in a <b>male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b> with the following clinical and radiographic findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Brachytelephalangy (shortening of the distal phalanges)</div></li><li class="half_rhythm"><div>Nasomaxillary hypoplasia</div><ul><li class="half_rhythm"><div>Hypoplasia of the anterior nasal spine</div></li><li class="half_rhythm"><div>Flattened nasal base</div></li><li class="half_rhythm"><div>Reduced nasal tip protrusion with short columella</div></li><li class="half_rhythm"><div>Crescent-shaped nostrils</div></li><li class="half_rhythm"><div>Vertical grooves within the alae nasi (in some individuals)</div></li></ul></li><li class="half_rhythm"><div>Postnatal short stature</div></li></ul><p>
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<b>Radiographic findings</b>
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</p><ul><li class="half_rhythm"><div>Chondrodysplasia punctata (stippled epiphyses) are observed on skeletal x-rays in infancy, usually of the ankle and distal phalanges, although they can be more generalized to include epiphyses of long bones, vertebrae, hips, costochondral junctions, and hyoid bone. An inverted triangular shape of the distal phalanges with lateral stippling at the apex is characteristic. Stippling is usually symmetric and age dependent and cannot be seen after normal epiphyseal ossification at age two to three years.</div></li><li class="half_rhythm"><div>Calcifications can also occur in the larynx, trachea, and main stem bronchi (structures that do not normally ossify) and cause stenosis.</div></li><li class="half_rhythm"><div>Vertebral abnormalities are common and include dysplastic and hypoplastic vertebrae and coronal or sagittal clefts. Cervical vertebral abnormalities can cause cervical kyphosis, cervical stenosis, and atlantoaxial instability.</div></li></ul><p><b>Laboratory findings.</b> Normal clotting function (PT and PTT) and clotting factors II, VII, IX, and X (See <a href="#cdp1-xlr.Differential_Diagnosis">Differential Diagnosis</a>.)</p></div><div id="cdp1-xlr.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of CDPX1 is <b>established</b> in a <b>male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b> with <a href="#cdp1-xlr.Suggestive_Findings">suggestive findings</a> and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ARSL</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1544/table/cdp1-xlr.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcdp1xlrTmoleculargenetictestinguse">Table 1</a>).</p><p>Note: (1) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>ARSL</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis of this disorder. (2) Testing of ARSL enzymatic activity is not currently available on a clinical basis.</p><p>Molecular genetic testing approaches can include the following:</p><ul><li class="half_rhythm"><div class="half_rhythm">If an Xp <a class="def" href="/books/n/gene/glossary/def-item/deletion-syndrome/">deletion syndrome</a> is suspected (see <a href="#cdp1-xlr.Genetically_Related_Allelic_Dis">Genetically Related Disorders</a>), <b><a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> analysis (CMA)</b> to detect genome-wide large deletions/duplications (including <i>ARSL</i>) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a></div></li><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>ARSL</i> to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>ARSL</i> and other genes of interest (see <a href="#cdp1-xlr.Differential_Diagnosis">Differential Diagnosis</a>) can be considered to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><div id="cdp1-xlr.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Chondrodysplasia Punctata 1, X-Linked</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_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_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>ARSL</i> (formerly <i>ARSE</i>)</td><td headers="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3, 4</sup></td><td headers="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">88% <sup>4</sup></td></tr><tr><td headers="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_cdp1-xlr.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12% <sup>4</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="cdp1-xlr.TF.1.1"><p class="no_margin">See <a href="/books/NBK1544/#cdp1-xlr.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="cdp1-xlr.TF.1.2"><p class="no_margin">See <a href="#cdp1-xlr.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="cdp1-xlr.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="cdp1-xlr.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bk_pop" href="#cdp1-xlr.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="cdp1-xlr.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd></dl></div></div></div></div></div><div id="cdp1-xlr.Clinical_Characteristics"><h2 id="_cdp1-xlr_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cdp1-xlr.Clinical_Description"><h3>Clinical Description</h3><div id="cdp1-xlr.Affected_Males"><h4>Affected Males</h4><p>The most consistent clinical features of <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata 1 (CDPX1) in affected males are chondrodysplasia punctata (CDP), brachytelephalangy, and nasomaxillary hypoplasia. Most affected males have minimal morbidity, and skeletal findings improve by adulthood; however, some have significant medical problems including airway stenosis and cervical spine instability.</p><p>To date, approximately 50 individuals with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ARSL</i> have been reported in the literature. The following description of the phenotypic features associated with this condition is based on the case series from <a class="bk_pop" href="#cdp1-xlr.REF.nino.2008.997">Nino et al [2008]</a> and <a class="bk_pop" href="#cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda et al [2013]</a>.</p><div id="cdp1-xlr.T.chondrodysplasia_punctata_1_x" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Chondrodysplasia Punctata 1, X-Linked: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.chondrodysplasia_punctata_1_x/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.chondrodysplasia_punctata_1_x_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Persons w/Feature <sup>1</sup></th><th id="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_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_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chondrodysplasia punctata (CDP)</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">45/46 <sup>2</sup></td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CDP typically not visible on radiographs after age 3 yrs</td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nasomaxillary hypoplasia</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">42/42</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brachytelephalangy</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33/35</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature (height <5th %ile)</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/16</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postnatal onset</td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Significant respiratory