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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="ATP6V0A2-Related Cutis Laxa" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/03/16" /><meta name="citation_author" content="Lionel Van Maldergem" /><meta name="citation_author" content="William Dobyns" /><meta name="citation_author" content="Uwe Kornak" /><meta name="citation_pmid" content="20301755" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK5200/" /><meta name="citation_keywords" content="ATP6V0A2-CDG" /><meta name="citation_keywords" content="Autosomal Recessive Cutis Laxa Type 2A (ARCL2A)" /><meta name="citation_keywords" content="Autosomal Recessive Cutis Laxa Type 2A (ARCL2A)" /><meta name="citation_keywords" content="ATP6V0A2-CDG" /><meta name="citation_keywords" content="Debré-Type Cutis Laxa" /><meta name="citation_keywords" content="Wrinkly Skin Syndrome" /><meta name="citation_keywords" content="V-type proton ATPase 116 kDa subunit a 2" /><meta name="citation_keywords" content="ATP6V0A2" /><meta name="citation_keywords" content="ATP6V0A2-Related Cutis Laxa" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="ATP6V0A2-Related Cutis Laxa" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Lionel Van Maldergem" /><meta name="DC.Contributor" content="William Dobyns" /><meta name="DC.Contributor" content="Uwe Kornak" /><meta name="DC.Date" content="2023/03/16" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK5200/" /><meta name="description" content="ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression." /><meta name="og:title" content="ATP6V0A2-Related Cutis Laxa" /><meta name="og:type" content="book" /><meta name="og:description" content="ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. 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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="#__NBK5200_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK5200_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/rapid-odp/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/menkes/" 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="_NBK5200_"><span class="title" itemprop="name"><i>ATP6V0A2</i>-Related Cutis Laxa</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: ATP6V0A2-CDG, Autosomal Recessive Cutis Laxa Type 2A (ARCL2A)</div><p class="contrib-group"><span itemprop="author">Lionel Van Maldergem</span>, MD, PhD, <span itemprop="author">William Dobyns</span>, MD, and <span itemprop="author">Uwe Kornak</span>, MD, PhD.</p><a data-jig="ncbitoggler" href="#__NBK5200_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK5200_ai__"><div class="contrib half_rhythm"><span itemprop="author">Lionel Van Maldergem</span>, MD, PhD<div class="affiliation small">Centre de génétique humaine<br />Université de Franche-Comté<br />Besançon, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.orpyks@dlamv" class="oemail">eb.orpyks@dlamv</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">William Dobyns</span>, MD<div class="affiliation small">Seattle Children's Research Institute<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wu@dbw" class="oemail">ude.wu@dbw</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Uwe Kornak</span>, MD, PhD<div class="affiliation small">Institut für Humangenetik<br />Universitätsmedizin Göttingen<br />Göttingen, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.negnitteog-inu.dem@kanrok.ewu" class="oemail">ed.negnitteog-inu.dem@kanrok.ewu</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">March 19, 2009</span>; Last Revision: <span itemprop="dateModified">March 16, 2023</span>.</p><p><em>Estimated reading time: 19 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cutis-laxa.Summary" itemprop="description"><h2 id="_cutis-laxa_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>ATP6V0A2</i>-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>ATP6V0A2</i>-related cutis laxa is established by the presence of suggestive findings and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>ATP6V0A2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Standard treatment for <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> hip dislocation, inguinal hernias, high myopia, and seizure disorders. Early intervention and management of developmental delays and intellectual disability and psychological help as needed for self-image issues.</p><p><i>Surveillance:</i> Annual ophthalmologic examination, EEG, and monitoring of anticonvulsive drug levels.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>ATP6V0A2</i>-related cutis laxa is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier. Once the <i>ATP6V0A2</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> for at-risk relatives, <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 <i>ATP6V0A2-</i>related cutis laxa are possible.</p></div></div><div id="cutis-laxa.GeneReview_Scope"><h2 id="_cutis-laxa_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div id="cutis-laxa.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.Tc_lrgtbl__"><table><thead><tr><th id="hd_h_cutis-laxa.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATP6V0A2</i>-Related Cutis Laxa: Included Phenotypes</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Debré-type cutis laxa</div></li><li class="half_rhythm"><div>Wrinkly skin syndrome</div></li></ul>
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</td></tr></tbody></table></div></div></div><div id="cutis-laxa.Diagnosis"><h2 id="_cutis-laxa_Diagnosis_">Diagnosis</h2><div id="cutis-laxa.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>ATP6V0A2</i>-related cutis laxa, also known as <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> cutis laxa type 2A (ARCL2A), <b>should be considered</b> in individuals with the following findings.</p><div id="cutis-laxa.Clinical_Findings"><h4>Clinical Findings</h4><p>
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<b>Characteristic signs of cutis laxa</b>
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</p><ul><li class="half_rhythm"><div>Furrowing of the skin of the whole body; particularly obvious in neck, axillae, and groin</div></li><li class="half_rhythm"><div>Skin that when extended does not display marked hyperelasticity (as is observed in the Ehlers-Danlos syndromes) but rather maintains its consistency</div></li><li class="half_rhythm"><div>Droopy skin on the cheeks of the face and marked nasolabial folds, giving rise to distinctive facial features that also include prominent nasal root and downslanted palpebral fissures</div></li></ul><p>
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<b>Other evidence of a generalized connective tissue disorder</b>
