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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="X-Linked Spondyloepiphyseal Dysplasia Tarda" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/04/06" /><meta name="citation_author" content="George E Tiller" /><meta name="citation_pmid" content="20301324" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1145/" /><meta name="citation_keywords" content="TRAPPC2-Related X-Linked Spondyloepiphyseal Dysplasia Tarda" /><meta name="citation_keywords" content="TRAPPC2-Related X-Linked Spondyloepiphyseal Dysplasia Tarda" /><meta name="citation_keywords" content="Trafficking protein particle complex subunit 2" /><meta name="citation_keywords" content="TRAPPC2" /><meta name="citation_keywords" content="X-Linked Spondyloepiphyseal Dysplasia Tarda" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="X-Linked Spondyloepiphyseal Dysplasia Tarda" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="George E Tiller" /><meta name="DC.Date" content="2023/04/06" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1145/" /><meta name="description" content="In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around age six to eight years. Final adult height is typically 137-163 cm. Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved but to a variable degree. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared. Motor and cognitive milestones are normal." /><meta name="og:title" content="X-Linked Spondyloepiphyseal Dysplasia Tarda" /><meta name="og:type" content="book" /><meta name="og:description" content="In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. 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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="#__NBK1145_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1145_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/sider-anemia/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/xp/" 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="_NBK1145_"><span class="title" itemprop="name">X-Linked Spondyloepiphyseal Dysplasia Tarda</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>TRAPPC2</i>-Related X-Linked Spondyloepiphyseal Dysplasia Tarda</div><p class="contrib-group"><span itemprop="author">George E Tiller</span>, MD, PhD.</p><a data-jig="ncbitoggler" href="#__NBK1145_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1145_ai__"><div class="contrib half_rhythm"><span itemprop="author">George E Tiller</span>, MD, PhD<div class="affiliation small">Department of Genetics
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Southern California Permanente Medical Group
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Los Angeles, California<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.pk@rellit.e.egroeg" class="oemail">gro.pk@rellit.e.egroeg</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">November 1, 2001</span>; Last Revision: <span itemprop="dateModified">April 6, 2023</span>.</p><p><em>Estimated reading time: 15 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="sedt.Summary" itemprop="description"><h2 id="_sedt_Summary_">Summary</h2><div><h4 class="inline">Clinical description.</h4><p>In adults, <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around age six to eight years. Final adult height is typically 137-163 cm. Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved but to a variable degree. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared. Motor and cognitive milestones are normal.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The clinical diagnosis of <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT can be established in a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic radiographic findings (which typically appear prior to puberty) including: multiple epiphyseal abnormalities, platyspondyly with characteristic superior and inferior "humping" seen on lateral view, scoliosis, hypoplastic odontoid process, short femoral necks, and coxa vara; evidence of premature osteoarthritis appears in young adulthood. The molecular diagnosis of X-linked SEDT can be established in a male proband with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>TRAPPC2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. The molecular diagnosis of X-linked SEDT can be established in a female proband with osteoarthritis and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic variant in <i>TRAPPC2</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment for scoliosis and kyphoscoliosis per orthopedic surgeon; surgical intervention may include spine surgery (correction of scoliosis or kyphosis). Pain management as needed for osteoarthritis; joint replacement (hip, knee, shoulder) as needed.</p><p><i>Surveillance</i>: Cervical spine films prior to school age and before any surgical procedure involving general anesthesia to assess for clinically significant odontoid hypoplasia. Annual follow up for assessment scoliosis and joint pain.</p><p><i>Agents/circumstances to avoid:</i> Extreme neck flexion and extension in individuals with odontoid hypoplasia. Activities and occupations that place undue stress on the spine and weight-bearing joints.</p><p><i>Evaluation of relatives at risk:</i> Presymptomatic testing in males at risk may obviate unnecessary diagnostic testing for other causes of short stature and/or osteoarthritis.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>By definition, <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT is inherited in an X-linked manner. When performed, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> of all mothers of affected sons determined that regardless of family history all were carriers of a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>TRAPPC2</i>. Carrier females are at a 50% risk of transmitting the <i>TRAPPC2</i> pathogenic variant in each pregnancy: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will not be affected. None of the sons of an affected male will be affected; all daughters will be carriers of the <i>TRAPPC2</i> pathogenic variant. Carrier testing of at-risk female relatives and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for pregnancies at increased risk are possible if the pathogenic variant in the family has been identified.</p></div></div><div id="sedt.Diagnosis"><h2 id="_sedt_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda have been published.</p><div id="sedt.Suggestive_Findings"><h3>Suggestive Findings</h3><p><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT) <b>should be suspected</b> in males with the following findings:</p><ul><li class="half_rhythm"><div>Disproportionate short stature in adolescence or adulthood and a relatively short trunk and barrel-shaped chest. Upper- to lower-body segment ratio is usually about 0.8. Arm span typically exceeds height by 10-20 cm. Short neck, dorsal kyphosis, and lumbar hyperlordosis may be evident by puberty.