abnormalities</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17/23</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequent respiratory infections, asthma, central apnea, tachypnea, neonatal respiratory distress, mechanical ventilation, tracheotomy, chronic nasal obstruction, nasal stents</td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mixed conductive & sensorineural hearing loss</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13/18</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Significant cervical spine abnormalities</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10/16</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysplasia or hypoplasia of cervical vertebrae, C1–C2 anterior subluxation, kyphosis, cervical cord compression, spinal canal stenosis</td></tr><tr><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Delayed cognitive development</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_cdp1-xlr.T.chondrodysplasia_punctata_1_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="cdp1-xlr.TF.2.1"><p class="no_margin">From <a class="bk_pop" href="#cdp1-xlr.REF.nino.2008.997">Nino et al [2008]</a>, <a class="bk_pop" href="#cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda et al [2013]</a>. Note: These studies may have an ascertainment bias towards more severely affected children.</p></div></dd><dt>2. </dt><dd><div id="cdp1-xlr.TF.2.2"><p class="no_margin">A child with brachytelephalangy, nasomaxillary hypoplasia, and tracheobronchial calcifications did not have CDP at age 14 months [<a class="bk_pop" href="#cdp1-xlr.REF.casarin.2009.2464">Casarin et al 2009</a>].</p></div></dd></dl></div></div></div><p><b>Nasomaxillary hypoplasia.</b> Hypoplasia of the anterior nasal spine results in a characteristic flattened nasal base, reduced nasal tip protrusion with short columella, and in some individuals vertical grooves within the alae nasi. The nostrils are crescent shaped.</p><p><b>Brachytelephalangy.</b> The shortening of the distal phalanges is typically seen in newborns in both hands and feet. Brachytelephalangy persists in the fingers over the life span of individuals with CDPX1 but may become less apparent with age.</p><p><b>Growth</b> measurements tend to be normal at birth; short stature usually develops postnatally but only some affected adults have short stature.</p><p><b>Respiratory insufficiency.</b> Respiratory compromise caused by severe nasal hypoplasia or extensive punctate calcifications along the tracheobronchial tree may require choanal stents, tracheostomy, or tracheal reconstruction [<a class="bk_pop" href="#cdp1-xlr.REF.wolpoe.2004.1423">Wolpoe et al 2004</a>].</p><p><b>Hearing loss.</b> Conductive and sensorineural hearing loss have been reported.</p><p><b>Cervical spine abnormalities.</b> Abnormal ossification of the cervical vertebrae can result in cervical spine stenosis and/or instability and spinal cord compression [<a class="bk_pop" href="#cdp1-xlr.REF.garnier.2007.327">Garnier et al 2007</a>, <a class="bk_pop" href="#cdp1-xlr.REF.vogel.2012.609">Vogel & Menezes 2012</a>].</p><p><b>Developmental delay / intellectual disability.</b> Cognitive delay has been reported in some individuals.</p><p><b>Other.</b> Less frequently seen findings:</p><ul><li class="half_rhythm"><div>Ophthalmologic abnormalities (e.g., cataracts, optic disc atrophy, small optic nerves)</div></li><li class="half_rhythm"><div>Cardiac anomalies (e.g., patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary artery stenosis)</div></li><li class="half_rhythm"><div>Gastroesophageal reflux</div></li><li class="half_rhythm"><div>Feeding difficulties</div></li></ul><p><b>Prognosis.</b> Affected individuals most often have a normal life span; however, some males experience severe morbidity and early mortality due to respiratory compromise, cervical spine stenosis, and/or cervical instability [<a class="bk_pop" href="#cdp1-xlr.REF.brunettipierri.2003.164">Brunetti-Pierri et al 2003</a>, <a class="bk_pop" href="#cdp1-xlr.REF.garnier.2007.327">Garnier et al 2007</a>, <a class="bk_pop" href="#cdp1-xlr.REF.nino.2008.997">Nino et al 2008</a>].</p></div><div id="cdp1-xlr.Heterozygotes"><h4>Heterozygotes</h4><p>Affected <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> females have not been described, presumably because they have sufficient levels of ARSE enzyme activity expressed from both X chromosomes. Some <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> females may have smaller-than-expected stature [<a class="bk_pop" href="#cdp1-xlr.REF.sheffield.1998.1004">Sheffield et al 1998</a>, <a class="bk_pop" href="#cdp1-xlr.REF.brunettipierri.2003.164">Brunetti-Pierri et al 2003</a>].</p></div></div><div id="cdp1-xlr.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been identified.</p></div><div id="cdp1-xlr.Penetrance"><h3>Penetrance</h3><p>Penetrance may be incomplete. <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1544/table/cdp1-xlr.T.notable_arsl_pathogenic_varia/?report=objectonly" target="object" rid-ob="figobcdp1xlrTnotablearslpathogenicvaria">p.Gly137Ala</a> was identified in an affected <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> and his unaffected maternal grandfather [<a class="bk_pop" href="#cdp1-xlr.REF.sheffield.1998.1004">Sheffield et al 1998</a>]. A <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of exons 7-10 was identified in an affected proband and his asymptomatic maternal grandfather [<a class="bk_pop" href="#cdp1-xlr.REF.casarin.2009.2464">Casarin et al 2009</a>]. Considering that physical features of CDPX1 improve with age, it is uncertain whether such instances represent non-<a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a>.</p></div><div id="cdp1-xlr.Nomenclature"><h3>Nomenclature</h3><p>CDPX1 refers specifically to a deficiency of ARSL enzyme activity.</p><p>Brachytelephalangic chondrodysplasia punctata (BCDP) is a descriptive term associated with CDPX1 and its non-genetic phenocopies.</p></div><div id="cdp1-xlr.Prevalence"><h3>Prevalence</h3><p>The prevalence of CDPX1 is unknown; in one study it was estimated at 1:500,000 [<a class="bk_pop" href="#cdp1-xlr.REF.malou.2001.176">Malou et al 2001</a>], but it is likely more common.</p></div></div><div id="cdp1-xlr.Genetically_Related_Allelic_Dis"><h2 id="_cdp1-xlr_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> intragenic pathogenic variants in <i>ARSL</i> (formerly <i>ARSE</i>).</p><p><b>Contiguous Xp <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions that include <i>ARSL</i></b> have additional phenotypic features that may include ichthyosis, hypogonadotropic hypogonadism, anosmia, cataracts, intellectual disability, and autism. Affected males have Xp terminal deletions, interstitial deletions, or translocations (e.g., <a href="/books/n/gene/lwd/">SHOX Deficiency Disorders</a>).</p></div><div id="cdp1-xlr.Differential_Diagnosis"><h2 id="_cdp1-xlr_Differential_Diagnosis_">Differential Diagnosis</h2><div id="cdp1-xlr.Genetic_Disorders"><h3>Genetic Disorders</h3><div id="cdp1-xlr.T.disorders_with_brachytelephal" class="table"><h3><span class="label">Table 3a. </span></h3><div class="caption"><p>Disorders with Brachytelephalangic Chondrodysplasia Punctata (BCDP) in the Differential Diagnosis of CDPX1</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.disorders_with_brachytelephal/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.disorders_with_brachytelephal_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Additional Overlapping Feature</th><th id="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Findings Distinguishing the Disorder from CDPX1</th></tr></thead><tbody><tr><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GGCX</i>
