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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Shprintzen-Goldberg Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2020/04/09" /><meta name="citation_author" content="Marie T Greally" /><meta name="citation_pmid" content="20301454" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1277/" /><meta name="citation_keywords" content="Ski oncogene" /><meta name="citation_keywords" content="SKI" /><meta name="citation_keywords" content="Shprintzen-Goldberg Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Shprintzen-Goldberg Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Marie T Greally" /><meta name="DC.Date" content="2020/04/09" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1277/" /><meta name="description" content="Shprintzen-Goldberg syndrome (SGS) is characterized by: delayed motor and cognitive milestones and mild-to-moderate intellectual disability; craniosynostosis of the coronal, sagittal, or lambdoid sutures; distinctive craniofacial features; and musculoskeletal findings including olichostenomelia, arachnodactyly, camptodactyly, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures, pes planus, foot malposition, and C1-C2 spine malformation. Cardiovascular anomalies may include mitral valve prolapse, secundum atrial septal defect, and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, and myopia are also characteristic findings." /><meta name="og:title" content="Shprintzen-Goldberg Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Shprintzen-Goldberg syndrome (SGS) is characterized by: delayed motor and cognitive milestones and mild-to-moderate intellectual disability; craniosynostosis of the coronal, sagittal, or lambdoid sutures; distinctive craniofacial features; and musculoskeletal findings including olichostenomelia, arachnodactyly, camptodactyly, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures, pes planus, foot malposition, and C1-C2 spine malformation. Cardiovascular anomalies may include mitral valve prolapse, secundum atrial septal defect, and aortic root dilatation. 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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="#__NBK1277_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1277_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/scad/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/sds/" 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="_NBK1277_"><span class="title" itemprop="name">Shprintzen-Goldberg Syndrome</span></h1><p class="contrib-group"><span itemprop="author">Marie T Greally</span>, MD, MSc, FACMG.</p><a data-jig="ncbitoggler" href="#__NBK1277_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1277_ai__"><div class="contrib half_rhythm"><span itemprop="author">Marie T Greally</span>, MD, MSc, FACMG<div class="affiliation small">Consultant Clinical Geneticist, Department of Clinical Genetics<br />Our Lady's Children's Hospital, Crumlin<br />Dublin, Ireland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.oohay@yllaerg.eiram" class="oemail">moc.oohay@yllaerg.eiram</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">January 13, 2006</span>; Last Update: <span itemprop="dateModified">April 9, 2020</span>.</p><p><em>Estimated reading time: 18 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="sgs.Summary" itemprop="description"><h2 id="_sgs_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Shprintzen-Goldberg syndrome (SGS) is characterized by: delayed motor and cognitive milestones and mild-to-moderate intellectual disability; craniosynostosis of the coronal, sagittal, or lambdoid sutures; distinctive craniofacial features; and musculoskeletal findings including olichostenomelia, arachnodactyly, camptodactyly, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures, pes planus, foot malposition, and C1-C2 spine malformation. Cardiovascular anomalies may include mitral valve prolapse, secundum atrial septal defect, and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, and myopia are also characteristic findings.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of SGS is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SKI</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> Early intervention for developmental delay with placement in special education programs; standard management of cleft palate and craniosynostosis; surgical fixation may be necessary for cervical spine instability; routine management for scoliosis; surgical correction for pectus excavatum is rarely indicated; physiotherapy for joint contractures; clubfoot deformity may require surgical correction. If aortic dilatation is present, treatment with beta-adrenergic blockers or other medications should be considered in order to reduce hemodynamic stress; surgical intervention for aneurysms may be indicated; treatment of myopia as per ophthalmologist; surgical repair of abdominal hernias as indicated.</p><p><i>Prevention of secondary complications:</i> Subacute bacterial endocarditis prophylaxis is recommended for dental work or other procedures for individuals with cardiac complications.</p><p><i>Surveillance:</i> Developmental assessment with each visit; cervical spine evaluation and clinical evaluation for scoliosis as recommended by orthopedist; imaging per cardiologist familiar with this condition; ophthalmology exams as recommended by ophthalmologist.</p><p><i>Agents/circumstances to avoid:</i> Contact sports; use of agents that stimulate the cardiovascular system; activities that may lead to joint pain and/or injury.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>SGS, caused by a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SKI</i>, is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder. Most individuals with SGS have unaffected parents, suggesting that the causative variant has occurred either as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the affected individual or as a result of <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in one of the parents. Affected sibs born to unaffected parents support the occurrence of germline mosaicism in some families with SGS. Once a <i>SKI</i> pathogenic variant has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="sgs.Diagnosis"><h2 id="_sgs_Diagnosis_">Diagnosis</h2><p>Formal diagnostic criteria for Shprintzen-Goldberg syndrome (SGS) have not been established.