</div></li><li class="half_rhythm"><div>Early-onset osteoarthritis, especially in the hip joints</div></li><li class="half_rhythm"><div>A family history consistent with <a class="def" href="/books/n/gene/glossary/def-item/x-linked-recessive/">X-linked recessive</a> inheritance. A positive family history is contributory but not necessary.</div></li><li class="half_rhythm"><div>Absence of cleft palate and retinal detachment (frequently present in SED congenita; see <a href="#sedt.Differential_Diagnosis">Differential Diagnosis</a>)</div></li></ul></div><div id="sedt.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The clinical diagnosis of <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT <b>can be established</b> in a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic radiographic findings, or the molecular diagnosis can be established in a male proband with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>TRAPPC2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1145/table/sedt.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobsedtTmoleculargenetictestingusedin">Table 1</a>) if radiographic findings are inconclusive.</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="#sedt.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 <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>TRAPPC2</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis.</p><div id="sedt.Radiographic_Findings"><h4>Radiographic Findings</h4><p>The following radiographic findings may not be manifest in an affected male in early childhood and typically appear prior to puberty (<a class="figpopup" href="/books/NBK1145/figure/sedt.F1/?report=objectonly" target="object" rid-figpopup="figsedtF1" rid-ob="figobsedtF1">Figure 1</a>):</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figsedtF1" co-legend-rid="figlgndsedtF1"><a href="/books/NBK1145/figure/sedt.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figsedtF1" rid-ob="figobsedtF1"><img class="small-thumb" src="/books/NBK1145/bin/sedt-Image001.gif" src-large="/books/NBK1145/bin/sedt-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndsedtF1"><h4 id="sedt.F1"><a href="/books/NBK1145/figure/sedt.F1/?report=objectonly" target="object" rid-ob="figobsedtF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Radiographs of a male age 31 years with SEDT A. Platyspondyly with superior and inferior humping of vertebral bodies</p></div></div><ul><li class="half_rhythm"><div>Multiple epiphyseal abnormalities</div></li><li class="half_rhythm"><div>Platyspondyly (flattened vertebral bodies) with characteristic superior and inferior "humping" seen on lateral view; narrow disc spaces in adulthood</div></li><li class="half_rhythm"><div>Scoliosis / kyphoscoliosis</div></li><li class="half_rhythm"><div>Hypoplastic odontoid process</div></li><li class="half_rhythm"><div>Short femoral necks</div></li><li class="half_rhythm"><div>Coxa vara</div></li><li class="half_rhythm"><div>Evidence of premature osteoarthritis beginning in young adulthood</div></li></ul><p>Radiographs of symptomatic males should be reviewed by a radiologist experienced with bone dysplasias.</p></div><div id="sedt.Molecular_Genetic_Testing"><h4>Molecular Genetic Testing</h4><p>Testing approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> and a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>TRAPPC2</i> is performed first to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>TRAPPC2</i> and other genes of interest (see <a href="#sedt.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered. This method may be especially useful if expert radiographic interpretation is not available. 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>; thus, clinicians need to determine which multigene panel 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>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><div id="sedt.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> Spondyloepiphyseal Dysplasia Tarda</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sedt.T.molecular_genetic_testing_used_in_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_sedt.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_sedt.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TRAPPC2</i>
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</td><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_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_sedt.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">84% <sup>4</sup></td></tr><tr><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_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_sedt.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16% <sup>6</sup></td></tr><tr><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>7</sup></td><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_sedt.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="sedt.TF.1.1"><p class="no_margin">See <a href="/books/NBK1145/#sedt.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="sedt.TF.1.2"><p class="no_margin">See <a href="#sedt.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="sedt.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="sedt.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="#sedt.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="sedt.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="sedt.TF.1.6"><p class="no_margin">Males initially suspected on <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> of having a <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in whom the deletion is subsequently confirmed by <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a></p></div></dd><dt>7. </dt><dd><div id="sedt.TF.1.7"><p class="no_margin">It is unknown whether negative molecular analysis reflects <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> heterogeneity or clinical misdiagnosis.</p></div></dd></dl></div></div></div></div></div></div><div id="sedt.Clinical_Characteristics"><h2 id="_sedt_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sedt.Clinical_Description"><h3>Clinical Description</h3><p><b>Males.</b> At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around grade school (age 6-8 years). Adults with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT) have disproportionately short stature with short trunk and arm span significantly greater than height. Final adult height is typically 137-163 cm [<a class="bk_pop" href="#sedt.REF.whyte.1999.9">Whyte et al 1999</a>, <a class="bk_pop" href="#sedt.REF.jones.2013">Jones et al 2013</a>, <a class="bk_pop" href="#sedt.REF.rimoin.2013">Rimoin et al 2013</a>].