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<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK597768" /><meta name="ncbi_domain" content="gene" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK597768/" /><meta name="ncbi_pagename" content="MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
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<title>MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes - GeneReviews® - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/11/30" /><meta name="citation_author" content="Hua Wang" /><meta name="citation_author" content="Andrea Wierenga" /><meta name="citation_author" content="Sandeep Prabhu" /><meta name="citation_author" content="Klaas Wierenga" /><meta name="citation_pmid" content="38048414" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK597768/" /><meta name="citation_keywords" content="Spondyloepiphyseal Dysplasia, Kondo-Fu Type (SEDKF)" /><meta name="citation_keywords" content="Spondyloepiphyseal Dysplasia, Kondo-Fu Type (SEDKF)" /><meta name="citation_keywords" content="Membrane-bound transcription factor site-1 protease" /><meta name="citation_keywords" content="MBTPS1" /><meta name="citation_keywords" content="MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Hua Wang" /><meta name="DC.Contributor" content="Andrea Wierenga" /><meta name="DC.Contributor" content="Sandeep Prabhu" /><meta name="DC.Contributor" content="Klaas Wierenga" /><meta name="DC.Date" content="2023/11/30" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK597768/" /><meta name="description" content="MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (MBTPS1-SEMD) is characterized by postnatal-onset short stature, chest deformity (pectus carinatum or pectus excavatum), kyphosis and/or scoliosis, reduced bone density, inguinal hernia, protruding abdomen, cataracts, developmental delay, and dysmorphic facial features (prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent ears). Additional features can include waddling or staggering gait, craniosynostosis, mild intellectual disability, and seizures. Imaging findings include diffuse osteopenia, copper-beaten appearance of the skull, dysplasia of multiple thoracolumbar vertebrae, long bones with small and irregular epiphyses and mildly enlarged and irregular metaphyses, hip dysplasia with small fragmented sclerotic femoral heads, and short metacarpals and metatarsals with small epiphyses. Increased concentration of multiple lysosomal hydrolase enzymes can be identified in plasma and dried blood spots." /><meta name="og:title" content="MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes" /><meta name="og:type" content="book" /><meta name="og:description" content="MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (MBTPS1-SEMD) is characterized by postnatal-onset short stature, chest deformity (pectus carinatum or pectus excavatum), kyphosis and/or scoliosis, reduced bone density, inguinal hernia, protruding abdomen, cataracts, developmental delay, and dysmorphic facial features (prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent ears). Additional features can include waddling or staggering gait, craniosynostosis, mild intellectual disability, and seizures. Imaging findings include diffuse osteopenia, copper-beaten appearance of the skull, dysplasia of multiple thoracolumbar vertebrae, long bones with small and irregular epiphyses and mildly enlarged and irregular metaphyses, hip dysplasia with small fragmented sclerotic femoral heads, and short metacarpals and metatarsals with small epiphyses. Increased concentration of multiple lysosomal hydrolase enzymes can be identified in plasma and dried blood spots." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK597768/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/mbtps1-semd/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK597768/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
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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="#__NBK597768_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK597768_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/mbd5-dis/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/rett/" 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="_NBK597768_"><span class="title" itemprop="name"><i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Spondyloepiphyseal Dysplasia, Kondo-Fu Type (SEDKF)</div><p class="contrib-group"><span itemprop="author">Hua Wang</span>, MD, PhD, <span itemprop="author">Andrea Wierenga</span>, PhD, <span itemprop="author">Sandeep Prabhu</span>, MD, and <span itemprop="author">Klaas Wierenga</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK597768_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK597768_ai__"><div class="contrib half_rhythm"><span itemprop="author">Hua Wang</span>, MD, PhD<div class="affiliation small">School of Medicine<br />Loma Linda University<br />Loma Linda, California<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.ull@gnawauh" class="oemail">ude.ull@gnawauh</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Andrea Wierenga</span>, PhD<div class="affiliation small">SIVOTEC Bioinformatics<br />Boca Raton, Florida<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="hcet.aneg@agnereiwa" class="oemail">hcet.aneg@agnereiwa</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Sandeep Prabhu</span>, MD<div class="affiliation small">Department of Radiology<br />University of Oklahoma<br />Oklahoma City, Oklahoma<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.cshuo@uhbarp-peednas" class="oemail">ude.cshuo@uhbarp-peednas</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Klaas Wierenga</span>, MD<div class="affiliation small">Department of Clinical Genomics<br />Mayo Clinic Florida<br />Jacksonville, Florida<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.oyam@saalk.agnereiw" class="oemail">ude.oyam@saalk.agnereiw</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">November 30, 2023</span>.</p><p><em>Estimated reading time: 20 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="mbtps1-semd.Summary" itemprop="description"><h2 id="_mbtps1-semd_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD) is characterized by postnatal-onset short stature, chest deformity (pectus carinatum or pectus excavatum), kyphosis and/or scoliosis, reduced bone density, inguinal hernia, protruding abdomen, cataracts, developmental delay, and <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> facial features (prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent ears). Additional features can include waddling or staggering gait, craniosynostosis, mild intellectual disability, and seizures. Imaging findings include diffuse osteopenia, copper-beaten appearance of the skull, dysplasia of multiple thoracolumbar vertebrae, long bones with small and irregular epiphyses and mildly enlarged and irregular metaphyses, hip dysplasia with small fragmented sclerotic femoral heads, and short metacarpals and metatarsals with small epiphyses. Increased concentration of multiple lysosomal hydrolase enzymes can be identified in plasma and dried blood spots.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>MBTPS1</i>-SEMD is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic clinical and radiographic findings, elevated lysosomal hydrolase enzymes in plasma or dried blood spots, and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>MBTPS1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management of kyphoscoliosis, scoliosis, and hip dysplasia per orthopedist; vitamin D and calcium for reduced bone density; treatment of craniosynostosis per craniofacial specialist; surgical repair per surgeon and/or gastroenterologist for hernia; surgical removal of cataract per ophthalmologist; physical therapy to maximize mobility and reduce the risk for later-onset orthopedic complications; developmental and educational support.</p><p><i>Surveillance:</i> Annual growth assessment, orthopedic evaluation, ophthalmological evaluation, and assessment of developmental progress and educational needs; clinical assessment for hernia as needed.