|
||
<br />
|
||
<i>VKORC1</i>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combined deficiency of vitamin K-dependent clotting factor 1 (OMIM <a href="https://omim.org/entry/277450" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">277450</a>) & factor 2 (OMIM <a href="https://omim.org/entry/607473" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">607473</a>)</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nasal hypoplasia</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bleeding disorder due to variably ↓ levels of coagulation factors II, VII, IX, & X, & protein C, protein S, & protein Z</td></tr><tr><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MGP</i>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Keutel syndrome (OMIM <a href="https://omim.org/entry/245150" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">245150</a>)</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_cdp1-xlr.T.disorders_with_brachytelephal_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">More diffuse & progressive calcification of cartilage incl nose, auricles, & respiratory tract</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; CDPX1 = chondrodysplasia punctata 1, <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd></dl></div></div></div><div id="cdp1-xlr.T.disorders_with_nonbrachytelep" class="table"><h3><span class="label">Table 3b. </span></h3><div class="caption"><p>Disorders with Non-Brachytelephalangic Chondrodysplasia Punctata and Cervical Spine Anomalies in the Differential Diagnosis of CDPX1</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.disorders_with_nonbrachytelep/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.disorders_with_nonbrachytelep_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Findings Distinguishing the Disorder from CDPX1</th></tr><tr><th headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4" id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Features</th><th headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4" id="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biochemical Findings</th></tr></thead><tbody><tr><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>AGPS</i>
|
||
<br />
|
||
<i>GNPAT</i>
|
||
<br />
|
||
<i>PEX5</i>
|
||
<br />
|
||
<i>PEX7</i>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/rcdp/">RDCP1</a>, 2, 3, & 5 (OMIM <a href="https://omim.org/phenotypicSeries/PS215100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS215100</a>)</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rhizomelia, profound growth restriction, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cataract</div></li><li class="half_rhythm"><div>Absence of nasal hypoplasia</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Deficiency of peroxisomal plasmalogen (measured in erythrocytes) is diagnostic.</td></tr><tr><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>EBP</i>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/x-dcdp/">CDPX2</a> <sup>1</sup></td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis, & atrophoderma</div></li><li class="half_rhythm"><div>Affected individuals are typically female</div></li><li class="half_rhythm"><div>Absence of nasal hypoplasia</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ 8(9)-cholestenol & 8-dehydrocholesterol levels in plasma</td></tr><tr><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NSDHL</i> <sup>2</sup></td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CHILD syndrome (See <a href="/books/n/gene/nsdhl-dis/"><i>NSDHL</i>-Related Disorders</a>.)</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Male lethal, unilateral CDP, rhizomelia, polydactyly, skin findings; one side of the body affected</div></li><li class="half_rhythm"><div>Absence of nasal hypoplasia</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_1_4 hd_h_cdp1-xlr.T.disorders_with_nonbrachytelep_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ 4-methyl- & carboxysterols levels in cultured lymphoblasts (but only occasionally in plasma) <sup>2</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; CDP = chondrodysplasia punctata; CDPX = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata; CHILD = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> hemidysplasia, ichthyosis, limb defects; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; RCDP = rhizomelic chondrodysplasia punctata; XL = X-linked</p></div></dd><dt>1. </dt><dd><div id="cdp1-xlr.TF.3b.1"><p class="no_margin">Also referred to as Conradi-Hünermann syndrome and Happle syndrome.</p></div></dd><dt>2. </dt><dd><div id="cdp1-xlr.TF.3b.2"><p class="no_margin"><i>NSDHL</i> encodes a cholesterol biosynthetic 4-methylsterol dehydrogenase. The enzyme, part of a 4-methylsterol demethylase complex, occurs one step proximal to the EBP sterol isomerase.</p></div></dd></dl></div></div></div></div><div id="cdp1-xlr.Teratogen_Exposures"><h3>Teratogen Exposures</h3><p>Warfarin embryopathy and other vitamin K deficiencies (including vitamin K epoxide reductase deficiency) are phenotypically similar to CDPX1 with especially severe hypoplasia of the nasal bone ("Binder anomaly"), distal phalangeal abnormalities, and punctata of the axial skeleton.</p><p>BCDP was reported in infants whose mothers had presumed vitamin K deficiency as a result of severe hyperemesis gravidarum [<a class="bk_pop" href="#cdp1-xlr.REF.brunettipierri.2007.200">Brunetti-Pierri et al 2007</a>], Crohn disease [<a class="bk_pop" href="#cdp1-xlr.REF.toriello.2013.417">Toriello et al 2013</a>], small intestinal obstruction [<a class="bk_pop" href="#cdp1-xlr.REF.eash.2003.70">Eash et al 2003</a>], postoperative small bowel syndrome [<a class="bk_pop" href="#cdp1-xlr.REF.menger.1997.129">Menger et al 1997</a>, <a class="bk_pop" href="#cdp1-xlr.REF.khau_van_kien.1998.66">Khau Van Kien et al 1998</a>], untreated celiac disease [<a class="bk_pop" href="#cdp1-xlr.REF.menger.1997.129">Menger et al 1997</a>], pancreatitis [<a class="bk_pop" href="#cdp1-xlr.REF.herman.2002.434">Herman et al 2002</a>], cholelithiasis [<a class="bk_pop" href="#cdp1-xlr.REF.jaillet.2005.188">Jaillet et al 2005</a>], and liver fibrosis due to transfusional iron overload [<a class="bk_pop" href="#cdp1-xlr.REF.xie.2013.e265">Xie et al 2013</a>]. Maternal vitamin K deficiency was indirectly documented in three instances [<a class="bk_pop" href="#cdp1-xlr.REF.khau_van_kien.1998.66">Khau Van Kien et al 1998</a>, <a class="bk_pop" href="#cdp1-xlr.REF.alessandri.2010.85">Alessandri et al 2010</a>, <a class="bk_pop" href="#cdp1-xlr.REF.xie.2013.e265">Xie et al 2013</a>] and suspected in the others. Molecular genetic testing did not identify an <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the infant described by <a class="bk_pop" href="#cdp1-xlr.REF.eash.2003.70">Eash et al [2003]</a>.