</p><p><b>Scoliosis/kyphoscoliosis</b> and <b>odontoid hypoplasia</b> are known radiographic features. Data on the incidence, onset, and severity of these features have not been published.</p><p><b>Osteoarthritis.</b> Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved to variable degrees. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared.</p><p>Affected males achieve normal motor and cognitive milestones. Life span and intelligence appear normal.</p><p><b>Heterozygous females.</b> Carrier females typically show no phenotypic changes, but mild symptoms of osteoarthritis have been reported [<a class="bk_pop" href="#sedt.REF.whyte.1999.9">Whyte et al 1999</a>].</p></div><div id="sedt.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Data are inadequate to reliably correlate clinical severity to a specific <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. All pathogenic variants identified thus far, irrespective of their molecular basis, result in an almost identical <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, including the true <a class="def" href="/books/n/gene/glossary/def-item/null/">null</a> variants.</p></div><div id="sedt.Nomenclature"><h3>Nomenclature</h3><p>Spondyloepiphyseal dysplasia is a general term that describes the radiographic abnormalities seen in several skeletal dysplasias, including <a href="/books/n/gene/psach/">pseudoachondroplasia</a>. The "congenita" form is evident at birth, whereas the "tarda" form is usually evident by school age.</p><p>SED tarda commonly refers to the <a class="def" href="/books/n/gene/glossary/def-item/x-linked-recessive/">X-linked recessive</a> form of the disorder, although rare <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> and <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> "tarda" forms have been described.</p><p>In the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bk_pop" href="#sedt.REF.unger.2023">Unger et al 2023</a>], <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda is referred to as <i>TRAPPC2</i>-related X-linked spondyloepiphyseal dysplasia tarda and included in the spondyloepi(meta)physeal dysplasias group.</p></div><div id="sedt.Prevalence"><h3>Prevalence</h3><p>The prevalence is 1:150,000-1:200,000 [<a class="bk_pop" href="#sedt.REF.wynnedavies.1985.133">Wynne-Davies & Gormley 1985</a>].</p><p>Pathogenic variants in <i>TRAPPC2</i> have been found in several populations including European [<a class="bk_pop" href="#sedt.REF.gedeon.2001.1386">Gedeon et al 2001</a>], Japanese [<a class="bk_pop" href="#sedt.REF.matsui.2001.328">Matsui et al 2001</a>], and Chinese [<a class="bk_pop" href="#sedt.REF.shu.2002.106">Shu et al 2002</a>], an observation suggesting that no specific population is at increased risk.</p></div></div><div id="sedt.Genetically_Related_Allelic_Disorde"><h2 id="_sedt_Genetically_Related_Allelic_Disorde_">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>TRAPPC2.</i></p></div><div id="sedt.Differential_Diagnosis"><h2 id="_sedt_Differential_Diagnosis_">Differential Diagnosis</h2><p><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT) is distinguished from other forms of spondyloepiphyseal dysplasia (SED) by its later onset and X-linked inheritance (see <a href="/books/NBK1145/table/sedt.T.forms_of_spondyloepiphyseal_dyspl/?report=objectonly" target="object" rid-ob="figobsedtTformsofspondyloepiphysealdyspl">Table 2</a>).</p><div id="sedt.T.forms_of_spondyloepiphyseal_dyspl" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Forms of Spondyloepiphyseal Dysplasia of Interest in the Differential Diagnosis of X-Linked Spondyloepiphyseal Dysplasia Tarda</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.forms_of_spondyloepiphyseal_dyspl/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.forms_of_spondyloepiphyseal_dyspl_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of Differential Diagnosis Disorder</th><th id="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Features/<br />Comment</th></tr></thead><tbody><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CCN6</i><br />(<i>WISP3</i>)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ppr-dysp/">Progressive pseudorheumatoid dysplasia</a> (PED)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predominant involvement of articular cartilage w/progressive joint stiffness & enlargement & w/o inflammation. Onset (age ~3-6 yrs) begins w/involvement of interphalangeal joints; later involvement of large joints & spine causes significant joint contractures, gait disturbance, & scoliosis &/or kyphosis, → abnormal posture & significant morbidity. Short stature (<3rd centile) becomes evident in adolescence.</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unlike <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT, joint swelling & hand involvement are common features of PED.</td></tr><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>COL2A1</i>
|
||
</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SED congenita (SEDC) (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD <sup>1</sup></td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usually evident at birth w/disproportionate short stature, short extremities, broad chest, characteristic facies, myopia, & ↑ incidence of cleft palate & hearing loss. Delayed/poor ossification of vertebrae & pubic bones; long bones are short w/hypoplastic epiphyses. ↑ risk for tracheolaryngomalacia & related respiratory complications & retinal detachment. ↑ risk for cervical instability.</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SED congenita is most common form of SED.</td></tr><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Spondyloperipheral dysplasia (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild-to-moderate disproportionate short stature & short extremities, brachydactyly type E, short ulnae, variable clubfeet, cleft palate, myopia, & hearing loss; ovoid vertebra, delayed ossification of pubic bones, & flattened & irregular epiphyses in long bones. Premature hip arthrosis causes joint pain.</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>COL2A1</i>
|
||
<br />
|
||
<i>COL9A1</i>
|
||
<br />
|
||
<i>COL9A2</i>
|
||
<br />
|
||
<i>COL9A3</i>
|
||
<br />
|
||
<i>COL11A1</i>
|
||
<br />
|
||
<i>COL11A2</i>
|
||
</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/stickler/">Stickler syndrome</a>
|
||
</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR <sup>2</sup></td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Connective tissue disorder; can incl high myopia, hearing loss (both conductive & sensorineural); midfacial underdevelopment & cleft palate (either alone or as part of Pierre Robin sequence); & mild SED &/or precocious arthritis.</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>COL9A1</i>