</p><p><i>Agents/circumstances to avoid:</i> In children with significant kyphoscoliosis, sports that place stress on the spine (e.g., heavy lifting, weight-bearing exercises) should be avoided.</p><p><i>Pregnancy management:</i> Although no pregnancies have been reported in individuals with <i>MBTPS1</i>-SEMD, pregnancy and delivery may be complicated in individuals with significant short stature and skeletal dysplasia; delivery by cesarean section may be necessary.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>MBTPS1</i>-SEMD is inherited in <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier. Once the <i>MBTPS1</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> for at-risk relatives and prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="mbtps1-semd.Diagnosis"><h2 id="_mbtps1-semd_Diagnosis_">Diagnosis</h2><div id="mbtps1-semd.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD) <b>should be suspected</b> in probands with the following clinical, laboratory, and imaging findings.</p><p><b>Clinical findings</b> (See <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F1/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF1" rid-ob="figobmbtps1semdF1">Figures 1</a> and <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F2/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF2" rid-ob="figobmbtps1semdF2">2</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF1" co-legend-rid="figlgndmbtps1semdF1"><a href="/books/NBK597768/figure/mbtps1-semd.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF1" rid-ob="figobmbtps1semdF1"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image001.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image001.jpg" alt="Figure 1. . Craniofacial features of several children with MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes." /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF1"><h4 id="mbtps1-semd.F1"><a href="/books/NBK597768/figure/mbtps1-semd.F1/?report=objectonly" target="object" rid-ob="figobmbtps1semdF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Craniofacial features of several children with <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes. Characteristic features include prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent <a href="/books/NBK597768/figure/mbtps1-semd.F1/?report=objectonly" target="object" rid-ob="figobmbtps1semdF1">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF2" co-legend-rid="figlgndmbtps1semdF2"><a href="/books/NBK597768/figure/mbtps1-semd.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF2" rid-ob="figobmbtps1semdF2"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image002.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF2"><h4 id="mbtps1-semd.F2"><a href="/books/NBK597768/figure/mbtps1-semd.F2/?report=objectonly" target="object" rid-ob="figobmbtps1semdF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Clinical features of several children with <i>MBTPS1</i>-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes A. Affected child at age six years with kyphoscoliosis (black arrows point to the prominent spinous processes)</p></div></div><ul><li class="half_rhythm"><div>Postnatal-onset short stature</div></li><li class="half_rhythm"><div>Kyphosis and/or scoliosis</div></li><li class="half_rhythm"><div>Inguinal hernia</div></li><li class="half_rhythm"><div>Protruding abdomen</div></li><li class="half_rhythm"><div>Cataracts (often <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a>)</div></li><li class="half_rhythm"><div>Developmental delay (gross motor and/or speech)</div></li><li class="half_rhythm"><div>Dysmorphic facial features, including prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent ears</div></li></ul><p>
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<b>Laboratory findings</b>
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</p><ul><li class="half_rhythm"><div><b>Increased concentration</b> of multiple lysosomal hydrolase enzymes in <b>plasma</b> and <b>dried blood spots</b> including alpha-fucosidase, alpha-glucosidase, alpha-iduronidase, alpha-mannosidase, beta-glucuronidase, beta-hexosaminidase, and beta-mannosidase [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>, <a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>]</div></li><li class="half_rhythm"><div><b>Increased activity</b> of lysosomal enzymes including alpha-N-acetylgalactosaminidase, alpha-N-acetylglucosaminidase, beta-glucuronidase, total beta-hexosaminidases, hexosaminidase A (MUGS substrate), and iduronate-2-sulfatase in <b>plasma</b>, but <b>normal activity in leukocytes</b> [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>]</div></li></ul><p><b>Imaging findings</b> [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>, <a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>, <a class="bk_pop" href="#mbtps1-semd.REF.chen.2023.1068718">Chen et al 2023</a>, <a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>] (See <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F3/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF3" rid-ob="figobmbtps1semdF3">Figures 3</a>, <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F4/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF4" rid-ob="figobmbtps1semdF4">4</a>, <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F5/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF5" rid-ob="figobmbtps1semdF5">5</a>, and <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F6/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF6" rid-ob="figobmbtps1semdF6">6</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF3" co-legend-rid="figlgndmbtps1semdF3"><a href="/books/NBK597768/figure/mbtps1-semd.F3/?report=objectonly" target="object" title="Figure 3. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF3" rid-ob="figobmbtps1semdF3"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image003.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image003.jpg" alt="Figure 3. . Radiographs of a child with MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes, age 37 months, with diffuse osteopenia; ovoid lumbar vertebral bodies; irregular aspect of cervical vertebral bodies, with mild reduction of vertebrae height; metaphyseal and epiphyseal irregularities of the long bones; mild metaphyseal enlargement; small epiphysis of the tubular bones; and copper-beaten skull." /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF3"><h4 id="mbtps1-semd.F3"><a href="/books/NBK597768/figure/mbtps1-semd.F3/?report=objectonly" target="object" rid-ob="figobmbtps1semdF3">Figure 3. </a></h4><p class="float-caption no_bottom_margin">Radiographs of a child with <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes, age 37 months, with diffuse osteopenia; ovoid lumbar vertebral bodies; irregular aspect of cervical vertebral bodies, with mild reduction of vertebrae <a href="/books/NBK597768/figure/mbtps1-semd.F3/?report=objectonly" target="object" rid-ob="figobmbtps1semdF3">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF4" co-legend-rid="figlgndmbtps1semdF4"><a href="/books/NBK597768/figure/mbtps1-semd.F4/?report=objectonly" target="object" title="Figure 4. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF4" rid-ob="figobmbtps1semdF4"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image004.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image004.jpg" alt="Figure 4. " /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF4"><h4 id="mbtps1-semd.F4"><a href="/books/NBK597768/figure/mbtps1-semd.F4/?report=objectonly" target="object" rid-ob="figobmbtps1semdF4">Figure 4. </a></h4><p class="float-caption no_bottom_margin">Radiographs of children with <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes showing diffuse osteopenia and metaphyseal sclerosis A. Irregularities more pronounced in the femoral heads, coxa vara, right hip dislocation <a href="/books/NBK597768/figure/mbtps1-semd.F4/?report=objectonly" target="object" rid-ob="figobmbtps1semdF4">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF5" co-legend-rid="figlgndmbtps1semdF5"><a href="/books/NBK597768/figure/mbtps1-semd.F5/?report=objectonly" target="object" title="Figure 5. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF5" rid-ob="figobmbtps1semdF5"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image005.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image005.jpg" alt="Figure 5. . Skull and spine radiographs of child, age six years, with MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes." /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF5"><h4 id="mbtps1-semd.F5"><a href="/books/NBK597768/figure/mbtps1-semd.F5/?report=objectonly" target="object" rid-ob="figobmbtps1semdF5">Figure 5. </a></h4><p class="float-caption no_bottom_margin">Skull and spine radiographs of child, age six years, with MBTPS1-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes. Straightened physiologic curvature of the cervical, thoracic, and lumbar spine. Irregular morphology and reduced <a href="/books/NBK597768/figure/mbtps1-semd.F5/?report=objectonly" target="object" rid-ob="figobmbtps1semdF5">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmbtps1semdF6" co-legend-rid="figlgndmbtps1semdF6"><a href="/books/NBK597768/figure/mbtps1-semd.F6/?report=objectonly" target="object" title="Figure 6. " class="img_link icnblk_img figpopup" rid-figpopup="figmbtps1semdF6" rid-ob="figobmbtps1semdF6"><img class="small-thumb" src="/books/NBK597768/bin/mbtps1-semd-Image006.gif" src-large="/books/NBK597768/bin/mbtps1-semd-Image006.jpg" alt="Figure 6. " /></a><div class="icnblk_cntnt" id="figlgndmbtps1semdF6"><h4 id="mbtps1-semd.F6"><a href="/books/NBK597768/figure/mbtps1-semd.F6/?report=objectonly" target="object" rid-ob="figobmbtps1semdF6">Figure 6. </a></h4><p class="float-caption no_bottom_margin">Radiographs and spine CT of child age 12 years with <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes A, B, E, F. No obvious abnormalities in long bones or lateral skull radiograph</p></div></div><ul><li class="half_rhythm"><div>Diffuse osteopenia</div></li><li class="half_rhythm"><div>Copper-beaten appearance of the skull</div></li><li class="half_rhythm"><div>Dysplasia of multiple thoracolumbar vertebrae: irregular cortex of the vertebrae (rough rather than smooth vertebral outline), end plate bone defects, ovoid lumbar vertebrae, and narrow intervertebral spaces [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>]</div></li><li class="half_rhythm"><div>Long bones with small and irregular epiphyses and mildly enlarged and irregular metaphyses; long bones may be short and bowed</div></li><li class="half_rhythm"><div>Significant hip dysplasia with small, fragmented sclerotic femoral heads</div></li><li class="half_rhythm"><div>Short metacarpals and metatarsals with small epiphyses [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>]</div></li></ul><p><b>Family history</b> is consistent with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance (e.g., affected sibs and/or parental <a class="def" href="/books/n/gene/glossary/def-item/consanguinity/">consanguinity</a>). Absence of a known family history does not preclude the diagnosis.</p></div><div id="mbtps1-semd.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>MBTPS1</i>-SEMD <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a href="#mbtps1-semd.Suggestive_Findings">suggestive clinical and radiographic findings</a>, elevated lysosomal hydrolase enzymes in plasma or dried blood spots, and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>MBTPS1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK597768/table/mbtps1-semd.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobmbtps1semdTmoleculargenetictesting">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#mbtps1-semd.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include any likely pathogenic variants. (2) Identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>MBTPS1</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>MBTPS1</i> pathogenic variant and one <i>MBTPS1</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#mbtps1-semd.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#mbtps1-semd.Option_2">Option 2</a>).</p><div id="mbtps1-semd.Option_1"><h4>Option 1</h4><p><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>MBTPS1</i> is performed first to detect <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 and small intragenic deletions/insertions. Typically, if only one or 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 <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> and whole-gene deletions or duplications; however, to date such variants have not been identified as a cause of this disorder.</p><p><b>A skeletal dysplasia or lysosomal disorders / mucopolysaccharidoses <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>MBTPS1</i> and other genes of interest (see <a href="#mbtps1-semd.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</p><p>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>.</p></div><div id="mbtps1-semd.Option_2"><h4>Option 2</h4><p>When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other skeletal dysplasias, <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="mbtps1-semd.T.molecular_genetic_testing" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.molecular_genetic_testing/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.molecular_genetic_testing_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mbtps1-semd.T.molecular_genetic_testing_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_mbtps1-semd.T.molecular_genetic_testing_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_mbtps1-semd.T.molecular_genetic_testing_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_mbtps1-semd.T.molecular_genetic_testing_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>MBTPS1</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.molecular_genetic_testing_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_mbtps1-semd.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>4</sup></td></tr><tr><td headers="hd_h_mbtps1-semd.T.molecular_genetic_testing_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_mbtps1-semd.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>4</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="mbtps1-semd.TF.1.1"><p class="no_margin">See <a href="/books/NBK597768/#mbtps1-semd.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="mbtps1-semd.TF.1.2"><p class="no_margin">See <a href="#mbtps1-semd.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="mbtps1-semd.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 <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 and small intragenic deletions/insertions; 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="mbtps1-semd.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="#mbtps1-semd.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="mbtps1-semd.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. Exome and <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a> may be able to detect deletions/duplications using breakpoint detection or read depth; however, <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> can be lower than gene-targeted deletion/duplication analysis.</p></div></dd></dl></div></div></div></div></div></div><div id="mbtps1-semd.Clinical_Characteristics"><h2 id="_mbtps1-semd_Clinical_Characteristics_">Clinical Characteristics</h2><div id="mbtps1-semd.Clinical_Description"><h3>Clinical Description</h3><p><i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD) is characterized by postnatal-onset short stature, pectus deformity, kyphosis and/or scoliosis, hernia, protruding abdomen, cataract(s), developmental delay, and <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> facial features, in combination with elevated lysosomal hydrolase enzyme levels in plasma. Additional features can include waddling or staggering gait, craniosynostosis, and seizures. To date six individuals with <i>MBTPS1</i>-SEMD from six families have been reported [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>, <a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>, <a class="bk_pop" href="#mbtps1-semd.REF.chen.2023.1068718">Chen et al 2023</a>, <a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>]. Three additional affected individuals are known to the authors. The features in <a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim/?report=objectonly" target="object" rid-ob="figobmbtps1semdTmbtps1relatedspondyloepim">Table 2</a> and the following description are based on published reports.</p><div id="mbtps1-semd.T.mbtps1related_spondyloepim" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.mbtps1related_spondyloepim_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Persons w/Feature</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Short stature</b>