</p><div id="sgs.Suggestive_Findings"><h3>Suggestive Findings</h3><p>SGS <b>should be suspected</b> in individuals with a combination of the following clinical (see <a class="figpopup" href="/books/NBK1277/figure/sgs.F1/?report=objectonly" target="object" rid-figpopup="figsgsF1" rid-ob="figobsgsF1">Figure 1</a>) and radiographic features:</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figsgsF1" co-legend-rid="figlgndsgsF1"><a href="/books/NBK1277/figure/sgs.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figsgsF1" rid-ob="figobsgsF1"><img class="small-thumb" src="/books/NBK1277/bin/sgs-Image001.gif" src-large="/books/NBK1277/bin/sgs-Image001.jpg" alt="Figure 1. . Clinical features of Shprintzen-Goldberg syndrome." /></a><div class="icnblk_cntnt" id="figlgndsgsF1"><h4 id="sgs.F1"><a href="/books/NBK1277/figure/sgs.F1/?report=objectonly" target="object" rid-ob="figobsgsF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Clinical features of Shprintzen-Goldberg syndrome. Note craniosynostosis with typical craniofacial features including dolichocephaly, proptosis, hypertelorism, low-set ears, and retrognathia. Hand and foot images show arachnodactyly and camptodactyly. <a href="/books/NBK1277/figure/sgs.F1/?report=objectonly" target="object" rid-ob="figobsgsF1">(more...)</a></p></div></div><ul><li class="half_rhythm"><div><b>Neurodevelopment.</b> Hypotonia, delayed motor and cognitive milestones, mild-to-moderate intellectual disability</div></li><li class="half_rhythm"><div><b>Craniosynostosis</b> usually involving the coronal, sagittal, or lambdoid sutures</div></li><li class="half_rhythm"><div>
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<b>Craniofacial findings</b>
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</div><ul><li class="half_rhythm"><div>Dolichocephaly with or without scaphocephaly</div></li><li class="half_rhythm"><div>Tall or prominent forehead</div></li><li class="half_rhythm"><div>Hypertelorism</div></li><li class="half_rhythm"><div>Downslanting palpebral fissures</div></li><li class="half_rhythm"><div>Ocular proptosis</div></li><li class="half_rhythm"><div>Malar flattening</div></li><li class="half_rhythm"><div>High narrow palate with prominent palatine ridges</div></li><li class="half_rhythm"><div>Micrognathia and/or retrognathia</div></li><li class="half_rhythm"><div>Apparently low-set and posteriorly rotated ears</div></li></ul></li><li class="half_rhythm"><div>
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<b>Musculoskeletal findings</b>
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</div><ul><li class="half_rhythm"><div>Dolichostenomelia</div></li><li class="half_rhythm"><div>Arachnodactyly</div></li><li class="half_rhythm"><div>Camptodactyly</div></li><li class="half_rhythm"><div>Pectus excavatum or carinatum</div></li><li class="half_rhythm"><div>Scoliosis</div></li><li class="half_rhythm"><div>Joint hypermobility or contractures</div></li><li class="half_rhythm"><div>Pes planus</div></li><li class="half_rhythm"><div>Foot malposition/talipes equinovarus/club foot</div></li><li class="half_rhythm"><div>C1-C2 spine malformation</div></li></ul></li><li class="half_rhythm"><div><b>Cardiovascular anomalies.</b> Mitral valve prolapse/valvular anomalies, secundum atrial septal defect, aortic root dilatation</div></li><li class="half_rhythm"><div><b>Brain anomalies.</b> Chiari I malformation</div></li><li class="half_rhythm"><div><b>Other.</b> Minimal subcutaneous fat, abdominal wall defects, and myopia</div></li></ul></div><div id="sgs.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of SGS <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>SKI</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1277/table/sgs.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobsgsTmoleculargenetictestingusedin">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="#sgs.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>SKI</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis.</p><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/exome-array/">exome array</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Because the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of SGS is broad, individuals with the distinctive findings described in <a href="#sgs.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#sgs.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other inherited disorders with craniosynostosis and additional <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies are more likely to be diagnosed using genomic testing (see <a href="#sgs.Option_2">Option 2</a>).</p><div id="sgs.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of SGS, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>SKI</i> to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>SKI</i> and other genes of interest (see <a href="#sgs.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="sgs.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 inherited disorders characterized by craniosynostosis, <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (which does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>[s] are likely involved) is the best option. <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>If <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> is not diagnostic – and particularly when evidence supports <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance – <b><a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a></b> (when clinically available) may be considered to detect (multi)<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</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="sgs.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Number of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SKI</i>