|
||
<br />
|
||
<i>COL9A2</i>
|
||
<br />
|
||
<i>COL9A3</i>
|
||
<br />
|
||
<i>COMP</i>
|
||
<br />
|
||
<i>MATN3</i>
|
||
</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/edm-ad/">Multiple epiphyseal dysplasia, autosomal dominant</a> (MED)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents early in childhood, usually w/pain in hips &/or knees after exercise; affected children complain of fatigue w/long-distance walking; waddling gait may be present. Adult height in lower range of normal or mildly shortened; limbs relatively short compared to trunk; progressive pain & joint deformity → early-onset osteoarthritis esp of large weight-bearing joints.</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By definition, spine in MED is normal, although Schmorl bodies & irregular vertebral end plates may be observed.</td></tr><tr><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GALNS</i>
|
||
<br />
|
||
<i>GLB1</i>
|
||
</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Morquio syndrome (<a href="/books/n/gene/mps4a/">MPS IVA</a> & MPS IVB) (See <a href="/books/n/gene/gm1-ganglio/"><i>GLB1 </i>Disorders</a>.)</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysostosis multiplex, odontoid hypoplasia, short stature, hepatomegaly & cloudy corneas</td><td headers="hd_h_sedt.T.forms_of_spondyloepiphyseal_dyspl_1_1_1_5" 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">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; MPS = mucopolysaccharidosis; SED = spondyloepiphyseal dysplasia; SEDT = spondyloepiphyseal dysplasia tarda</p></div></dd><dt>1. </dt><dd><div id="sedt.TF.2.1"><p class="no_margin">Rare instances of <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance in SEDC have been reported (see <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>).</p></div></dd><dt>2. </dt><dd><div id="sedt.TF.2.2"><p class="no_margin">Stickler syndrome caused by pathogenic variants in <i>COL2A1</i>, <i>COL11A1</i>, or <i>COL11A2</i> is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner; Stickler syndrome caused by pathogenic variants in <i>COL9A1</i>, <i>COL9A2</i>, or <i>COL9A3</i> is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div></dd></dl></div></div></div><p>
|
||
<b>Other</b>
|
||
</p><ul><li class="half_rhythm"><div><b>SED tarda,</b>
|
||
<b><a class="def" href="/books/n/gene/glossary/def-item/autosomal/">autosomal</a> forms</b> (rare). A dominant form (OMIM <a href="https://omim.org/entry/184100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">184100</a>) may be caused by pathogenic variants in <i>COL2A1</i>; a recessive form has been described clinically but not molecularly defined.</div></li><li class="half_rhythm"><div><b>Scheuermann disease</b> (OMIM <a href="https://omim.org/entry/181440" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">181440</a>) is a term applied to premature osteoarthritis of the spine regardless of etiology.</div></li></ul></div><div id="sedt.Management"><h2 id="_sedt_Management_">Management</h2><div id="sedt.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT), the evaluations summarized in <a href="/books/NBK1145/table/sedt.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobsedtTrecommendedevaluationsfollowing">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended:</p><div id="sedt.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> Spondyloepiphyseal Dysplasia Tarda</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sedt.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sedt.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sedt.T.recommended_evaluations_following_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_sedt.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeleton</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete radiographic survey to incl scoliosis series if clinically indicated</td><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess extent of skeletal manifestations</td></tr><tr><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Flexion-extension radiographs of cervical spine</div></li><li class="half_rhythm"><div>Flexion-extension MRI if instability & compression seen on radiographs or interpretation on radiographs is limited (e.g., in young persons w/delayed ossification in upper cervical spine)</div></li></ul>
|
||
</td><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for clinically significant odontoid hypoplasia</td></tr><tr><td headers="hd_h_sedt.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_evaluations_following_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_sedt.T.recommended_evaluations_following_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 SEDT to facilitate medical & personal decision making</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">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="sedt.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="sedt.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="sedt.T.treatment_of_manifestations_in_in" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> Spondyloepiphyseal Dysplasia Tarda</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.treatment_of_manifestations_in_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.treatment_of_manifestations_in_in_lrgtbl__"><table><thead><tr><th id="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/<br />Other</th></tr></thead><tbody><tr><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Odontoid</b>
|
||
<br />
|
||
<b>hypoplasia</b>
|
||
</td><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Precautions during intubation/surgery to avoid hyperextension</td><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Obtain cervical spinal films prior to any surgical procedure involving general anesthesia to assess for clinically significant odontoid hypoplasia.</td></tr><tr><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Scoliosis/</b>
|
||
<br />
|
||
<b>Kyphoscoliosis</b>
|
||
</td><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Treatment per orthopedic surgeon</div></li><li class="half_rhythm"><div>Spine surgery (correction of scoliosis or kyphosis) may be indicated.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Osteoarthritis</b>
|
||
</td><td headers="hd_h_sedt.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Chronic pain management</div></li><li class="half_rhythm"><div>Surgical intervention may incl joint replacement (hip, knee, shoulder).</div></li></ul>
|
||