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</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Chest deformity</b>
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</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pectus carinatum, pectus excavatum</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Kyphosis &/or scoliosis</b>
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</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hernia / protruding abdomen</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cataract</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Developmental delay</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl gross motor & speech delays</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dysmorphic facies</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Prominent forehead</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Prominent cheek bones</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Retromicrognathia</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Wide mouth</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Large ears</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al [2022]</a>, <a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al [2023]</a></p></div></dd></dl></div></div></div><p><b>Growth deficiency.</b> Postnatal-onset short stature was present in all reported individuals and was typically identified by age three years. Two individuals were treated with growth hormone therapy. One individual started treatment at age three years and discontinued after one year without improvement in growth velocity [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>]. In a second individual with normal insulin-like growth factor 1 (IGF-1), recombinant intravenous growth hormone (rhGH) of 0.15-0.2 IU/kg per day was started at age three years; after three years of rhGH therapy, the height increased from 5.3 standard deviations (SD) below the mean (before treatment) to 3.96 SD below the mean (after three years of treatment) [<a class="bk_pop" href="#mbtps1-semd.REF.chen.2022.e14904">Chen et al 2022</a>]. The range of severity of growth deficiency following treatment with growth hormone was from 2.9 to 5.3 SD below the mean.</p><p><b>Musculoskeletal manifestations.</b> Chest deformity including pectus carinatum, pectus excavatum, or unspecified sternal malformation was reported in all individuals. Kyphoscoliosis or scoliosis was present in all individuals. Reduced bone density was evident in all individuals. Anterolisthesis of L5 on S1 has been described in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>].</p><p>Hip dislocation with coxa vara was reported in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>]. Waddling or staggering gait was reported in two individuals [<a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>, <a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>].</p><p>Craniosynostosis was identified in two individuals [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>], including one individual originally reported by <a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al [2018]</a> with craniosynostosis identified after images were reevaluated by the authors.</p><p>Short neck and rhizomelia were reported in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>]; brachydactyly, genu valgum, valgus tibial bowing, and pes cavus were reported in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>]; pes valgus and prominent sandal grooves were reported in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>] (see <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F2/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF2" rid-ob="figobmbtps1semdF2">Figure 2</a>). Hyperextended fingers were reported in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>].</p><p><b>Hernia or protruding abdomen</b> were reported in all individuals. Bilateral inguinal hernia was reported in two individuals [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>] and unilateral inguinal hernia with protruding navel in one individual [<a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>]. Three individuals had protruding abdomen [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>, <a class="bk_pop" href="#mbtps1-semd.REF.chen.2022.e14904">Chen et al 2022</a>].</p><p><b>Cataracts</b> were common. Two individuals had <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> lamellar cataract, with surgical lens removed at age ten months [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>] and age 35 months [<a class="bk_pop" href="#mbtps1-semd.REF.chen.2022.e14904">Chen et al 2022</a>]. One individual had punctiform opacities of the lens identified at age 11 years, keratoconus that was treated at age 11 years, and anterior and posterior subcapsular cataract that was detected at age 18 years [<a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>].</p><p><b>Developmental delays.</b> Most individuals had gross motor delays. Three individuals started walking at age 15 months, 24 months, and 36 months [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>]. Three individuals had speech and language delay [<a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>, <a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>]; one of these children had first sounds at age 21 months and feeding problems with poor weight gain managed with gastrostomy tube feeding for several months [<a class="bk_pop" href="#mbtps1-semd.REF.meyer.2020.2727">Meyer et al 2020</a>]. One individual was reported to have expressive language delay, with first words spoken at age 26 months [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>].</p><p><b>Intelligence</b> is normal in the majority of individuals. One individual was reported with below-average intelligence [<a class="bk_pop" href="#mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi et al 2022</a>], and a second individual had mild intellectual disability with an IQ of 57 [<a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>].</p><p><b>Dysmorphic features.</b> Characteristic <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features were present in the majority of individuals, including prominent forehead, prominent cheekbones, retromicrognathia, wide mouth, and large, prominent ears (see <a class="figpopup" href="/books/NBK597768/figure/mbtps1-semd.F1/?report=objectonly" target="object" rid-figpopup="figmbtps1semdF1" rid-ob="figobmbtps1semdF1">Figure 1</a>).</p><p>
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<b>Other features</b>