</p><p>Maternal autoimmune disease (systemic lupus erythematosus) [<a class="bk_pop" href="#cdp1-xlr.REF.blask.2018.979">Blask et al 2018</a>, <a class="bk_pop" href="#cdp1-xlr.REF.alkhunaizi.2020.1807">Alkhunaizi et al 2020</a>], mixed connective tissue disease, and scleroderma [<a class="bk_pop" href="#cdp1-xlr.REF.chitayat.2008.3038">Chitayat et al 2008</a>, <a class="bk_pop" href="#cdp1-xlr.REF.schulz.2010.410">Schulz et al 2010</a>] can cause CDP with rhizomelic limb shortening.</p></div></div><div id="cdp1-xlr.Management"><h2 id="_cdp1-xlr_Management_">Management</h2><div id="cdp1-xlr.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata 1 (CDPX1), the evaluations summarized in <a href="/books/NBK1544/table/cdp1-xlr.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobcdp1xlrTrecommendedevaluationsfollo">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="cdp1-xlr.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Chondrodysplasia Punctata 1, X-Linked</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cdp1-xlr.T.recommended_evaluations_follo_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_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Respiratory</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of upper & lower airways by ENT & pulmonologist</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If stridor is present</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Obstructive sleep</b>
|
||
<br />
|
||
<b>apnea</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polysomnography</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If sleep apnea is suspected</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Growth assessment</div></li><li class="half_rhythm"><div>Skeletal survey</div></li><li class="half_rhythm"><div>Assessment for scoliosis</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To determine extent of CDP & skeletal anomalies</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine</b>
|
||
<br />
|
||
<b>instability</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Flexion, neutral, & extension lateral radiographs of the cervical spine</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cervical spine MRI if clinical evidence of cervical myelopathy or significant instability on radiographs</div></li><li class="half_rhythm"><div>Special consideration when performing this study in flexion & extension positions as spinal cord compression may only occur w/these movements (i.e., normal neutral cervical spine MRI does not rule out dynamic compression).</div></li><li class="half_rhythm"><div>Consider brain MRI at time of cervical spine MRI. <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Audiology</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing assessment</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for sensorineural & conductive hearing loss</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmologic</b>
|
||
<br />
|
||
<b>abnormalities</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for cataracts, optic disc atrophy, & small optic nerves</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac anomalies</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary artery stenosis</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & families re nature, MOI, & implications of CDPX1 in order to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#cdp1-xlr.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CDP = chondrodysplasia punctata; CDPX1 = chondrodysplasia punctata 1, <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="cdp1-xlr.TF.4.1"><p class="no_margin">Although not reported in individuals with CDPX1, cortical dysplasia was reported in two infants with brachytelephalangic chondrodysplasia punctata due to maternal vitamin K deficiency [<a class="bk_pop" href="#cdp1-xlr.REF.brunettipierri.2007.200">Brunetti-Pierri et al 2007</a>, <a class="bk_pop" href="#cdp1-xlr.REF.bhoj.2013.2396">Bhoj et al 2013</a>]. It is suspected that cortical dysplasia could occur in individuals with CDPX1 [Author, personal observation].</p></div></dd><dt>2. </dt><dd><div id="cdp1-xlr.TF.4.2"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="cdp1-xlr.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="cdp1-xlr.T.treatment_of_manifestations_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Chondrodysplasia Punctata 1, X-Linked</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.treatment_of_manifestations_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.treatment_of_manifestations_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.treatment_of_manifestations_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_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th></tr></thead><tbody><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Respiratory difficulty</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per ENT/pulmonologist incl nasal stents & oxygen</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Severe maxillary hypoplasia or maxillary retrognathia</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reconstructive surgery in older individuals as needed <sup>1</sup></td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine instability</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cervical collar or spinal fusion as needed</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine stenosis</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Decompression as needed</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hearing aids</div></li><li class="half_rhythm"><div>Pressure equalization tube placement as needed</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delays</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Adjuvant therapies incl PT, OT, & speech therapy for persons w/identified developmental delays</div></li><li class="half_rhythm"><div>Individualized education plans for learning disorders & school performance issues</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vision issues</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per ophthalmologist</td></tr><tr><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac anomalies</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per cardiologist</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="cdp1-xlr.TF.5.1"><p class="no_margin">
|
||
<a class="bk_pop" href="#cdp1-xlr.REF.carach.2002.82">Carach et al [2002]</a>
|
||
</p></div></dd></dl></div></div></div></div><div id="cdp1-xlr.Surveillance"><h3>Surveillance</h3><div id="cdp1-xlr.T.recommended_surveillance_for" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Chondrodysplasia Punctata 1, X-Linked</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.recommended_surveillance_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.recommended_surveillance_for_lrgtbl__"><table><thead><tr><th id="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cdp1-xlr.T.recommended_surveillance_for_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_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Short stature</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth assessment</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Scoliosis</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment of thoracic & lumbar spine</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine</b>
|
||
<br />
|
||