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</p><ul><li class="half_rhythm"><div>Enlarged fontanelles (i.e., delayed closure of the fontanelles) manifest in newborns (anterior fontanelle >6x6 cm in the newborn; >3x3 cm at age 1 year)</div></li><li class="half_rhythm"><div>Congenital dislocation of the hips</div></li><li class="half_rhythm"><div>Inguinal hernias</div></li><li class="half_rhythm"><div>High myopia</div></li><li class="half_rhythm"><div>Bruch's membrane rupture, cataracts, corneal clouding (infrequent)</div></li></ul></div><div id="cutis-laxa.Laboratory_Findings"><h4>Laboratory Findings</h4><p><b>Serum sialotransferrin <a class="def" href="/books/n/gene/glossary/def-item/isoelectric-focusing/">isoelectric focusing</a> (IEF)</b> reveals the following findings in <i>ATP6V0A2</i>-related cutis laxa:</p><ul><li class="half_rhythm"><div>Reduction of the main protein band, which corresponds to transferrin containing four sialic acid residues</div></li><li class="half_rhythm"><div>Increased amounts of disialo- and trisialo-transferrin that indicate altered N-glycosylation over the normal ranges of:</div><ul><li class="half_rhythm"><div>Disialotransferrin: 2.5%-9.8%</div></li><li class="half_rhythm"><div>Trisialotransferrin: 3.4%-13.7%</div></li></ul></li></ul><p>Note: (1) These findings are also observed in type 2 <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> disorder of glycosylation (CDG type 2) [<a class="bk_pop" href="#cutis-laxa.REF.morava.2005.414">Morava et al 2005</a>, <a class="bk_pop" href="#cutis-laxa.REF.wopereis.2005.156">Wopereis et al 2005</a>, <a class="bk_pop" href="#cutis-laxa.REF.morava.2008.28">Morava et al 2008</a>, <a class="bk_pop" href="#cutis-laxa.REF.guillard.2009.903">Guillard et al 2009</a>]. (2) In the authors' experience, all probands had a CDG type 2 sialotransferrin IEF pattern; however, it has been observed that infants may have a normal transferrin isofocusing profile in the first months of life, but develop the typical transferrin abnormality later on. In these infants, the apolipoprotein C-III isofocusing was already abnormal in the first months of life [<a class="bk_pop" href="#cutis-laxa.REF.morava.2005.414">Morava et al 2005</a>, <a class="bk_pop" href="#cutis-laxa.REF.wopereis.2005.156">Wopereis et al 2005</a>].</p><p><b>Serum apolipoprotein C III IEF</b> reveals the following changes of altered O-glycosylation:</p><ul><li class="half_rhythm"><div>Reduction of the main protein band, which corresponds to apolipoprotein CIII containing two sialic acid residues</div></li><li class="half_rhythm"><div>Increased amounts of monosialotransferrin. Normal ranges depend on age; in adults:</div><ul><li class="half_rhythm"><div>Monosialotransferrin: 43%-69%</div></li><li class="half_rhythm"><div>Disialotransferrin: 23%-50%</div></li></ul></li></ul><p>Note: Abnormal O-glycosylation is supportive of the diagnosis, but a normal or inconclusive result does not eliminate the possibility of <i>ATP6V0A2</i>-related cutis laxa. In the authors' experience, comparing the findings in the parents with those of the index case is most helpful in identifying the reduction of the main band.</p><p><b>Skin biopsy with orcein staining</b> reveals the following:</p><ul><li class="half_rhythm"><div class="half_rhythm">Light microscopy is normal.</div></li><li class="half_rhythm"><div class="half_rhythm">Electron microscopy (EM) shows rarefaction and fragmentation of the elastin network in which elastic fibers are small and misshapen. Within these fibers both elastin and elastofibrils can be distinguished based on their different densities [<a class="bk_pop" href="#cutis-laxa.REF.beyens.2019b.1142">Beyens et al 2019b</a>].</div><div class="half_rhythm">Note: EM studies require a high level of expertise and are only available in specialized centers.</div><div class="half_rhythm">The EM findings strongly support but are not specific for the diagnosis of <i>ATP6V0A2</i>-related cutis laxa.</div></li></ul></div><div id="cutis-laxa.Imaging_Findings"><h4>Imaging Findings</h4><p><b>Central nervous system (CNS) abnormalities.</b> In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Cortical malformation.</b> Abnormally thick (5-10 mm) cortex has subtle vertical streaks that appear smooth in some areas and irregular in others, resembling either lissencephaly or polymicrogyria.</div><div class="half_rhythm">This cortical malformation differs from lissencephaly and polymicrogyria by a consistent and predominant bilateral, symmetric, and frontal distribution that is more severe in the posterior portion of the frontal lobe and the anterior portion of the parietal lobes (including the perisylvian cortex) and less severe in the anterior portion of the frontal lobe and often the superior portion of the temporal lobe. No well-defined microgyri are seen, which also distinguishes the disorder from true polymicrogyria.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Cerebellar malformation</b> ranges from mild cerebellar vermis hypoplasia to classic Dandy-Walker malformation, including severe hypoplasia and upward rotation of the vermis, cystic enlargement of the fourth ventricle, and enlarged posterior fossa.</div></li></ul></div><div id="cutis-laxa.Family_History"><h4>Family History</h4><p>Family history is consistent with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance (e.g., affected sibs and/or parental <a class="def" href="/books/n/gene/glossary/def-item/consanguinity/">consanguinity</a>). Absence of a known family history does not preclude the diagnosis.</p></div></div><div id="cutis-laxa.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>ATP6V0A2</i>-related cutis laxa <b>is established</b> by the presence of <a href="#cutis-laxa.Suggestive_Findings">suggestive findings</a> and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>ATP6V0A2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK5200/table/cutis-laxa.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobcutislaxaTmoleculargenetictestingu">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bk_pop" href="#cutis-laxa.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>ATP6V0A2</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and one <i>ATP6V0A2</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Because the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of <i>ATP6V0A2</i>-related cutis laxa may be indistinguishable from many other inherited disorders with cutis laxa, recommended <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches include use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> or <b>comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b>.</p><p>Note: Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing (<a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> of <i>ATP6V0A2</i>, followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>) is rarely useful and typically NOT recommended.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>A cutis laxa or connective tissue disorder or <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> disorder of glycosylation <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>ATP6V0A2</i> and other genes of interest (see <a href="#cutis-laxa.Differential_Diagnosis">Differential Diagnosis</a>) is most likely 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><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div id="cutis-laxa.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>ATP6V0A2</i>-Related Cutis Laxa</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATP6V0A2</i>