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</p><ul><li class="half_rhythm"><div>Generalized seizure activity (1 individual) [<a class="bk_pop" href="#mbtps1-semd.REF.carvalho.2020.1796">Carvalho et al 2020</a>]</div></li><li class="half_rhythm"><div>Accumulation of fat on the chest and abdomen (1 individual) [<a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>]</div></li><li class="half_rhythm"><div>Epicanthal folds and high nasal bridge (1 individual) [<a class="bk_pop" href="#mbtps1-semd.REF.yuan.2023.1056141">Yuan et al 2023</a>]</div></li></ul></div><div id="mbtps1-semd.GenotypePhenotype_Correlatio"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been identified.</p></div><div id="mbtps1-semd.Prevalence"><h3>Prevalence</h3><p>The prevalence of this condition is unknown. To date, only six individuals from six families have been reported in literature. There are an additional three individuals known to the authors, including an affected fetus.</p></div></div><div id="mbtps1-semd.Genetically_Related_Allelic"><h2 id="_mbtps1-semd_Genetically_Related_Allelic_">Genetically Related (Allelic) Disorders</h2><p><b>Cataract, alopecia, oral mucosal disorders, and psoriasis-like (CAOP) syndrome.</b> Early-onset bilateral cataracts, generalized nonscarring alopecia, oral mucosal disorder (red and swollen gums), and severe psoriasiform skin lesions (affecting the scalp, face, inguinal region, buttocks, and lower extremities) were described in two individuals with <a class="def" href="/books/n/gene/glossary/def-item/compound-heterozygous/">compound heterozygous</a> pathogenic variants in <i>MBTPS1</i> including one stop loss variant [<a class="bk_pop" href="#mbtps1-semd.REF.chen.2022.e14904">Chen et al 2022</a>]. It is unclear if lysosomal hydrolase enzymes are elevated in CAOP syndrome; in one of the reported individuals, elevated hydrolases were not detected.</p><p><b>HyperCKemia and focal myoedema</b> were reported in one individual with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> [<a class="bk_pop" href="#mbtps1-semd.REF.schweitzer.2019.e00733">Schweitzer et al 2019</a>].</p></div><div id="mbtps1-semd.Differential_Diagnosis"><h2 id="_mbtps1-semd_Differential_Diagnosis_">Differential Diagnosis</h2><div id="mbtps1-semd.T.genes_of_interest_in_the_d" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of <i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.genes_of_interest_in_the_d/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.genes_of_interest_in_the_d_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Selected Features of Disorder</th></tr><tr><th headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4" id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical</th><th headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4" id="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Radiographic</th></tr></thead><tbody><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genetically heterogeneous <sup>1</sup></td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rss/">Silver-Russell syndrome</a>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Growth deficiency</div></li><li class="half_rhythm"><div>Relative macrocephaly</div></li><li class="half_rhythm"><div>Frontal bossing or prominent forehead</div></li><li class="half_rhythm"><div>Body asymmetry</div></li></ul>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ARSE</i>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<a href="/books/n/gene/cdp1-xlr/">Chondrodysplasia punctata 1, X-linked</a>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Brachytelephalangy</div></li><li class="half_rhythm"><div>Nasomaxillary hypoplasia</div></li><li class="half_rhythm"><div>Postnatal short stature</div></li></ul>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Stippled epiphyses</div></li><li class="half_rhythm"><div>Calcifications</div></li><li class="half_rhythm"><div>Vertebral abnormalities</div></li></ul>
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</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>COL2A1</i>
|
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spondyloepiphyseal dysplasia congenita (SEDC), <i>COL2A1-</i>related (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_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_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe disproportionate short stature, short extremities</div></li><li class="half_rhythm"><div>Hypertelorism, flat profile, Pierre Robin sequence</div></li><li class="half_rhythm"><div>Myopia & hearing loss</div></li></ul>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Delayed/poor ossification of vertebrae & pubic bones</div></li><li class="half_rhythm"><div>Short long bones w/hypoplastic epiphyses</div></li><li class="half_rhythm"><div>↑ risk for cervical instability & spinal cord compression</div></li></ul>
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</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Spondyloperipheral dysplasia, <i>COL2A1-</i>related (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mild-to-moderate disproportionate short stature & short extremities</div></li><li class="half_rhythm"><div>Brachydactyly type E, short ulnae, variable clubfeet, cleft palate</div></li><li class="half_rhythm"><div>Myopia & hearing loss</div></li></ul>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ovoid vertebra</div></li><li class="half_rhythm"><div>Delayed ossification of pubic bones</div></li><li class="half_rhythm"><div>Flattened & irregular epiphyses in long bones</div></li><li class="half_rhythm"><div>Premature hip arthrosis causes joint pain.</div></li></ul>
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</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Kniest dysplasia, <i>COL2A1-</i>related (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe disproportionate short stature, short neck, short thorax, short extremities</div></li><li class="half_rhythm"><div>Myopia, vitreous abnormalities, & retinal detachment</div></li></ul>
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Platyspondyly w/anterior wedging & coronal clefting of lumbar vertebral bodies</div></li><li class="half_rhythm"><div>Delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers</div></li><li class="half_rhythm"><div>Short long bones w/large metaphyses & epiphyses</div></li></ul>
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</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Spondyloepimetaphyseal dysplasia, <i>COL2A1-</i>related (See <a href="/books/n/gene/collagen-2/">Type II Collagen Disorders Overview</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infants initially present w/same findings as those w/SEDC.</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Metaphyseal flaring becomes evident in 1st yr of life.</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>EBP</i>
|
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/x-dcdp/">Chondrodysplasia punctata 2, X-linked</a>
|
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</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Growth deficiency</div></li><li class="half_rhythm"><div>Frontal bossing; depressed nasal bridge; sparse eyebrows & lashes, often asymmetric</div></li><li class="half_rhythm"><div>Rhizomelia</div></li><li class="half_rhythm"><div>Scoliosis</div></li><li class="half_rhythm"><div>Abnormalities of skin, hair, & nails; ocular anomaly</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Stippling involving epiphyses of long bones & vertebrae, trachea, & distal ends of ribs</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GALNS</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/mps4a/">Mucopolysaccharidosis type IVA</a>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Marked disproportionate short stature w/short trunk</div></li><li class="half_rhythm"><div>Ulnar deviation of wrists</div></li><li class="half_rhythm"><div>Pectus carinatum & flaring of lower rib cage</div></li><li class="half_rhythm"><div>Gibbus, kyphosis, & scoliosis</div></li><li class="half_rhythm"><div>Genu valgum</div></li><li class="half_rhythm"><div>Hypermobile joints</div></li><li class="half_rhythm"><div>Waddling gait w/frequent falls</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Odontoid hypoplasia w/subsequent cervical instability</div></li><li class="half_rhythm"><div>Short ulnas & delayed bone maturation</div></li><li class="half_rhythm"><div>Short metacarpals</div></li><li class="half_rhythm"><div>Flared iliac wings, flattening of femoral epiphyses, & coxa valga</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GLB1</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mucopolysaccharidosis type IVB (MPS IVB) (See <a href="/books/n/gene/gm1-ganglio/"><i>GLB1</i>-Related Disorders</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short stature (below 15th centile in adults)</div></li><li class="half_rhythm"><div>Kyphoscoliosis</div></li><li class="half_rhythm"><div>Joint laxity</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Axial & appendicular dysostosis multiplex</div></li><li class="half_rhythm"><div>Platyspondyly</div></li><li class="half_rhythm"><div>Odontoid hypoplasia</div></li><li class="half_rhythm"><div>Coxa/genu valga</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GNPTAB</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mucolipidosis II (See <a href="/books/n/gene/ml2/"><i>GNPTAB</i>-Related Disorders</a>.)</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In neonatal period:
|
||
<ul><li class="half_rhythm"><div>Small to low-normal anthropometric measurements for gestational age</div></li><li class="half_rhythm"><div>Restricted range of passive motion in shoulders</div></li><li class="half_rhythm"><div>Flat face, shallow orbits, depressed nasal bridge</div></li><li class="half_rhythm"><div>Thick skin w/wax-like texture</div></li><li class="half_rhythm"><div>Variable musculoskeletal findings</div></li></ul>
|
||
Note: Activity of multiple lysosomal hydrolases is ↑ in plasma, dried blood, & other body fluids.</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe dysostosis multiplex</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GNPTG</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/ml3c/">Mucolipidosis III gamma</a>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Growth rate deceleration</div></li><li class="half_rhythm"><div>Joint stiffness of fingers, shoulders, & hips</div></li><li class="half_rhythm"><div>Gradual mild coarsening of facial features</div></li><li class="half_rhythm"><div>Genu valgum</div></li><li class="half_rhythm"><div>Spinal deformities incl scoliosis & hyperlordosis</div></li><li class="half_rhythm"><div>No organomegaly</div></li></ul>
|
||
Note: Activity of nearly all lysosomal hydrolases is up to 10x higher than normal in plasma, dried blood, & other body fluids.</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mild-to-moderate dysostosis multiplex</div></li><li class="half_rhythm"><div>Hypoplastic iliac bones w/flared iliac wings</div></li><li class="half_rhythm"><div>Shallow & irregular acetabula & moderate-to-severe dysplasia of proximal femoral epiphyses giving rise to coxa valga</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TRAPPC2</i>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/sedt/">X-linked spondyloepiphyseal dysplasia tarda</a> (SED-XL), <i>TRAPPC2-</i>related</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Disproportionate short stature in adolescence or adulthood w/short trunk & barrel-shaped chest.</div></li><li class="half_rhythm"><div>Short neck, dorsal kyphosis, scoliosis, & lumbar hyperlordosis may be evident by puberty.</div></li><li class="half_rhythm"><div>Early-onset osteoarthritis</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_1_4 hd_h_mbtps1-semd.T.genes_of_interest_in_the_d_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Multiple epiphyseal abnormalities</div></li><li class="half_rhythm"><div>Platyspondyly; characteristic superior & inferior "humping" on lateral radiograph</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></ul>
|
||
</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>; DD = developmental delay; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; SEDC = spondyloepiphyseal dysplasia congenita; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd><dt>1. </dt><dd><div id="mbtps1-semd.TF.3.1"><p class="no_margin">Hypomethylation of the <a class="def" href="/books/n/gene/glossary/def-item/imprinted/">imprinted</a> control region 1 (ICR1) at 11p15.5 causes Silver-Russell syndrome (SRS) in 35%-50% of individuals; maternal <a class="def" href="/books/n/gene/glossary/def-item/uniparental-disomy/">uniparental disomy</a> causes SRS in 7%-10% of individuals. A small number of affected individuals have duplications, deletions, or translocations involving the <a class="def" href="/books/n/gene/glossary/def-item/imprinting/">imprinting</a> centers at 11p15.5 or duplications, deletions, or translocations involving <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 7. Rarely, SRS is caused by pathogenic variants in <i>CDKN1C</i>, <i>IGF2</i>, <i>PLAG1</i>, or <i>HMGA2</i>. Accurate assessment of SRS <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> requires identification of the causative genetic mechanism in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</p></div></dd><dt>2. </dt><dd><div id="mbtps1-semd.TF.3.2"><p class="no_margin">Type II collagen disorders are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. However, rare instances of <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance in spondyloepiphyseal dysplasia congenita have been reported.</p></div></dd></dl></div></div></div></div><div id="mbtps1-semd.Management"><h2 id="_mbtps1-semd_Management_">Management</h2><p>No clinical practice guidelines for <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD) have been published.</p><div id="mbtps1-semd.Evaluations_Following_Initia"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>MBTPS1</i>-SEMD, the evaluations summarized in <a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_1/?report=objectonly" target="object" rid-ob="figobmbtps1semdTmbtps1relatedspondyloepim1">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="mbtps1-semd.T.mbtps1related_spondyloepim_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.mbtps1related_spondyloepim_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concerns</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_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_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth/Nutrition</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assess growth.</div></li><li class="half_rhythm"><div>Gastroenterology / nutrition / feeding team eval</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider eval for gastrostomy tube placement in those w/feeding issues & poor weight gain for height in early childhood</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skeletal survey</div></li><li class="half_rhythm"><div>Orthopedist / PT & OT eval</div></li><li class="half_rhythm"><div>DXA scan</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for skeletal manifestations incl chest deformity, spine abnormalities, hip dysplasia, & craniosynostosis w/additional imaging as needed</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hernia</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">General surgery eval in those w/inguinal hernia</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval to assess for cataract</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental eval inclu gross & fine motor, speech & language, cognitive & performance, & activities of daily living</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_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_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>MBTPS1</i>-SEMD to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By clinicians, wider care team, & family support organizations</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#mbtps1-semd.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a></div></li><li class="half_rhythm"><div>Social work involvement for parental support</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DXA = dual x-ray absorptiometry; <i>MBTPS1</i>-SEMD = <i>MBTPS1</i>-related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="mbtps1-semd.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="mbtps1-semd.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p><b>Supportive care</b> to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_2/?report=objectonly" target="object" rid-ob="figobmbtps1semdTmbtps1relatedspondyloepim2">Table 5</a>).</p><div id="mbtps1-semd.T.mbtps1related_spondyloepim_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.mbtps1related_spondyloepim_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth deficiency</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>GH therapy can be tried, but outcome is uncertain.</div></li><li class="half_rhythm"><div>It is unknown if GH therapy can lead to worsening of disproportionate growth in those w/spinal dysplasia.</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GH therapy improved growth velocity in 1 person, <sup>1</sup> there was no benefit in another person. <sup>2</sup></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Kyphoscoliosis/</b>