</td></tr></tbody></table></div></div></div><div id="sedt.Surveillance"><h3>Surveillance</h3><div id="sedt.T.recommended_surveillance_for_indi" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> Spondyloepiphyseal Dysplasia Tarda</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.recommended_surveillance_for_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.recommended_surveillance_for_indi_lrgtbl__"><table><thead><tr><th id="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sedt.T.recommended_surveillance_for_indi_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_sedt.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Odontoid hypoplasia</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Flexion-extension radiographs of cervical spine</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Obtain prior to school age to assess for clinically significant odontoid hypoplasia.</td></tr><tr><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Scoliosis/</b>
|
||
<br />
|
||
<b>Kyphoscoliosis</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical eval w/spine radiographs if clinically indicated</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Osteoarthritis</b>
|
||
</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical eval for osteoarthritis</td><td headers="hd_h_sedt.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr></tbody></table></div></div></div><div id="sedt.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>The following should be avoided:</p><ul><li class="half_rhythm"><div>In individuals with odontoid hypoplasia, extreme neck flexion and extension</div></li><li class="half_rhythm"><div>Activities and occupations that place undue stress on the spine and weight-bearing joints</div></li></ul></div><div id="sedt.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>If the <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the family is known, presymptomatic genetic testing of at-risk males allows early diagnosis and may obviate unnecessary diagnostic testing for other causes of short stature and/or osteoarthritis.</p><p>See <a href="#sedt.Related_Genetic_Counseling_Issues">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="sedt.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="sedt.Genetic_Counseling"><h2 id="_sedt_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="sedt.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>By definition, <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> spondyloepiphyseal dysplasia tarda (X-linked SEDT) is inherited in an X-linked manner.</p></div><div id="sedt.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 class="half_rhythm">The father of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT will not have the disorder nor will he be <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for the causative <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div class="half_rhythm">In a family with more than one affected individual, the mother of an affected male is an obligate <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>. Note: If a woman has more than one affected child and no other affected relatives and if the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in her DNA, she most likely has <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>. Although no instances of maternal germline mosaicism have been reported, it remains a possibility.</div></li><li class="half_rhythm"><div class="half_rhythm">If a male is the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case), the mother may be a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> or the affected male may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, in which case the mother is not a carrier.</div><div class="half_rhythm">In reported individuals for whom <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> was available in a research laboratory, all mothers of affected sons were carriers of a <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> regardless of family history [<a class="bk_pop" href="#sedt.REF.gedeon.2001.1386">Gedeon et al 2001</a>]. Mothers of affected sons who are not carriers have not been reported to date.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs of a male proband with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting the pathogenic variant in each pregnancy is 50%.</div><ul><li class="half_rhythm"><div>Males who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be affected;</div></li><li class="half_rhythm"><div>Females who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be carriers and will usually not be affected (see <a href="#sedt.Clinical_Description">Clinical Description</a>, <b>Heterozygous females</b>).</div></li></ul></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case and if the <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population because of the theoretic possibility of maternal <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p><b>Offspring of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Affected males transmit the <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> to all of their daughters and none of their sons.</p><p><b>Other family members.</b> The maternal aunts and maternal female cousins of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> may be at risk of being carriers and the aunts' offspring, depending on their sex, may be at risk of being carriers or of being affected.</p></div><div id="sedt.Carrier_Detection"><h3>Carrier Detection</h3><p>Identification of female heterozygotes requires either prior identification of the <i>TRAPPC2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the family or, if an affected male is not available for testing, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> first by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, and if no pathogenic variant is identified, by <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>.</p><p>Note: Females who are heterozygotes (carriers) for <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT may develop minimal clinical findings related to the disorder [<a class="bk_pop" href="#sedt.REF.whyte.1999.9">Whyte et al 1999</a>].</p></div><div id="sedt.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#sedt.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of genetic status, and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#sedt.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="sedt.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT-causing <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has 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> 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="sedt.Resources"><h2 id="_sedt_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>Human Growth Foundation</b>
|
||
</div><div>
|
||
<a href="https://www.hgfound.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">hgfound.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Little People of America</b>
|
||