<b>instability</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Flexion-extension radiograph</div></li><li class="half_rhythm"><div>Flexion-extension MRI if instability & compression on radiographs or limited interpretation on radiographs</div></li></ul>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Every 6-12 mos until growth is completed & prior to anesthesia to assess for cervical spine instability</div></li><li class="half_rhythm"><div>Note: Some individuals have developed cervical spine instability later in the disease course [<a class="bk_pop" href="#cdp1-xlr.REF.vogel.2012.609">Vogel & Menezes 2012</a>].</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing assessment</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ocular abnormalities</b>
|
||
</td><td headers="hd_h_cdp1-xlr.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td></tr></tbody></table></div></div></div><div id="cdp1-xlr.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>In individuals with cervical spine instability, extreme neck extension and neck flexion and contact sports should be avoided.</p><p>In case of general anesthesia, the cervical spine should be assessed by imaging prior to the procedure.</p></div><div id="cdp1-xlr.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 at-risk male relatives of an individual with CDPX1 in order to identify as early as possible those who would benefit from evaluation for cervical spine instability and early screening for cardiac anomalies, ophthalmologic abnormalities, and hearing loss.</p><p>See <a href="#cdp1-xlr.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to evaluation of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="cdp1-xlr.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="cdp1-xlr.Genetic_Counseling"><h2 id="_cdp1-xlr_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="cdp1-xlr.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> chondrodysplasia punctata 1 (CDPX1) is inherited in an X-linked manner.</p></div><div id="cdp1-xlr.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disorder nor will he be <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for the <i>ARSL</i> (formerly <i>ARSE</i>) <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is an <a class="def" href="/books/n/gene/glossary/def-item/obligate-heterozygote/">obligate heterozygote</a> (<a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>). Note: If a woman has more than one affected child and no other affected relatives and if the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in her leukocyte DNA, she most likely has <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li><li class="half_rhythm"><div>If a male is the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case), the mother may be a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> or the affected male may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, in which case the mother is not a carrier.</div></li><li class="half_rhythm"><div>To date, CDPX1 caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has not been reported. All mothers of males with a detectable <i>ARSL</i> pathogenic variant tested to date were found to be carriers [<a class="bk_pop" href="#cdp1-xlr.REF.nino.2008.997">Nino et al 2008</a>, <a class="bk_pop" href="#cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda et al 2013</a>].</div></li></ul><p><b>Sibs of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and have thus far not been affected (see Clinical Description, <a href="#cdp1-xlr.Heterozygotes">Heterozygotes</a>).</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family) and if the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband cannot be detected in the leukocyte DNA of the mother, the risk to sibs is low but greater than that of the general population because of the theoretic possibility of maternal <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p><b>Offspring of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Males with CDPX1 transmit the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> to:</p><ul><li class="half_rhythm"><div>All of their daughters, who will be carriers (heterozygotes) and will not be expected to have clinical manifestations of CDPX1 (affected <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> females have not been reported to date);</div></li><li class="half_rhythm"><div>None of their sons.</div></li></ul><p><b>Other family members.</b> The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s maternal aunts may be at risk of being carriers and the aunts' offspring, depending on their sex, may be at risk of being carriers or of being affected.</p><p>Note: Molecular genetic testing may be able to identify the family member in whom a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> arose, information that could help determine genetic risk status of the extended family.</p></div><div id="cdp1-xlr.Carrier_Detection"><h3>Carrier Detection</h3><p>Molecular genetic testing of at-risk female relatives to determine their genetic status is most informative if the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</p><p>Note: (1) Females who are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> (carriers) for this <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> disorder will usually not be affected. (2) Identification of female heterozygotes requires either (a) prior identification of the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the family or, (b) if an affected male is not available for testing, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> first by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, and if no pathogenic variant is identified, by <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>.</p></div><div id="cdp1-xlr.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#cdp1-xlr.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk male relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> status, and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (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="cdp1-xlr.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the <i>ARSL</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> for CDPX1 are possible.</p><p><b>Ultrasound examination.</b> Abnormal spinal curvature [<a class="bk_pop" href="#cdp1-xlr.REF.he.2019.250">He et al 2019</a>] as well as hypoplastic nose and nasal bone [<a class="bk_pop" href="#cdp1-xlr.REF.nino.2008.997">Nino et al 2008</a>] have been identified on prenatal ultrasound examination in trimesters two and three in affected male fetuses.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. 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="cdp1-xlr.Resources"><h2 id="_cdp1-xlr_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>CDPX1 Family Support Group</b>
|
||
</div><div><b>Email:</b> thegillums@cox.net</div></li><li class="half_rhythm"><div>
|
||
<b>BabyHearing.org</b>
|
||
</div><div>
|
||
<i>This site, developed with support from the National Institute on Deafness and Other Communication Disorders, provides information about newborn hearing screening and hearing loss.</i>
|
||
</div><div>
|
||
<a href="https://www.babyhearing.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">babyhearing.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Human Growth Foundation</b>