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</td><td headers="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>95% <sup>4</sup></td></tr><tr><td headers="hd_h_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">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_cutis-laxa.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare <sup>4, 6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="cutis-laxa.TF.1.1"><p class="no_margin">See <a href="/books/NBK5200/#cutis-laxa.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="cutis-laxa.TF.1.2"><p class="no_margin">See <a href="#cutis-laxa.Molecular_Genetics">Molecular Genetics</a> for information on 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="cutis-laxa.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="cutis-laxa.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="#cutis-laxa.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="cutis-laxa.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><dt>6. </dt><dd><div id="cutis-laxa.TF.1.6"><p class="no_margin"><a class="bk_pop" href="#cutis-laxa.REF.hucthagowder.2009.2149">Hucthagowder et al [2009]</a> identified <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 16 in four unrelated individuals of Middle Eastern origin in their cohort of 17 affected individuals from 16 families. <a class="bk_pop" href="#cutis-laxa.REF.jones.2013.78">Jones et al [2013]</a> described a deletion of exon 9. A deletion of the whole <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> was identified by <a class="bk_pop" href="#cutis-laxa.REF.gardeitchik.2014.888">Gardeitchik et al [2014]</a>.</p></div></dd></dl></div></div></div></div></div><div id="cutis-laxa.Clinical_Characteristics"><h2 id="_cutis-laxa_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cutis-laxa.Clinical_Description"><h3>Clinical Description</h3><p><i>ATP6V0A2</i>-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI.</p><p>This disorder spans a phenotypic spectrum that includes the historical diagnoses of Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end; these two phenotypes were thought to be distinct clinical entities until their molecular genetic nature was determined. Children diagnosed in the past with Debré-type cutis laxa had more severe developmental and neurologic abnormalities and a less severe cutaneous <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> than children diagnosed with wrinkly skin syndrome, in whom the skin showed tighter wrinkles and the changes in facial features were milder [<a class="bk_pop" href="#cutis-laxa.REF.algazali.2001.213">Al-Gazali et al 2001</a>].</p><p>To date, about 80 individuals have been identified with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ATP6V0A2</i> [<a class="bk_pop" href="#cutis-laxa.REF.morlino.2021.955">Morlino et al 2021</a>; Authors, unpublished observations]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="cutis-laxa.T.atp6v0a2related_cutis_laxa" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>ATP6V0A2</i>-Related Cutis Laxa: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.atp6v0a2related_cutis_laxa/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.atp6v0a2related_cutis_laxa_lrgtbl__"><table><thead><tr><th id="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_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_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cutis laxa</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combination of fine wrinkles & sagging skin; can vanish during childhood.</td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prominent nasal root</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Downslanted palpebral fissures</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Recognizable facial dysmorphism</td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Enlarged fontanels w/delayed closure</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital dislocation of hips</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Inguinal hernia</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">High myopia</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other ophthalmic issues</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay /<br />Intellectual disability</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Always speech delay; some can attend normal school</td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizure disorder</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset variable; may occur as late as adolescence</td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic decline</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possibly up to 40%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unclear; few w/follow-up data</td></tr><tr><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abnormal brain imaging</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td><td headers="hd_h_cutis-laxa.T.atp6v0a2related_cutis_laxa_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain malformation experts can make diagnosis from MRI.</td></tr></tbody></table></div></div><p><b>Presentation and progression.</b> At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. In <i>ATP6V0A2</i>-related cutis laxa the skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some [<a class="bk_pop" href="#cutis-laxa.REF.greally.2014.1245">Greally et al 2014</a>]. Adults with this disorder can show progressive neurologic issues.</p><p><b>Skin findings.</b> Findings of cutis laxa include:</p><ul><li class="half_rhythm"><div>Facial features</div><ul><li class="half_rhythm"><div>Droopy skin on cheeks</div></li><li class="half_rhythm"><div>Prominent nasal bridge</div></li><li class="half_rhythm"><div>Premature aged appearance</div></li><li class="half_rhythm"><div>Downslanting palpebral fissures</div></li><li class="half_rhythm"><div>In most, borderline microcephaly with head circumference 2-3 standard deviations below the mean</div></li></ul></li><li class="half_rhythm"><div>Findings of a generalized connective tissue disorder including:</div><ul><li class="half_rhythm"><div>Enlarged fontanels</div></li><li class="half_rhythm"><div>Congenital dislocation of the hips</div></li><li class="half_rhythm"><div>Inguinal hernia</div></li><li class="half_rhythm"><div>Heart valve dysplasia and/or widening of aortic root</div></li><li class="half_rhythm"><div>Scoliosis</div></li><li class="half_rhythm"><div>Joint laxity</div></li></ul></li></ul><p><b>Ophthalmologic concerns.</b> High myopia (>-5 diopters) has been observed in the majority of affected individuals.</p><ul><li class="half_rhythm"><div>One Portuguese individual had an unclassified corneal dysplasia requiring engraftment.</div></li><li class="half_rhythm"><div>A Belgian individual had unilateral rupture of Bruch's membrane.</div></li><li class="half_rhythm"><div>Strabismus has been observed in nearly half of individuals.</div></li></ul><p><b>Developmental delay.</b> Nearly all affected children described to date have had delayed developmental milestones (especially speech delay) and intellectual disability. Despite delays in developmental milestones and language, affected children are said to be cheerful and outgoing.</p><p>
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<b>Neurologic findings</b>
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</p><ul><li class="half_rhythm"><div><b>Cognitive.</b> Many children have a degenerative course including cognitive decline that begins about the end of the first decade.</div></li><li class="half_rhythm"><div><b>Seizures.</b> Generalized or partial complex seizures begin between ages eight and 12 years.</div></li><li class="half_rhythm"><div><b>Neurologic regression</b> (with or without seizures) can include spasticity and cerebellar signs and symptoms (ataxia, slurred speech). Some adolescents become wheelchair bound. A unique individual with mild brain dysgenesis and compound heterozygosity for <i>ATP6V0A2</i> pathogenic variants had a normal IQ with no history of seizures, and was doing well in mainstream school at age 15 years [<a class="bk_pop" href="#cutis-laxa.REF.van_maldergem.2008.1602">Van Maldergem et al 2008</a>].</div></li></ul><p><b>Abnormal brain imaging.</b> Cortical and/or cerebellar abnormality is identified in most individuals on brain MRI. See Suggestive Findings, <a href="#cutis-laxa.Imaging_Findings">Imaging Findings</a>.</p><p><b>Other.</b> Bleeding disorder linked to coagulation factor deficiencies may occur [<a class="bk_pop" href="#cutis-laxa.REF.beyens.2019b.1142">Beyens et al 2019b</a>].</p></div><div id="cutis-laxa.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> are known.