</div><div><b>Phone:</b> 888-LPA-2001; 714-368-3689</div><div><b>Fax:</b> 707-721-1896</div><div><b>Email:</b> info@lpaonline.org</div><div>
|
||
<a href="https://www.lpaonline.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">lpaonline.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MAGIC Foundation</b>
|
||
</div><div><b>Phone:</b> 630-836-8200</div><div><b>Email:</b> contactus@magicfoundation.org</div><div>
|
||
<a href="https://www.magicfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">magicfoundation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>UCLA International Skeletal Dysplasia Registry (ISDR)</b>
|
||
</div><div><b>Phone:</b> 310-825-8998</div><div>
|
||
<a href="https://www.uclahealth.org/ortho/isdr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Skeletal Dysplasia Registry</a>
|
||
</div></li></ul>
|
||
</div><div id="sedt.Molecular_Genetics"><h2 id="_sedt_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="sedt.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>X-Linked Spondyloepiphyseal Dysplasia Tarda: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sedt.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sedt.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sedt.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sedt.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_sedt.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sedt.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sedt.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/6399" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>TRAPPC2</i>
|
||
</a>
|
||
</td><td headers="hd_b_sedt.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=6399" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xp22<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_b_sedt.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P0DI81" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Trafficking protein particle complex subunit 2</a>
|
||
</td><td headers="hd_b_sedt.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/TRAPPC2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TRAPPC2 database</a>
|
||
</td><td headers="hd_b_sedt.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=TRAPPC2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TRAPPC2</a>
|
||
</td><td headers="hd_b_sedt.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TRAPPC2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TRAPPC2</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="sedt.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="sedt.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for X-Linked Spondyloepiphyseal Dysplasia Tarda (<a href="/omim/300202,313400" 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/NBK1145/table/sedt.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/300202" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300202</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TRACKING PROTEIN PARTICLE COMPLEX, SUBUNIT 2; TRAPPC2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/313400" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">313400</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPONDYLOEPIPHYSEAL DYSPLASIA TARDA, X-LINKED; SEDT</td></tr></tbody></table></div></div><div id="sedt.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>TRAPPC2</i> (previously <i>SEDL</i>) encodes the 140-amino acid protein "sedlin," which appears to be ubiquitously expressed [<a class="bk_pop" href="#sedt.REF.gedeon.1999.400">Gedeon et al 1999</a>, <a class="bk_pop" href="#sedt.REF.g_cz.2000.242">Gécz et al 2000</a>]. Sedlin is an essential component of the TRAPP (<i>tra</i>fficking <i>p</i>rotein <i>p</i>article) complex that is required for the export of procollagen trimers (e.g., type II collagen) from the endoplasmic reticulum to the Golgi, which ultimately permits incorporation of these proteins into the extracellular matrix [<a class="bk_pop" href="#sedt.REF.venditti.2012.1668">Venditti et al 2012</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p><p><b><i>TRAPPC2</i>-specific laboratory technical considerations.</b>
|
||
<i>TRAPPC2</i> contains six exons with the translation start site in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 3. The exon and multiexon deletions (see also HGMD in <a href="/books/NBK1145/#sedt.molgen.TA">Table A</a>) would not be detected in <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> females by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> (see <a href="/books/NBK1145/table/sedt.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobsedtTmoleculargenetictestingusedin">Table 1</a>). Sequence analysis should include flanking <a class="def" href="/books/n/gene/glossary/def-item/intronic/">intronic</a> sequences, which is customary to evaluate splice junctions. This is particularly important with <i>TRAPPC2</i>, as there is an expressed <a class="def" href="/books/n/gene/glossary/def-item/pseudogene/">pseudogene</a> which is devoid of introns [<a class="bk_pop" href="#sedt.REF.g_cz.2000.242">Gécz et al 2000</a>].</p><p><b>Notable <i>TRAPPC2</i></b>
|
||
<b>variants.</b> <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> SEDT-causing pathogenic variants in <i>TRAPPC2</i> include <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</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/missense/">missense</a> variants and deletions.</p><div id="sedt.T.notable_recurrent_trappc2_pathoge" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Notable Recurrent <i>TRAPPC2</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1145/table/sedt.T.notable_recurrent_trappc2_pathoge/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sedt.T.notable_recurrent_trappc2_pathoge_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of All Affected<br />Individuals w/Variant</th><th id="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001011658.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001011658<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.93+5G>A</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~18%</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_5" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Reviewed by <a class="bk_pop" href="#sedt.REF.gedeon.2001.1386">Gedeon et al [2001]</a>, <a class="bk_pop" href="#sedt.REF.tiller.2001.1398">Tiller et al [2001]</a>, <a class="bk_pop" href="#sedt.REF.shaw.2003.235">Shaw et al [2003]</a>, & <a class="bk_pop" href="#sedt.REF.fiedler.2004.103">Fiedler et al [2004]</a></td></tr><tr><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001011658.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001011658<wbr style="display:inline-block"></wbr>.3</a>
|