|
||
</div><div>
|
||
<a href="https://www.hgfound.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">hgfound.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Little People of America</b>
|
||
</div><div><b>Phone:</b> 888-LPA-2001; 714-368-3689</div><div><b>Fax:</b> 707-721-1896</div><div><b>Email:</b> info@lpaonline.org</div><div>
|
||
<a href="https://www.lpaonline.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">lpaonline.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MAGIC Foundation</b>
|
||
</div><div><b>Phone:</b> 630-836-8200</div><div><b>Email:</b> contactus@magicfoundation.org</div><div>
|
||
<a href="https://www.magicfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">magicfoundation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>UCLA International Skeletal Dysplasia Registry (ISDR)</b>
|
||
</div><div><b>Phone:</b> 310-825-8998</div><div>
|
||
<a href="https://www.uclahealth.org/ortho/isdr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Skeletal Dysplasia Registry</a>
|
||
</div></li></ul>
|
||
</div><div id="cdp1-xlr.Molecular_Genetics"><h2 id="_cdp1-xlr_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 id="cdp1-xlr.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Chondrodysplasia Punctata 1, X-Linked: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cdp1-xlr.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/415" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>ARSL</i>
|
||
</a>
|
||
</td><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=415" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xp22<wbr style="display:inline-block"></wbr>.33</a>
|
||
</td><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P51690" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Arylsulfatase L</a>
|
||
</td><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.LOVD.nl/ARSE" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ARSE @ LOVD</a>
|
||
</td><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ARSL" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ARSL</a>
|
||
</td><td headers="hd_b_cdp1-xlr.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ARSL[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ARSL</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="cdp1-xlr.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="cdp1-xlr.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Chondrodysplasia Punctata 1, X-Linked (<a href="/omim/300180,302950" 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/NBK1544/table/cdp1-xlr.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/300180" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300180</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ARYLSULFATASE L; ARSL</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/302950" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">302950</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CHONDRODYSPLASIA PUNCTATA 1, X-LINKED RECESSIVE; CDPX1</td></tr></tbody></table></div></div><div id="cdp1-xlr.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ARSL</i> encode arylsulfatase L (ARSE), a sulfatase that localizes to Golgi membranes [<a class="bk_pop" href="#cdp1-xlr.REF.daniele.1998.562">Daniele et al 1998</a>]. Sulfatase enzymes hydrolyze sulfate ester bonds in glycosaminoglycans, sulfolipids, steroid sulfates, and other compounds. All sulfatases undergo a post-translational processing event by the enzyme SUMF1 in which a C-alpha-formylglycine (FGly) is generated from a cysteine [<a class="bk_pop" href="#cdp1-xlr.REF.cosma.2003.445">Cosma et al 2003</a>].</p><p>Although its physiologic substrate has not yet been identified, ARSE enzyme activity is inhibited in vitro by the anticoagulant warfarin [<a class="bk_pop" href="#cdp1-xlr.REF.rost.2004.537">Rost et al 2004</a>]. Given the well-documented phenotypic similarities between CDPX1 and warfarin embryopathy, ARSE may be the enzyme inhibited by warfarin.</p><p><b>Mechanism of disease causation.</b> The majority of <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants studied showed negligible activity using a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> expression system and the artificial substrate, fluorogenic 4-methylumbelliferyl (4-MU) sulfate [<a class="bk_pop" href="#cdp1-xlr.REF.daniele.1998.562">Daniele et al 1998</a>, <a class="bk_pop" href="#cdp1-xlr.REF.brunettipierri.2003.164">Brunetti-Pierri et al 2003</a>, <a class="bk_pop" href="#cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda et al 2013</a>]. Individuals with <i>ARSL</i> gene deletions, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> variants, or missense variants present with indistinguishable phenotypes, supporting loss of function as the disease mechanism [<a class="bk_pop" href="#cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda et al 2013</a>].</p><p><b><i>ARSL</i>-specific laboratory technical considerations.</b>
|
||
<i>ARSL</i> has a <a class="def" href="/books/n/gene/glossary/def-item/pseudogene/">pseudogene</a> on the Y <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a>, which may complicate detection of <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>-level deletions for some exons.</p><div id="cdp1-xlr.T.notable_arsl_pathogenic_varia" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>ARSL</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1544/table/cdp1-xlr.T.notable_arsl_pathogenic_varia/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cdp1-xlr.T.notable_arsl_pathogenic_varia_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_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_cdp1-xlr.T.notable_arsl_pathogenic_varia_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_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000047.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000047<wbr style="display:inline-block"></wbr>.2</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000038.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000038<wbr style="display:inline-block"></wbr>.2</a>
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</td><td headers="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.410G>C</td><td headers="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly137Ala</td><td headers="hd_h_cdp1-xlr.T.notable_arsl_pathogenic_varia_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incomplete <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> reported in one family [<a class="bk_pop" href="#cdp1-xlr.REF.sheffield.1998.1004">Sheffield et al 1998</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><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><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/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="cdp1-xlr.Chapter_Notes"><h2 id="_cdp1-xlr_Chapter_Notes_">Chapter Notes</h2><div id="cdp1-xlr.Author_History"><h3>Author History</h3><p>Michael B Bober, MD, PhD (2008-present)<br />Nancy E Braverman, MS, MD (2008-present)<br />Nicola Brunetti-Pierri, MD (2008-present)<br />Gretchen L Oswald, MS, CGC; Johns Hopkins Medical Center (2008-2020)<br />Sharon F Suchy, PhD (2020-present)</p></div><div id="cdp1-xlr.