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</td><td headers="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">44 <sup>4</sup></td></tr><tr><td headers="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_sgs.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="sgs.TF.1.1"><p class="no_margin">See <a href="/books/NBK1277/#sgs.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="sgs.TF.1.2"><p class="no_margin">See <a href="#sgs.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="sgs.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="sgs.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al [2012]</a>, <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al [2012]</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al [2014]</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al [2015]</a>, <a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al [2017]</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al [2019]</a>, <a class="bk_pop" href="#sgs.REF.zhang.2019.936">Zhang et al [2019]</a></p></div></dd><dt>5. </dt><dd><div id="sgs.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>6. </dt><dd><div id="sgs.TF.1.6"><p class="no_margin">Contiguous <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of <i>SKI</i> and adjacent genes has been reported in individuals with a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> that appears to be distinct from SGS (see <a href="#sgs.Genetically_Related_Allelic_Disorder">Genetically Related Disorders</a>).</p></div></dd></dl></div></div></div></div></div></div><div id="sgs.Clinical_Characteristics"><h2 id="_sgs_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sgs.Clinical_Description"><h3>Clinical Description</h3><p>To date, 44 individuals have been identified with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SKI</i> [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>, <a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al 2017</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>, <a class="bk_pop" href="#sgs.REF.zhang.2019.936">Zhang et al 2019</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="sgs.T.select_features_of_shprintzengoldb" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.select_features_of_shprintzengoldb/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.select_features_of_shprintzengoldb_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"># of Persons w/Feature /<br /># Evaluated for Feature</th></tr></thead><tbody><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay / intellectual disability</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">41/44</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypotonia</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16/19</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Craniosynostosis <sup>1</sup></td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31/41</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dolichocephaly/scaphocephaly</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36/39</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypertelorism</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42/43</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Downslanting palpebral fissures</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38/41</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ocular proptosis</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34/42</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Malar flattening</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24/24</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">High narrow palate</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23/23</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Micrognathia</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36/40</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low-set, posteriorly rotated ears</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23/24</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Arachnodactyly</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43/44</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Camptodactyly</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24/38</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pectus deformity</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32/40</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Scoliosis</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29/39</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Joint hypermobility</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18/22</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Joint contractures</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32/36</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Foot malposition / talipes equinovarus / club foot / pes cavus</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23/31</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C1-C2 spine malformation</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7/10</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Aortic root dilatation</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14/41</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mitral valve prolapse / valvular anomalies</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12/38</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abdominal hernias</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14/23</td></tr><tr><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Minimal subcutaneous fat / marfanoid habitus</td><td headers="hd_h_sgs.T.select_features_of_shprintzengoldb_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9/20</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="sgs.TF.2.1"><p class="no_margin">Typically coronal, sagittal, or lambdoid sutures</p></div></dd></dl></div></div></div><p><b>Neurodevelopment.</b> Motor and cognitive milestones are delayed and intellectual disability is usually mild to moderate. To date, three individuals with Shprintzen-Goldberg syndrome (SGS) and a confirmed <i>SKI</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> were reported to have normal intelligence [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>, <a class="bk_pop" href="#sgs.REF.zhang.2019.936">Zhang et al 2019</a>].</p><p><b>Craniosynostosis</b> usually involves the coronal, sagittal, or lambdoid sutures. The sutures are fused at birth and craniosynostosis can usually be suspected from the abnormal skull shape. A single suture or multiple sutures may be involved [<a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>]. Information on individuals with SGS who underwent surgery for craniosynostosis in unavailable.</p><p>Characteristic craniofacial features include hypertelorism, downslanting palpebral fissures, ocular proptosis, high narrow palate, micrognathia, and low-set posteriorly rotated ears. Cleft palate was reported in three of 17 individuals with SGS [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>]. Broad/bifid uvula has been reported in two of 12 individuals [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>].</p><p><b>Musculoskeletal.