|
||
<br />
|
||
<b>Scoliosis</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Operative mgmt may be warranted in those w/neurologic manifestations.</div></li><li class="half_rhythm"><div>In those w/o neurologic compromise, procedures such as vertebroplasty & kyphoplasty may be considered for vertebral augmentation.</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Operative mgmt may be indicated in those who have failed conservative therapy, experience intractable pain, have an onset of neurologic changes, or have persistent progression despite bracing.</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Reduced bone density</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vitamin D & calcium may be used as a supplement for reduced bone density.</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hip dysplasia</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Craniosynostosis</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per craniofacial specialist</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hernia</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair per surgeon &/or gastroenterologist</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cataract</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical removal of cataract per ophthalmologist</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical therapy</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To maximize mobility & reduce risk for later-onset orthopedic complications (e.g., scoliosis)</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental & educational support incl:
|
||
<ul><li class="half_rhythm"><div>Early intervention programs</div></li><li class="half_rhythm"><div>Early childhood education</div></li><li class="half_rhythm"><div>Early & periodic screening, diagnosis, & treatment (EPSDT)</div></li></ul>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">GH = growth hormone</p></div></dd><dt>1. </dt><dd><div id="mbtps1-semd.TF.5.1"><p class="no_margin">
|
||
<a class="bk_pop" href="#mbtps1-semd.REF.chen.2023.1068718">Chen et al [2023]</a>
|
||
</p></div></dd><dt>2. </dt><dd><div id="mbtps1-semd.TF.5.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al [2018]</a>
|
||
</p></div></dd></dl></div></div></div></div><div id="mbtps1-semd.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_3/?report=objectonly" target="object" rid-ob="figobmbtps1semdTmbtps1relatedspondyloepim3">Table 6</a> are recommended.</p><div id="mbtps1-semd.T.mbtps1related_spondyloepim_3" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>MBTPS1</i>-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.T.mbtps1related_spondyloepim_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.T.mbtps1related_spondyloepim_3_lrgtbl__"><table><thead><tr><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_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_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Short stature</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth assessment</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Kyphosis / Scoliosis /</b>
|
||
<br />
|
||
<b>Other skeletal manifestations</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedic eval</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hernia</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for hernia</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cataract</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay</b>
|
||
</td><td headers="hd_h_mbtps1-semd.T.mbtps1related_spondyloepim_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs</td></tr></tbody></table></div></div></div><div id="mbtps1-semd.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>In children with significant kyphoscoliosis, sports that place stress on the spine (e.g., heavy lifting, weight-bearing exercises) should be avoided.</p></div><div id="mbtps1-semd.Evaluation_of_Relatives_at_R"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#mbtps1-semd.Related_Genetic_Counseling_I">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="mbtps1-semd.Pregnancy_Management"><h3>Pregnancy Management</h3><p>No pregnancies have been reported in individuals with <i>MBTPS</i>-SEMD. Pregnancy and delivery may be complicated in individuals with significant short stature and skeletal dysplasia; delivery by cesarean section may be necessary.</p></div><div id="mbtps1-semd.Therapies_Under_Investigatio"><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="mbtps1-semd.Genetic_Counseling"><h2 id="_mbtps1-semd_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="mbtps1-semd.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div><div id="mbtps1-semd.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment.</div></li><li class="half_rhythm"><div>If a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> occurred as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the proband or as a <a class="def" href="/books/n/gene/glossary/def-item/postzygotic/">postzygotic</a> <i>de novo</i> event in a mosaic parent [<a class="bk_pop" href="#mbtps1-semd.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> that was not detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> with the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that resulted in homozygosity for the pathogenic variant in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for an <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The offspring of an individual with <i>MBTPS1</i>-SEMD are obligate heterozygotes (carriers) for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>MBTPS1</i>.</p><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of an <i>MBTPS1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="mbtps1-semd.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>MBTPS1</i> pathogenic variants in the family.</p></div><div id="mbtps1-semd.Related_Genetic_Counseling_I"><h3>Related Genetic Counseling Issues</h3><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="mbtps1-semd.Prenatal_Testing_and_Preimpl"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>MBTPS1</i> pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> 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="mbtps1-semd.Resources"><h2 id="_mbtps1-semd_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>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="mbtps1-semd.Molecular_Genetics"><h2 id="_mbtps1-semd_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="mbtps1-semd.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK597768/table/mbtps1-semd.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_mbtps1-semd.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_mbtps1-semd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/8720" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>MBTPS1</i>
|
||
</a>
|
||
</td><td headers="hd_b_mbtps1-semd.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=8720" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">16q23<wbr style="display:inline-block"></wbr>.3-q24.1</a>
|
||
</td><td headers="hd_b_mbtps1-semd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q14703" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Membrane-bound transcription factor site-1 protease</a>
|
||
</td><td headers="hd_b_mbtps1-semd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.LOVD.nl/MBTPS1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MBTPS1 @ LOVD</a>