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<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001011658.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001011658<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.157_158delAT</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met53ValfsTer35</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~5%</td></tr><tr><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.191_192delTG</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val64GlyfsTer24</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~4%</td></tr><tr><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.271_275delCAAGA</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln91ArgfsTer9</td><td headers="hd_h_sedt.T.notable_recurrent_trappc2_pathoge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~13%</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the author. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="sedt.Chapter_Notes"><h2 id="_sedt_Chapter_Notes_">Chapter Notes</h2><div id="sedt.Author_History"><h3>Author History</h3><p>George E Tiller, MD, PhD (2001-present)<br />Vickie L Hannig, MS; Vanderbilt University Medical Center (2001-2020)</p></div><div id="sedt.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>6 April 2023 (sw) Revision: "<i>TRAPPC2</i>-Related X-Linked Spondyloepiphyseal Dysplasia Tarda" added as a synonym; Nosology of Genetic Skeletal Disorders: 2023 Revision [<a class="bk_pop" href="#sedt.REF.unger.2023">Unger et al 2023</a>] added to <a href="#sedt.Nomenclature">Nomenclature</a></div></li><li class="half_rhythm"><div>5 November 2020 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>11 June 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>15 February 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 April 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>10 February 2004 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 December 2003 (cd) Revision: change in test availability</div></li><li class="half_rhythm"><div>1 November 2001 (me) Review posted live</div></li><li class="half_rhythm"><div>16 May 2001 (gt) Original submission</div></li></ul></div></div><div id="sedt.References"><h2 id="_sedt_References_">References</h2><div id="sedt.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.fiedler.2004.103">Fiedler J, Le Merrer M, Mortier G, Heuertz S, Faivre L, Brenner RE. X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families. <span><span class="ref-journal">Hum Mutat. </span>2004;<span class="ref-vol">24</span>:103.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15221797" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15221797</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.g_cz.2000.242">Gécz J, Hillman MA, Gedeon AK, Cox TC, Baker E, Mulley JC. Gene structure and expression study of the SEDL gene for spondyloepiphyseal dysplasia tarda. <span><span class="ref-journal">Genomics. </span>2000;<span class="ref-vol">69</span>:242–51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11031107" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11031107</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.gedeon.1999.400">Gedeon AK, Colley A, Jamieson R, Thompson EM, Rogers J, Sillence D, Tiller GE, Mulley JC, Gecz J. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. <span><span class="ref-journal">Nat Genet. </span>1999;<span class="ref-vol">22</span>:400–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10431248" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10431248</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.gedeon.2001.1386">Gedeon AK, Tiller GE, Le Merrer M, Heuertz S, Tranebjaerg L, Chitayat D, Robertson S, Glass IA, Savarirayan R, Cole WG, Rimoin DL, Kousseff BG, Ohashi H, Zabel B, Munnich A, Gecz J, Mulley JC. The molecular basis of X-linked spondyloepiphyseal dysplasia tarda. <span><span class="ref-journal">Am J Hum Genet. </span>2001;<span class="ref-vol">68</span>:1386–97.</span> [<a href="/pmc/articles/PMC1226125/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1226125</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11349230" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11349230</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.huang.2022.389">Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. <span><span class="ref-journal">J Community Genet. </span>2022;<span class="ref-vol">13</span>:389–97.</span> [<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.jones.2013">Jones KL, Jones MC, del Campo M. <em>Smith's Recognizable Patterns of Human Malformation</em>. 7 ed. Philadelphia, PA: WB Saunders; 2013.</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.matsui.2001.328">Matsui Y, Yasui N, Ozono K, Yamagata M, Kawabata H, Yoshikawa H. Loss of the SEDL gene product (Sedlin) causes X-linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family. <span><span class="ref-journal">Am J Med Genet. </span>2001;<span class="ref-vol">99</span>:328–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11252002" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11252002</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.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="sedt.REF.rimoin.2013">Rimoin DL, Lachman RS, Unger S. Chondrodysplasias. In: Rimoin DL, Pyeritz RE, Korf BR, eds. <em>Emery & Rimoin’s Principles and Practice of Medical Genetics</em>. 6 ed. New York, NY: Academic Press; 2013.</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.shaw.2003.235">Shaw MA, Brunetti-Pierri N, Kadasi L, Kovacova V, Van Maldergem L, De Brasi D, Salerno M, Gecz J. Identification of three novel SEDL mutations, including mutation in the rare, non-canonical splice site of exon 4. <span><span class="ref-journal">Clin Genet. </span>2003;<span class="ref-vol">64</span>:235–42.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12919139" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12919139</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.shu.2002.106">Shu SG, Tsai CR, Chi CS. Spondyloepiphyseal dysplasia tarda: report of one case. <span><span class="ref-journal">Acta Paediatr Taiwan. </span>2002;<span class="ref-vol">43</span>:106–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12041616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12041616</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.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="sedt.REF.tiller.2001.1398">Tiller GE, Hannig VL, Dozier D, Carrel L, Trevarthen KC, Wilcox WR, Mundlos S, Haines JL, Gedeon AK, Gecz J. A recurrent RNA-splicing mutation in the SEDL gene causes X-linked spondyloepiphyseal dysplasia tarda. <span><span class="ref-journal">Am J Hum Genet. </span>2001;<span class="ref-vol">68</span>:1398–407.