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>15 October 2020 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>20 November 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>3 November 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>22 April 2008 (me) Review posted live</div></li><li class="half_rhythm"><div>16 November 2007 (nb) Original submission</div></li></ul></div></div><div id="cdp1-xlr.References"><h2 id="_cdp1-xlr_References_">References</h2><div id="cdp1-xlr.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.alkhunaizi.2020.1807">Alkhunaizi E, Unger S, Shannon P, Nishimura G, Blaser S, Chitayat D. Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants. <span><span class="ref-journal">Am J Med Genet A. </span>2020;<span class="ref-vol">182</span>:1807–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32506814" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32506814</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.alessandri.2010.85">Alessandri JL, Ramful D, Cuillier F. Binder phenotype and brachytelephalangic chondrodysplasia punctata secondary to maternal vitamin K deficiency. <span><span class="ref-journal">Clin Dysmorphol. </span>2010;<span class="ref-vol">19</span>:85–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20177377" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20177377</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.bhoj.2013.2396">Bhoj E, Dubbs H, McDonald-McGinn D, Zackai E. Late-onset partial complex seizures secondary to cortical dysplasia in a patient with maternal vitamin K deficient embryopathy: comments on the article by Toriello et al [2013] and first report of the natural history. <span><span class="ref-journal">Am J Med Genet A. </span>2013;<span class="ref-vol">161A</span>:2396–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23897629" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23897629</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.blask.2018.979">Blask AR, Rubio EI, Chapman KA, Lawrence AK, Bulas DI. Severe nasomaxillary hypoplasia (Binder phenotype) on prenatal US/MRI: an important marker for the prenatal diagnosis of chondrodysplasia punctata. <span><span class="ref-journal">Pediatr Radiol. </span>2018;<span class="ref-vol">48</span>:979–91.</span> [<a href="/pmc/articles/PMC6365632/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6365632</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29572747" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29572747</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.brunettipierri.2003.164">Brunetti-Pierri N, Andreucci MV, Tuzzi R, Vega GR, Gray G, McKeown C, Ballabio A, Andria G, Meroni G, Parenti G. X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability. <span><span class="ref-journal">Am J Med Genet A. </span>2003;<span class="ref-vol">117A</span>:164–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12567415" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12567415</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.brunettipierri.2007.200">Brunetti-Pierri N, Hunter JV, Boerkoel CF. Gray matter heterotopias and brachytelephalangic chondrodysplasia punctata: a complication of hyperemesis gravidarum induced vitamin K deficiency? <span><span class="ref-journal">Am J Med Genet A. </span>2007;<span class="ref-vol">143A</span>:200–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17163521" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17163521</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.carach.2002.82">Carach B, Woods M, Scott P. Maxillonasal dysplasia (Binder syndrome): a lateral cephalometric assessment. <span><span class="ref-journal">Aust Orthod J. </span>2002;<span class="ref-vol">18</span>:82–91.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12462685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12462685</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.casarin.2009.2464">Casarin A, Rusalen F, Doimo M, Trevisson E, Carraro S, Clementi M, Tenconi R, Baraldi E, Salviati L. X-linked brachytelephalangic chondrodysplasia punctata: a simple trait that is not so simple. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:2464–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19839041" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19839041</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.chitayat.2008.3038">Chitayat D, Keating S, Zand DJ, Costa T, Zackai EH, Silverman E, Tiller G, Unger S, Miller S, Kingdom J, Toi A, Curry CJ. Chondrodysplasia punctata associated with maternal autoimmune diseases: expanding the spectrum from systemic lupus erythematosus (SLE) to mixed connective tissue disease (MCTD) and scleroderma report of eight cases. <span><span class="ref-journal">Am J Med Genet A. </span>2008;<span class="ref-vol">146A</span>:3038–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19006208" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19006208</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.cosma.2003.445">Cosma MP, Pepe S, Annunziata I, Newbold RF, Grompe M, Parenti G, Ballabio A. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. <span><span class="ref-journal">Cell. </span>2003;<span class="ref-vol">113</span>:445–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12757706" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12757706</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.daniele.1998.562">Daniele A, Parenti G, d'Addio M, Andria G, Ballabio A, Meroni G. Biochemical characterization of arylsulfatase E and functional analysis of mutations found in patients with X-linked chondrodysplasia punctata. <span><span class="ref-journal">Am J Hum Genet. </span>1998;<span class="ref-vol">62</span>:562–72.</span> [<a href="/pmc/articles/PMC1376941/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1376941</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9497243" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9497243</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.eash.2003.70">Eash DD, Weaver DD, Brunetti-Pierri N. Cervical spine stenosis and possible vitamin K deficiency embryopathy in an unusual case of chondrodysplasia punctata and an updated classification system. <span><span class="ref-journal">Am J Med Genet A. </span>2003;<span class="ref-vol">122A</span>:70–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12949976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12949976</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.garnier.2007.327">Garnier A, Dauger S, Eurin D, Parisi I, Parenti G, Garel C, Delbecque K, Baumann C. Brachytelephalangic chondrodysplasia punctata with severe spinal cord compression: report of four new cases. <span><span class="ref-journal">Eur J Pediatr. </span>2007;<span class="ref-vol">166</span>:327–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16937129" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16937129</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.he.2019.250">He G, Yin Y, Zhao J, et al. Prenatal findings in a fetus with X-linked recessive type of chondrodysplasia punctata (CDPX1): a case report with novel mutation. <span><span class="ref-journal">BMC Pediatr. </span>2019;<span class="ref-vol">19</span>:250.