</p></div><div id="cutis-laxa.Prevalence"><h3>Prevalence</h3><p>The prevalence of all types of cutis laxa is 1:4,000,000 according to Rhône-Alpes Eurocat registry [E Robert, personal observation]. It is the second- to third-most common form of <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> cutis laxa.</p></div></div><div id="cutis-laxa.Genetically_Related_Allelic_D"><h2 id="_cutis-laxa_Genetically_Related_Allelic_D_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>ATP6V0A2</i>.</p></div><div id="cutis-laxa.Differential_Diagnosis"><h2 id="_cutis-laxa_Differential_Diagnosis_">Differential Diagnosis</h2><p>Other disorders characterized by cutis laxa are summarized in <a href="/books/NBK5200/table/cutis-laxa.T.disorders_to_consider_in_th/?report=objectonly" target="object" rid-ob="figobcutislaxaTdisorderstoconsiderinth">Table 3</a>.</p><div id="cutis-laxa.T.disorders_to_consider_in_th" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Disorders to Consider in the Differential Diagnosis of <i>ATP6V0A2</i>-Related Cutis Laxa</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.disorders_to_consider_in_th/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.disorders_to_consider_in_th_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" colspan="5" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Findings</th><th id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" style="text-align:left;vertical-align:middle;">Comment</th></tr><tr><th headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Cutis laxa</th><th headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Emphysema</th><th headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Aneurysms</th><th headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID/DD</th><th headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4" id="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bladder<br />diverticulae</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ALDH18A1</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">De Barsy syndrome A (ARCL3A) (OMIM <a href="https://www.omim.org/entry/219150" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">219150</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID (variable), translucent skin</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">ADCL3 (OMIM <a href="https://www.omim.org/entry/616603" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616603</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID (variable), translucent skin</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ATP6V1A</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ARCL2D (OMIM <a href="https://omim.org/entry/617403" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617403</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Facial appearance similar to ARCL2A; myopathy; respiratory problems in infancy can be lethal; no seizures; often no ID. Like ARCL2A, ARCL2D & ARCL2C are CDGs.</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ATP6V1E1</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ARCL2C (OMIM <a href="https://omim.org/entry/617402" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617402</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>EFEMP2</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/efemp2-cutis-laxa/"><i>EFEMP2</i>-related cutis laxa</a>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ELN</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/eln-cutis-laxa/"><i>ELN</i>-related cutis laxa</a> (ADCL1)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>EMILIN1</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>EMILIN1</i>-related cutis laxa <sup>1</sup></td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bone fragility, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies of kidney & urinary tract</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FBLN5</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/fbln5-cutis-laxa/"><i>FBLN5</i>-related cutis laxa</a> (ARCL1A & ADCL2)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GORAB</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gerodermia osteodysplastica (GO) (OMIM <a href="https://omim.org/entry/231070" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">231070</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>LTBP4</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ltbp4-cutis-laxa/"><i>LTBP4</i>-related cutis laxa</a> (URDS, ARCL1C)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Characterized by severe assoc malformations incl major CHD & severe pulmonary hypertension; diaphragmatic hernia & multiple bladder diverticulae w/vesicoureteral reflux → life-threatening complications & short life span.</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NBAS</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature, optic nerve atrophy, & Pelger-Huet anomaly (SOPH syndrome) (OMIM <a href="https://omim.org/entry/614800" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614800</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hepatopathy; optic atrophy; hypogammaglobulinemia</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PTDSS1</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lenz-Majewski syndrome hyperostotic dwarfism (LMS) (OMIM <a href="https://www.omim.org/entry/151050" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">151050</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early cutis laxa followed by progressive thinning of skin w/prominent veins; severe brachydactyly & unique facial appearance w/prominent eyes distinguish LMS in early stages from other forms of cutis laxa. <sup>2</sup></td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PYCR1</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">De Barsy syndrome B (ARCL3B) (OMIM <a href="https://www.omim.org/entry/614438" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614438</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID (variable); translucent skin; movement disorder</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">ARCL2B <a href="https://www.omim.org/entry/612940" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">612940</a></td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ID (variable); translucent skin</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>RIN2</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">RIN2-related cutis laxa (MACS syndrome) (OMIM <a href="https://www.omim.org/entry/613075" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613075</a>)</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">±</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Very characteristic facial gestalt <sup>3</sup>; cutis laxa is mild & mostly manifests as redundant facial skin.</td></tr><tr><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SLC2A10</i>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/arterial-t/">Arterial tortuosity syndrome</a>
|
||
</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">–</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_4 hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_cutis-laxa.T.disorders_to_consider_in_th_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Individuals may display droopy facial appearance similar to that observed in other forms of cutis laxa <sup>4</sup> & have a high palate w/dental crowding.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADCL = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> cutis laxa; ARCL = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> cutis laxa; CDG = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> disorder of glycosylation; CHD = congenital heart disease; DD = developmental delay; ID = intellectual disability; MACS = <i>m</i>acrocephaly, <i>a</i>lopecia, <i>c</i>utis laxa, & <i>s</i>coliosis; 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="cutis-laxa.TF.3.1"><p class="no_margin">