</span> [<a href="/pmc/articles/PMC1226126/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1226126</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11326333" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11326333</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.unger.2023">Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. <span><span class="ref-journal">Am J Med Genet A. </span>2023.</span> Epub ahead of print. [<a href="/pmc/articles/PMC10081954/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10081954</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36779427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36779427</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.venditti.2012.1668">Venditti R, Scanu T, Santoro M, Di Tullio G, Spaar A, Gaibisso R, Beznoussenko GV, Mironov AA, Mironov A Jr, Zelante L, Piemontese MR, Notarangelo A, Malhotra V, Vertel BM, Wilson C, De Matteis MA. Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. <span><span class="ref-journal">Science. </span>2012;<span class="ref-vol">337</span>:1668–72.</span> [<a href="/pmc/articles/PMC3471527/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3471527</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23019651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23019651</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.whyte.1999.9">Whyte MP, Gottesman GS, Eddy MC, McAlister WH. X-linked recessive spondyloepiphyseal dysplasia tarda. Clinical and radiographic evolution in a 6-generation kindred and review of the literature. <span><span class="ref-journal">Medicine (Baltimore). </span>1999;<span class="ref-vol">78</span>:9–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9990351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9990351</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sedt.REF.wynnedavies.1985.133">Wynne-Davies R, Gormley J. The prevalence of skeletal dysplasias. An estimate of their minimum frequency and the number of patients requiring orthopaedic care. <span><span class="ref-journal">J Bone Joint Surg Br. </span>1985;<span class="ref-vol">67</span>:133–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3155744" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3155744</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/NBK1145/?report=reader">PubReader</a></li><li><a href="/books/NBK1145/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1145" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1145" style="display:none" title="Cite this Page"><div class="bk_tt">Tiller GE. X-Linked Spondyloepiphyseal Dysplasia Tarda. 2001 Nov 1 [Updated 2023 Apr 6]. 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/NBK1145/pdf/Bookshelf_NBK1145.pdf">PDF version of this page</a> (580K)</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="#sedt.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#sedt.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#sedt.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#sedt.Genetically_Related_Allelic_Disorde" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#sedt.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#sedt.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#sedt.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#sedt.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#sedt.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#sedt.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#sedt.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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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=1463494" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=1463494" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=1463494" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=1463494" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301668" ref="ordinalpos=1&linkpos=1&log$=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> Hemophilia B.</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> Hemophilia B.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </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 class="brieflinkpopperctrl" href="/pubmed/24006547" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lichter-Konecki U, Caldovic L, Morizono H, Simpson K, Ah Mew N, MacLeod E. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301510" ref="ordinalpos=1&linkpos=3&log$=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> FBN1-Related Marfan Syndrome.</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> FBN1-Related Marfan Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Dietz H. </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 class="brieflinkpopperctrl" href="/pubmed/24830047" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Autosomal Dominant TRPV4 Disorders.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Autosomal Dominant TRPV4 Disorders.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">McCray BA, Schindler A, Hoover-Fong JE, Sumner CJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301578" ref="ordinalpos=1&linkpos=5&log$=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> Hemophilia A.</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> Hemophilia A.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </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=20301324" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=20301324" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d5ae9c67c23b31e035dda0">X-Linked Spondyloepiphyseal Dysplasia Tarda - GeneReviews®</a><div class="ralinkpop offscreen_noflow">X-Linked Spondyloepiphyseal Dysplasia Tarda - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d5ae9b67c23b31e035da2c">Table 6. [Notable Recurrent TRAPPC2 Pathogenic Variants]. - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Table 6. [Notable Recurrent TRAPPC2 Pathogenic Variants]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d5ae9a67c23b31e035d916">Table B. [OMIM Entries for X-Linked Spondyloepiphyseal Dysplasia Tarda (View All...</a><div class="ralinkpop offscreen_noflow">Table B. [OMIM Entries for X-Linked Spondyloepiphyseal Dysplasia Tarda (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d5ae9284f3725e59b2913b">RecName: Full=Trafficking protein particle complex subunit 2; AltName: Full=Sedl...</a><div class="ralinkpop offscreen_noflow">RecName: Full=Trafficking protein particle complex subunit 2; AltName: Full=Sedlin<div class="brieflinkpopdesc">gi|347662477|sp|P0DI81.1|TPC2A_HUMA</div></div><div class="tertiary">Protein</div></li><li class="ra_qry two_line"><a class="htb" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d5ae8084f3725e59b24e85">related_functional_gene_6399[group] AND (alive[prop]) <span class="number">(9)</span></a><div class="tertiary">Gene</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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