|
||
</td><td headers="hd_b_mbtps1-semd.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=MBTPS1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MBTPS1</a>
|
||
</td><td headers="hd_b_mbtps1-semd.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MBTPS1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MBTPS1</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="mbtps1-semd.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>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="mbtps1-semd.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes (<a href="/omim/603355,618392" 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/NBK597768/table/mbtps1-semd.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mbtps1-semd.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603355" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603355</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MEMBRANE-BOUND TRANSCRIPTION FACTOR PROTEASE, SITE 1; MBTPS1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/618392" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">618392</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPONDYLOEPIPHYSEAL DYSPLASIA, KONDO-FU TYPE; SEDKF</td></tr></tbody></table></div></div><div id="mbtps1-semd.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Membrane-bound <a class="def" href="/books/n/gene/glossary/def-item/transcription-factor/">transcription factor</a> site-1 protease (MBTPS1; also known as S1P) is a serine protease located in the Golgi. MBTPS1 has been shown to regulate lipogenesis, endoplasmic reticulum (ER) function, and lysosome biogenesis in mice and cultured cells [<a class="bk_pop" href="#mbtps1-semd.REF.kondo.2018.e121596">Kondo et al 2018</a>]. Defective MBTPS1 function impairs activation of the ER stress transducer BBF2H7, leading to ER retention of collagen in chondrocytes. MBTPS1 deficiency also causes abnormal secretion of lysosomal enzymes due to partial impairment of mannose-6-phosphate-dependent delivery to lysosomes. Collectively, these abnormalities lead to apoptosis of chondrocytes and lysosomal enzyme-mediated degradation of the bone matrix.</p><p><b>Mechanism of disease causation.</b> Loss of function</p></div></div><div id="mbtps1-semd.Chapter_Notes"><h2 id="_mbtps1-semd_Chapter_Notes_">Chapter Notes</h2><div id="mbtps1-semd.Author_Notes"><h3>Author Notes</h3><p><b>Hua Wang, MD, PhD,</b> is a clinical geneticist. Her research interests are skeletal dysplasia and lysosomal storage disorders. She runs a skeletal dysplasia clinic and diagnoses and manages individuals with lysosomal storage disease as well as other genetic disorders.</p><p><b>Andrea Wierenga, PhD,</b> is a clinical biochemical geneticist. Her interest is exploring biochemical aspects of rare diseases and research associated with biochemical disorders.</p><p><b>Sandeep Prabhu, MD,</b> is a pediatric radiologist with interest and expertise in skeletal dysplasia.</p><p><b>Klaas Wierenga, MD,</b> is a clinical geneticist and medical biochemical geneticist. His research interest is rare disease diagnostics, with special interest in clinical homozygosity mapping.</p><p>Klaas Wierenga, MD, Hua Wang, MD, PhD, Lijun Xia, MD (<a href="mailto:dev@null" data-email="gro.frmo@aix-nujil" class="oemail">gro.frmo@aix-nujil</a>), and Patrick Gaffney, MD (<a href="mailto:dev@null" data-email="gro.frmo@yenffag-kcirtap" class="oemail">gro.frmo@yenffag-kcirtap</a>), are actively involved in clinical research regarding individuals with <i>MBTPS1-</i>related spondyloepimetaphyseal dysplasia with elevated lysosomal enzymes (<i>MBTPS1</i>-SEMD). They would be happy to communicate with persons who have any questions regarding diagnosis of <i>MBTPS1</i>-SEMD or other considerations.</p><p>Contact the previously mentioned physicians and researchers to inquire about review of <i>MBTPS1</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>.</p><p><b><i>MBTPS1</i>-Related Disorders Research Group</b><br />Phone: 405-271-6673<br />Web: <a href="https://omrf.org/mbtps-related-disorders-research-group/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">omrf.org/mbtps-related-disorders-research-group</a></p><p>This research group aims to increase the understanding of <i>MBTPS1</i>-SEMD. Physicians and families interested in obtaining more information are encouraged to reach out.</p></div><div id="mbtps1-semd.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the patients and families that have contributed to the accumulating information about <i>MBTPS</i>-SEMD.</p></div><div id="mbtps1-semd.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>30 November 2023 (sw) Review posted live</div></li><li class="half_rhythm"><div>24 July 2023 (kw) Original submission</div></li></ul></div></div><div id="mbtps1-semd.References"><h2 id="_mbtps1-semd_References_">References</h2><div id="mbtps1-semd.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="mbtps1-semd.REF.alotaibi.2022.5498109">Alotaibi
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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/NBK597768/?report=reader">PubReader</a></li><li><a href="/books/NBK597768/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK597768" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK597768" style="display:none" title="Cite this Page"><div class="bk_tt">Wang H, Wierenga A, Prabhu S, et al. MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes. 2023 Nov 30. 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/NBK597768/pdf/Bookshelf_NBK597768.pdf">PDF version of this page</a> (1.3M)</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="#mbtps1-semd.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#mbtps1-semd.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#mbtps1-semd.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#mbtps1-semd.Genetically_Related_Allelic" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#mbtps1-semd.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#mbtps1-semd.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#mbtps1-semd.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#mbtps1-semd.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#mbtps1-semd.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#mbtps1-semd.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#mbtps1-semd.References" ref="log$=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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href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=5534770" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=5534770" ref="log$=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/20301510" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> FBN1-Related Marfan Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> FBN1-Related Marfan Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Dietz H. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/23844448" ref="ordinalpos=1&linkpos=2&log$=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> Mucopolysaccharidosis Type IVA.</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> Mucopolysaccharidosis Type IVA.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Regier DS, Oetgen M, Tanpaiboon P. </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/20301599" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Beta-Thalassemia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Beta-Thalassemia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Langer AL. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301635" ref="ordinalpos=1&linkpos=4&log$=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> PLOD1-Related Kyphoscoliotic Ehlers-Danlos 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> PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Rohrbach M, Giunta C. </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/38190471" 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> Mucopolysaccharidosis Type VII.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span 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