|
||
<a class="bk_pop" href="#cutis-laxa.REF.adamo.2022.2230">Adamo et al [2022]</a>
|
||
</p></div></dd><dt>2. </dt><dd><div id="cutis-laxa.TF.3.2"><p class="no_margin"><a class="bk_pop" href="#cutis-laxa.REF.sousa.2014.70">Sousa et al [2014]</a>, <a class="bk_pop" href="#cutis-laxa.REF.piard.2018.668">Piard et al [2018]</a></p></div></dd><dt>3. </dt><dd><div id="cutis-laxa.TF.3.3"><p class="no_margin">
|
||
<a class="bk_pop" href="#cutis-laxa.REF.baselvanagaite.2009.254">Basel-Vanagaite et al [2009]</a>
|
||
</p></div></dd><dt>4. </dt><dd><div id="cutis-laxa.TF.3.4"><p class="no_margin"><a class="bk_pop" href="#cutis-laxa.REF.callewaert.2008.150">Callewaert et al [2008]</a>, <a class="bk_pop" href="#cutis-laxa.REF.beyens.2019a.1894">Beyens et al [2019a]</a></p></div></dd></dl></div></div></div></div><div id="cutis-laxa.Management"><h2 id="_cutis-laxa_Management_">Management</h2><div id="cutis-laxa.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>ATP6V0A2</i>-related cutis laxa, the evaluations summarized in <a href="/books/NBK5200/table/cutis-laxa.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobcutislaxaTrecommendedevaluationsfol">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="cutis-laxa.T.recommended_evaluations_fol" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>ATP6V0A2</i>-Related Cutis Laxa</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.recommended_evaluations_fol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.recommended_evaluations_fol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Congenital hip</b>
|
||
<br />
|
||
<b>dislocation</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>For newborns: clinical exam w/hip ultrasound as needed</div></li><li class="half_rhythm"><div>For older child at diagnosis: pelvic x-ray (1x only) to identify hip dysplasia in the event that hip dislocation was not treated properly</div></li></ul>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Inguinal hernia(s)</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical eval</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac valvular</b>
|
||
<br />
|
||
<b>dysplasia</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>High myopia &</b>
|
||
<br />
|
||
<b>other ophthalmic</b>
|
||
<br />
|
||
<b>abnormality</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam, incl refraction (for myopia), slit-lamp exam, fundus exam</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Slit-lamp exam allows diagnosis of corneal dysplasia (seen in 1 person).</td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD/ID / Neurologic</b>
|
||
<br />
|
||
<b>abnormality</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Baseline neurodevelopmental eval</div></li><li class="half_rhythm"><div>Brain MRI</div></li><li class="half_rhythm"><div>EEG if seizures are suspected</div></li></ul>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Coagulation factor</b>
|
||
<br />
|
||
<b>deficiencies</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Full screening, incl von Willebrand factor [<a class="bk_pop" href="#cutis-laxa.REF.beyens.2019b.1142">Beyens et al 2019b</a>]</td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_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_cutis-laxa.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>ATP6V0A2</i>-related cutis laxa to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_evaluations_fol_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_cutis-laxa.T.recommended_evaluations_fol_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="#cutis-laxa.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_cutis-laxa.T.recommended_evaluations_fol_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">DD = developmental delay; ID = intellectual disability; 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="cutis-laxa.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, or certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="cutis-laxa.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="cutis-laxa.T.treatment_of_manifestations" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>ATP6V0A2</i>-Related Cutis Laxa</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.treatment_of_manifestations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.treatment_of_manifestations_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Congenital hip dislocation</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment as recommended by orthopedist</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Inguinal hernia(s)</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>High myopia</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by ophthalmologist</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD/ID</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#cutis-laxa.Developmental_Delay__Intellec">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizure disorder</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td></tr><tr><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Self-image difficulties related to cutis laxa</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Psychological help as needed</td><td headers="hd_h_cutis-laxa.T.treatment_of_manifestations_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">ASM = anti-seizure medication; DD = developmental delay; ID = intellectual disability</p></div></dd><dt>1. </dt><dd><div id="cutis-laxa.TF.5.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div><div id="cutis-laxa.Developmental_Delay__Intellec"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="cutis-laxa.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li><li class="half_rhythm"><div>For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox<sup>®</sup>, anti-parkinsonian medications, or orthopedic procedures.</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p></div><div id="cutis-laxa.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.</p></div></div><div id="cutis-laxa.Surveillance"><h3>Surveillance</h3><div id="cutis-laxa.T.recommended_surveillance_fo" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>ATP6V0A2</i>-Related Cutis Laxa</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.T.recommended_surveillance_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.T.recommended_surveillance_fo_lrgtbl__"><table><thead><tr><th id="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>High myopia & other ophthalmic issues</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam, incl refraction for evidence of progressive myopia & fundus exam to inspect Bruch's membrane</td><td headers="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_cutis-laxa.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">EEG; monitoring of anticonvulsive drug levels</td></tr></tbody></table></div></div></div><div id="cutis-laxa.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to test older and younger sibs for presence of the <i>ATP6V0A2</i> pathogenic variants found in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> in order to identify as early as possible those who would benefit from institution of treatment and preventive measures.</p><p>See <a href="#cutis-laxa.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing 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="cutis-laxa.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="cutis-laxa.Genetic_Counseling"><h2 id="_cutis-laxa_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="cutis-laxa.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>ATP6V0A2</i>-related cutis laxa is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="cutis-laxa.