</span> [<a href="/pmc/articles/PMC6647267/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6647267</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31337364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31337364</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.herman.2002.434">Herman GE, Kelley RI, Pureza V, Smith D, Kopacz K, Pitt J, Sutphen R, Sheffield LJ, Metzenberg AB. Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome). <span><span class="ref-journal">Genet Med. </span>2002;<span class="ref-vol">4</span>:434–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12509714" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12509714</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.jaillet.2005.188">Jaillet J, Robert-Gnansia E, Till M, Vinciguerra C, Edery P. Biliary lithiasis in early pregnancy and abnormal development of facial and distal limb bones (Binder syndrome): a possible role for vitamin K deficiency. <span><span class="ref-journal">Birth Defects Res A Clin Mol Teratol. </span>2005;<span class="ref-vol">73</span>:188–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15751048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15751048</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.khau_van_kien.1998.66">Khau Van Kien P, Nievelon-Chevallier A, Spagnolo G, Douvier S, Maingueneau C. Vitamin K deficiency embriopathy. <span><span class="ref-journal">Am J Med Genet. </span>1998;<span class="ref-vol">79</span>:66–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9738872" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9738872</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.malou.2001.176">Malou E, Gekas J, Troucelier-Lucas V, Mornet E, Razafimanantsoa L, Cuvelier B, Mathieu M, Thepot F. X-linked recessive chondrodysplasia punctata. Cytogenetic study and role of molecular biology. <span><span class="ref-journal">Arch Pediatr. </span>2001;<span class="ref-vol">8</span>:176–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11232459" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11232459</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.matosmiranda.2013.650">Matos-Miranda C, Nimmo G, Williams B, Tysoe C, Owens M, Bale S, Braverman N. A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies. <span><span class="ref-journal">Genet Med. </span>2013;<span class="ref-vol">15</span>:650–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23470839" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23470839</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.menger.1997.129">Menger H, Lin AE, Toriello HV, Bernert G, Spranger JW. Vitamin K deficiency embryopathy: a phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism. <span><span class="ref-journal">Am J Med Genet. </span>1997;<span class="ref-vol">72</span>:129–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9382132" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9382132</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.nino.2008.997">Nino M, Matos-Miranda C, Maeda M, Chen L, Allanson J, Armour C, Greene C, Kamaluddeen M, Rita D, Medne L, Zackai E, Mansour S, Superti-Furga A, Lewanda A, Bober M, Rosenbaum K, Braverman N. Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata. <span><span class="ref-journal">Am J Med Genet A. </span>2008;<span class="ref-vol">146A</span>:997–1008.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18348268" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18348268</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.rost.2004.537">Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. <span><span class="ref-journal">Nature. </span>2004;<span class="ref-vol">427</span>:537–41.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14765194" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14765194</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.schulz.2010.410">Schulz SW, Bober M, Johnson C, Braverman N, Jimenez SA. Maternal mixed connective tissue disease and offspring with chondrodysplasia punctata. <span><span class="ref-journal">Semin Arthritis Rheum. </span>2010;<span class="ref-vol">39</span>:410–6.</span> [<a href="/pmc/articles/PMC2844477/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2844477</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19110299" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19110299</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.sheffield.1998.1004">Sheffield LJ, Osborn AH, Hutchison WM, Sillence DO, Forrest SM, White SJ, Dahl HH. Segregation of mutations in arylsulphatase E and correlation with the clinical presentation of chondrodysplasia punctata. <span><span class="ref-journal">J Med Genet. </span>1998;<span class="ref-vol">35</span>:1004–8.</span> [<a href="/pmc/articles/PMC1051512/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1051512</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9863597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9863597</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.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></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.toriello.2013.417">Toriello HV, Erick M, Alessandri JL, Bailey D, Brunetti-Pierri N, Cox H, Fryer A, Marty D, McCurdy C, Mulliken JB, Murphy H, Omlor J, Pauli RM, Ranells JD, Sanchez-Valle A, Tobiasz A, Van Maldergem L, Lin AE. Maternal vitamin K deficient embryopathy: association with hyperemesis gravidarum and Crohn disease. <span><span class="ref-journal">Am J Med Genet A. </span>2013;<span class="ref-vol">161A</span>:417–29.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23404932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23404932</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.vogel.2012.609">Vogel TW, Menezes AH. Natural history and management of cervical spine disease in chondrodysplasia punctata and coumarin embryopathy. <span><span class="ref-journal">Childs Nerv Syst. </span>2012;<span class="ref-vol">28</span>:609–19.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22274407" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22274407</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.wolpoe.2004.1423">Wolpoe ME, Braverman N, Lin SY. Severe tracheobronchial stenosis in the X-linked recessive form of chondrodysplasia punctata. <span><span class="ref-journal">Arch Otolaryngol Head Neck Surg. </span>2004;<span class="ref-vol">130</span>:1423–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15611404" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15611404</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cdp1-xlr.REF.xie.2013.e265">Xie Y, Pivnick EK, Cohen HL, Adams-Graves PE, Pourcyrous M, Aygun B, Hankins JS. Phenocopy of warfarin syndrome in an infant born to a mother with sickle cell anemia and severe transfusional iron overload. <span><span class="ref-journal">J Pediatr Hematol Oncol. </span>2013;<span class="ref-vol">35</span>:e265–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23018567" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23018567</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1544/?report=reader">PubReader</a></li><li><a href="/books/NBK1544/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1544" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1544" style="display:none" title="Cite this Page"><div class="bk_tt">Braverman NE, Bober MB, Brunetti-Pierri N, et al. 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