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., presumed to be carriers of one <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing of the parents is recommended to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment. (In rare families, only one parent of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> disorder is heterozygous and the proband is affected as the result of either: (1) one pathogenic variant inherited from the heterozygous parent and a second pathogenic variant that occurred <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> in the proband; or (2) <a class="def" href="/books/n/gene/glossary/def-item/uniparental-isodisomy/">uniparental isodisomy</a> and consequent homozygosity for the pathogenic variant transmitted by a heterozygous parent [<a class="bk_pop" href="#cutis-laxa.REF.j_nsson.2017.519">Jónsson et al 2017</a>].)</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Because cognitive development and possible regression depends on the onset, type, and severity of seizures, considerable <a class="def" href="/books/n/gene/glossary/def-item/intrafamilial-variability/">intrafamilial variability</a> is observed.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The offspring of an individual with <i>ATP6V0A2</i>-related cutis laxa are obligate heterozygotes (carriers) for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ATP6V0A2</i>.</div></li><li class="half_rhythm"><div>To date, individuals with <i>ATP6V0A2</i>-related cutis laxa who have brain malformation are not known to reproduce.</div></li></ul><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of an <i>ATP6V0A2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="cutis-laxa.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ATP6V0A2</i> pathogenic variants in the family.</p></div><div id="cutis-laxa.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#cutis-laxa.Evaluation_of_Relatives_at_Ri">Evaluation of Relatives at Risk</a> for information on evaluating at-risk 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 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="cutis-laxa.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ATP6V0A2</i> pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> for <i>ATP6V0A2-</i>related cutis laxa are possible.</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="cutis-laxa.Resources"><h2 id="_cutis-laxa_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>DermNet NZ</b>
|
||
</div><div>New Zealand</div><div>
|
||
<a href="http://dermnetnz.org/dermal-infiltrative/cutis-laxa.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cutis Laxa</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/cutis-laxa/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cutis laxa</a>
|
||
</div></li></ul>
|
||
</div><div id="cutis-laxa.Molecular_Genetics"><h2 id="_cutis-laxa_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="cutis-laxa.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>ATP6V0A2-Related Cutis Laxa: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5200/table/cutis-laxa.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cutis-laxa.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cutis-laxa.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/23545" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>ATP6V0A2</i>
|
||
</a>
|
||
</td><td headers="hd_b_cutis-laxa.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=23545" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12q24<wbr style="display:inline-block"></wbr>.31</a>
|
||
</td><td headers="hd_b_cutis-laxa.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q9Y487" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">V-type proton ATPase 116 kDa subunit a 2</a>
|
||
</td><td headers="hd_b_cutis-laxa.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/ATP6V0A2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATP6V0A2 database</a>
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</td><td headers="hd_b_cutis-laxa.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=ATP6V0A2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATP6V0A2</a>
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||
</td><td headers="hd_b_cutis-laxa.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ATP6V0A2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATP6V0A2</a>
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</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="cutis-laxa.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
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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||
<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
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="cutis-laxa.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for ATP6V0A2-Related Cutis Laxa (<a href="/omim/219200,278250,611716" 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/NBK5200/table/cutis-laxa.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cutis-laxa.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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||
<a href="/omim/219200" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">219200</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA; ARCL2A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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||
<a href="/omim/278250" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278250</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">WRINKLY SKIN SYNDROME; WSS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/611716" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611716</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ATPase, H+ TRANSPORTING, LYSOSOMAL, V0 SUBUNIT A2; ATP6V0A2</td></tr></tbody></table></div></div><div id="cutis-laxa.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ATP6V0A2</i> encodes the alpha-2 subunit of the v-ATPase complex, which mainly resides in the trans Golgi compartment and adjacent endosomal vesicles. The subunit anchors the complex in the membrane and is part of the channel for proton transport. Loss of this subunit likely perturbs pH regulation and ion homeostasis in Golgi cisternae and vesicles and, possibly through loss of interaction with additional proteins involved in vesicular function, impairs vesicular transport. This leads to impaired posttranslational modification through malpositioning and malfunction of glycosylation enzymes, but also affects secretion, endocytosis, and lysosomal function. The <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of <i>ATP6V0A2</i>-related cutis laxa is partially of developmental origin, but the neurologic decline seen in many individuals also hints at a progressive neuronal disease mechanism.</p><p><b>Mechanism of disease causation.</b>
|
||
<i>ATP6V0A2</i>-related cutis laxa is thought to occur via a <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> mechanism.</p></div></div><div id="cutis-laxa.Chapter_Notes"><h2 id="_cutis-laxa_Chapter_Notes_">Chapter Notes</h2><div id="cutis-laxa.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the families for their continuing participation.</p></div><div id="cutis-laxa.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>16 March 2023 (aa) Revision: <i>EMILIN1</i> added to <a href="#cutis-laxa.Differential_Diagnosis">Differential Diagnosis</a></div></li><li class="half_rhythm"><div>28 January 2021 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>12 February 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>10 May 2011 (cd) Revision: <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> available clinically; <i>ALDH18A1-</i>related cutis laxa added to differential diagnosis</div></li><li class="half_rhythm"><div>23 September 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>19 March 2009 (me) Review posted live</div></li><li class="half_rhythm"><div>10 September 2008 (lvm) Original submission</div></li></ul></div></div><div id="cutis-laxa.References"><h2 id="_cutis-laxa_References_">References</h2><div id="cutis-laxa.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.adamo.2022.2230">Adamo CS, Beyens A, Schiavinato A, Keene DR, Tufa SF, Mörgelin M, Brinckmann J, Sasaki T, Niehoff A, Dreiner M, Pottie L, Muiño-Mosquera L, Gulec EY, Gezdirici A, Braghetta P, Bonaldo P, Wagener R, Paulsson M, Bornaun H, De Rycke R, De Bruyne M, Baeke F, Devine WP, Gangaram B, Tam A, Balasubramanian M, Ellard S, Moore S, Symoens S, Shen J, Cole S, Schwarze U, Holmes KW, Hayflick SJ, Wiszniewski W, Nampoothiri S, Davis EC, Sakai LY, Sengle G, Callewaert B. EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis. <span><span class="ref-journal">Am J Hum Genet. </span>2022;<span class="ref-vol">109</span>:2230–52.</span> [<a href="/pmc/articles/PMC9748297/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9748297</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36351433" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36351433</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.algazali.2001.213">Al-Gazali LI, Sztriha L, Skaff F, Haas D. Gerodermia osteodysplastica and wrinkly skin syndrome: are they the same? <span><span class="ref-journal">Am J Med Genet. </span>2001;<span class="ref-vol">101</span>:213–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11424136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11424136</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.baselvanagaite.2009.254">Basel-Vanagaite L, Sarig O, Hershkovitz D, Fuchs-Telem D, Rapaport D, Gat A, Isman G, Shirazi I, Shohat M, Enk CD, Birk E, Kohlhase J, Matysiak-Scholze U, Maya I, Knopf C, Peffekoven A, Hennies HC, Bergman R, Horowitz M, Ishida-Yamamoto A, Sprecher E. RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2009;<span class="ref-vol">85</span>:254–63.</span> [<a href="/pmc/articles/PMC2725231/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2725231</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19631308" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19631308</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.beyens.2019a.1894">Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, Bostan O, Boute O, Busa T, Canham N, Cil E, Coucke PJ, Cousin MA, Dasouki M, De Backer J, De Paepe A, De Schepper S, De Silva D, Devriendt K, De Wandele I, Deyle DR, Dietz H, Dupuis-Girod S, Fontenot E, Fischer-Zirnsak B, Gezdirici A, Ghoumid J, Giuliano F, Baena N, Haider MZ, Hardin JS, Jeunemaitre X, Klee EW, Kornak U, Landecho MF, Legrand A, Loeys B, Lyonnet S, Michael H, Moceri P, Mohammed S, Muiño-Mosquera L, Nampoothiri S, Pichler K, Prescott K, Rajeb A, Ramos-Arroyo M, Rossi M, Salih M, Seidahmed MZ, Schaefer E, Steichen-Gersdorf E, Temel S, Uysal F, Vanhomwegen M, Van Laer L, Van Maldergem L, Warner D, Willaert A, Collins Ii TR, Taylor A, Davis EC, Zarate Y, Callewaert B. Correction: Arterial tortuosity syndrome: 40 new families and literature review. <span><span class="ref-journal">Genet Med. </span>2019a;<span class="ref-vol">21</span>:1894–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30201961" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30201961</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.beyens.2019b.1142">Beyens A, Moreno-Artero E, Bodemer C, Cox E, Gezdirici A, Yilmaz-Gulec E, Kahloul N, Khau-Van-Kien P, Ogur G, Vasse M, Sahli A, Symoens S, Hadj-Rabia S, Callewaert B. ATP6V0A2-related cutis laxa in 10 new patients: focus on clinical variability and expansion of the phenotype. <span><span class="ref-journal">Exp Dermatol. </span>2019b;<span class="ref-vol">28</span>:1142–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29952037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29952037</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.callewaert.2008.150">Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, Ramos-Arroyo MA, Doco-Fenzy M, Hennekam RC, Pyeritz RE, Krogmann ON, Gillessen-kaesbach G, Wakeling EL, Nik-zainal S, Francannet C, Mauran P, Booth C, Barrow M, Dekens R, Loeys BL, Coucke PJ, De Paepe AM. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. <span><span class="ref-journal">Hum Mutat. </span>2008;<span class="ref-vol">29</span>:150–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17935213" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17935213</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.gardeitchik.2014.888">Gardeitchik T, Mohamed M, Fischer B, Lammens M, Lefeber D, Lace B, Parker M, Ki-Joong Kim K-J, Lim BC, Haberle M, Garavelli L, Jagadeesh S, Kariminejad A, Guerra D, Leao M, Keski-Filppula R, Brunner H, Nijtmans L, van den Heuvel B, Wevers R, Kornak U, Morava E. Clinical and biochemical features guiding the diagnostics in neurometabolic cutis laxa. <span><span class="ref-journal">Eur J Hum Genet. </span>2014;<span class="ref-vol">22</span>:888–95.</span> [<a href="/pmc/articles/PMC4060105/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4060105</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23963297" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23963297</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.greally.2014.1245">Greally MT, Kalis NN, Agab W, Ardati K, Giurgea S, Kornak U, Van Maldergem L. Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: report of three patients. <span><span class="ref-journal">Am J Med Genet A. </span>2014;<span class="ref-vol">164A</span>:1245–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24478233" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24478233</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.guillard.2009.903">Guillard M, Dimopoulou A, Fischer B, Morava E, Lefeber DJ, Kornak U, Wevers RA. Vacuolar H+-ATPase meets glycosylation in patients with cutis laxa. <span><span class="ref-journal">Biochim Biophys Acta. </span>2009;<span class="ref-vol">1792</span>:903–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19171192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19171192</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.hucthagowder.2009.2149">Hucthagowder V, Morava E, Kornak U, Lefeber DJ, Fischer B, Dimopoulou A, Aldinger A, Choi J, Davis EC, Abuelo DN, Adamowicz M, Al-Aama J, Basel-Vanagaite L, Fernandez B, Greally MT, Gillessen-Kaesbach G, Kayserili H, Lemyre E, Tekin M, Türkmen S, Tuysuz B, Yüksel-Konuk B, Mundlos S, Van Maldergem L, Wevers RA, Urban Z. Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival. <span><span class="ref-journal">Hum Mol Genet. </span>2009;<span class="ref-vol">18</span>:2149–65.</span> [<a href="/pmc/articles/PMC2685755/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2685755</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19321599" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19321599</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.jones.2013.78">Jones MA, Rhodenizer D, da Silva C, Huff IJ, Keong L, Bean LJ, Coffee B, Collins C, Tanner AK, He M, Hegde MR. Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing. <span><span class="ref-journal">Mol Genet Metab. </span>2013;<span class="ref-vol">110</span>:78–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23806237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23806237</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.j_nsson.2017.519">Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.morava.2008.28">Morava E, Lefeber DJ, Urban Z, de Meirleir L, Meinecke P, Gillessen Kaesbach G, Sykut-Cegielska J, Adamowicz M, Salafsky I, Ranells J, Lemyre E, van Reeuwijk J, Brunner HG, Wevers RA. Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. <span><span class="ref-journal">Eur J Hum Genet. </span>2008;<span class="ref-vol">16</span>:28–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17971833" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17971833</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.morava.2005.414">Morava E, Wopereis S, Coucke P, Gillessen-Kaesbach G, Voit T, Smeitink J, Wevers R, Grünewald S. Defective protein glycosylation in patients with cutis laxa syndrome. <span><span class="ref-journal">Eur J Hum Genet. </span>2005;<span class="ref-vol">13</span>:414–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15657616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15657616</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.morlino.2021.955">Morlino S, Nardella G, Castellana S, Micale L, Copetti M, Fusco C, Castori M. Review of clinical and molecular variability in autosomal recessive cutis laxa 2A. <span><span class="ref-journal">Am J Med Genet. </span>2021;<span class="ref-vol">185</span>:955–65.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33369135" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33369135</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.piard.2018.668">Piard J, Lespinasse J, Vlckova M, Mensah MA, Iurian S, Simandlova M, Malikova M, Bartsch O, Rossi M, Lenoir M, Nugues F, Mundlos S, Kornak U, Stanier P, Sousa SB, Van Maldergem L. Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1. <span><span class="ref-journal">Am J Med Genet. </span>2018;<span class="ref-vol">176</span>:668–75.</span> [<a href="/pmc/articles/PMC5838527/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5838527</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29341480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29341480</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.sousa.2014.70">Sousa SB, Jenkins D, Chanudet E, Tasseva G, Ishida M, Anderson G, Stanier P, Ryten M, Sa J, Saraiva JM, Barnicoat A, Scott R, Calder A, Wattanasirichaigoon D, Chrzanowska K, Simandlová M, Van Maldergem L, Beales PL, Vance JE, Moore GE. Gain-of-function mutations in the Phosphatidylserine Synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. <span><span class="ref-journal">Nat Genet. </span>2014;<span class="ref-vol">46</span>:70–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24241535" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24241535</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.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="cutis-laxa.REF.van_maldergem.2008.1602">Van Maldergem L, Yuksel-Apak M, Kayserili H, Seemanova E, Giurgea S, Basel-Vanagaite L, Leao-Teles E, Vigneron J, Foulon M, Greally M, Jaeken J, Mundlos S, Dobyns WB. Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debré-type. <span><span class="ref-journal">Neurology. </span>2008;<span class="ref-vol">71</span>:1602–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18716235" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18716235</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cutis-laxa.REF.wopereis.2005.156">Wopereis S, Morava E, Grünewald S, Mills PB, Winchester BG, Clayton P, Coucke P, Huijben KM, Wevers RA. A combined defect in the biosynthesis of N- and O-glycans in patients with cutis laxa and neurological involvement: the biochemical characteristics. <span><span class="ref-journal">Biochim Biophys Acta. </span>2005;<span class="ref-vol">1741</span>:156–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15955459" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15955459</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/NBK5200/?report=reader">PubReader</a></li><li><a href="/books/NBK5200/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK5200" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK5200" style="display:none" title="Cite this Page"><div class="bk_tt">Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. 2009 Mar 19 [Updated 2023 Mar 16]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK5200/pdf/Bookshelf_NBK5200.pdf">PDF version of this page</a> (514K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" 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="#cutis-laxa.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#cutis-laxa.GeneReview_Scope" ref="log$=inpage&link_id=inpage"><i>GeneReview</i> Scope</a></li><li><a href="#cutis-laxa.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#cutis-laxa.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#cutis-laxa.Genetically_Related_Allelic_D" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#cutis-laxa.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#cutis-laxa.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#cutis-laxa.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#cutis-laxa.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#cutis-laxa.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#cutis-laxa.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#cutis-laxa.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" 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/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" 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>
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id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301599" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Beta-Thalassemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Beta-Thalassemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Langer AL. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a 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ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Von Willebrand Disease.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Von Willebrand Disease.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Johnsen J. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=20301755" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See 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href="/portal/utils/pageresolver.fcgi?recordid=67d2cecf67c23b31e0ab8d78">ATP6V0A2-Related Cutis Laxa - GeneReviews®</a><div class="ralinkpop offscreen_noflow">ATP6V0A2-Related Cutis Laxa - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d2cece84f3725e592c0787">Table B. 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[OMIM Entries for ATP6V0A2-Related Cutis Laxa (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d2ceadcde49f3df7c0dc8c">RecName: Full=V-type proton ATPase 116 kDa subunit a 2; Short=V-ATPase 116 kDa s...</a><div class="ralinkpop offscreen_noflow">RecName: Full=V-type proton ATPase 116 kDa subunit a 2; Short=V-ATPase 116 kDa subunit a 2; AltName: Full=Lysosomal H(+)-transporting ATPase V0 subunit a 2; AltName: Full=TJ6; AltName: Full=Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2<div class="brieflinkpopdesc">gi|172046607|sp|Q9Y487.2|VPP2_HUMAN</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d2ce9dcde49f3df7c06a4f">Wrinkly skin syndrome</a><div class="ralinkpop offscreen_noflow">Wrinkly skin syndrome<div class="brieflinkpopdesc"></div></div><div class="tertiary">MedGen</div></li><li class="ra_qry two_line"><a class="htb" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d2ce9c84f3725e592a9c93">C0406587[conceptid] <span class="number">(1)</span></a><div class="tertiary">MedGen</div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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