</b> Arachnodactyly, camptodactyly, pectus deformities, and clubfeet are common features and are present at birth. Joint contractures are often present at birth or in the neonatal period, with the ankle joint most frequently affected [<a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al 2017</a>]. Joint hypermobility also occurs in individuals with SGS and is typically present from birth. Joint dislocation and instability reported by <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al [2019]</a> included involvement of the left patella, thumb, and foot and C1-C2 instability. <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al [2014]</a> reported subluxing patellae. Pes planus becomes evident later in childhood; one or both feet may be affected. Scoliosis may be severe [<a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>].</p><p><b>Cardiovascular.</b> Aortic root dilatation was present in three of 18 affected individuals reported by <a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al [2012]</a>. In the report of <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al [2012]</a>, however, eight of ten individuals with SGS and confirmed pathogenic variants in <i>SKI</i> had aortic root dilatation with or without mitral valve prolapse/incompetence. Surgery at age 16 years for aortic dilatation (aortic root dilatation with z score = 7.014) was reported in one individual with molecularly confirmed SGS [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>]. This individual also had vertebrobasilar and internal carotid tortuosity and a dilated pulmonary artery root. Among the affected individuals with molecularly confirmed SGS reported by <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al [2012]</a> one had arterial tortuosity and two had splenic artery aneurysm – one with spontaneous rupture.</p><p><b>Ocular.</b> Myopia was reported in ten of 19 individuals [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>]. Ectopia lentis has <b>not</b> been reported in the 16 individuals with SGS who were evaluated for this finding [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>].</p><p><b>Minimal subcutaneous fat</b> and/or <b>marfanoid habitus</b> was reported in nine of 20 individuals [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>].</p><p><b>Abdominal wall defects</b> were reported in 14 of 23 individuals [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>, <a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al 2017</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>].</p><p>
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<b>Other</b>
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</p><ul><li class="half_rhythm"><div>Dural ectasia (5/8 individuals) [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>]</div></li><li class="half_rhythm"><div>Chiari I malformation (2/3 individuals) [<a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>]</div></li><li class="half_rhythm"><div>Cryptorchidism (1/1 male) [<a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al 2017</a>]</div></li></ul></div><div id="sgs.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been identified.</p></div><div id="sgs.Penetrance"><h3>Penetrance</h3><p>Penetrance is unknown.</p></div><div id="sgs.Nomenclature"><h3>Nomenclature</h3><p>Goldberg-Shprintzen syndrome and Shprintzen-Goldberg omphalocele syndrome are separate syndromes, not related to SGS.</p><p>Other names that have been used to refer to SGS:</p><ul><li class="half_rhythm"><div>Craniosynostosis with arachnodactyly and abdominal hernias</div></li><li class="half_rhythm"><div>Marfanoid-craniosynostosis syndrome</div></li><li class="half_rhythm"><div>Shprintzen-Goldberg craniosynostosis syndrome</div></li><li class="half_rhythm"><div>Shprintzen-Goldberg marfanoid syndrome</div></li></ul><p>The term Furlong syndrome has been used to describe one individual with craniosynostosis, features of SGS, normal intelligence, and aortic enlargement. <a class="bk_pop" href="#sgs.REF.ad_s.2006.1047">Adès et al [2006]</a> reported on two individuals with a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> similar to Furlong syndrome. They had the same pathogenic <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant in <i>TGFBR1</i>, making a diagnosis of <a href="/books/n/gene/loeys-dietz/">Loeys-Dietz syndrome</a> type 1 most likely [B Loeys, personal communication]. In the absence of analysis for pathogenic variants in the original individual described as having Furlong syndrome, the existence of this as a separate entity remains unclear.</p></div><div id="sgs.Prevalence"><h3>Prevalence</h3><p>SGS is a rare disorder and the prevalence is unknown. A <i>SKI</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in 44 individuals with SGS to date.</p></div></div><div id="sgs.Genetically_Related_Allelic_Disorder"><h2 id="_sgs_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>SKI</i>.</p><p><b>1p36 <a class="def" href="/books/n/gene/glossary/def-item/deletion-syndrome/">deletion syndrome</a></b> (OMIM <a href="https://omim.org/entry/607872" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">607872</a>). <i>SKI</i> is located in the <a class="def" href="/books/n/gene/glossary/def-item/critical-region/">critical region</a> for the 1p36 deletion syndrome. It is currently unknown if SKI <a class="def" href="/books/n/gene/glossary/def-item/haploinsufficiency/">haploinsufficiency</a> contributes to the phenotypic features associated with proximal 1p36 deletions. One individual with a small 1p36 deletion that included <i>SKI</i>, <i>PRKCZ</i>, and <i>PEX10</i> had a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> that appeared to be distinct from SGS [<a class="bk_pop" href="#sgs.REF.zhu.2013.352">Zhu et al 2013</a>].</p></div><div id="sgs.Differential_Diagnosis"><h2 id="_sgs_Differential_Diagnosis_">Differential Diagnosis</h2><p><a href="/books/n/gene/loeys-dietz/"><b>Loeys-Dietz syndrome</b></a>
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<b>(LDS) and</b>
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<a href="/books/n/gene/marfan/"><b>Marfan syndrome</b></a>
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<b>(MFS).</b> The <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> of Shprintzen-Goldberg syndrome (SGS) is distinctive but shows some overlap with LDS and MFS (see <a href="/books/NBK1277/table/sgs.T.comparison_of_clinical_features_of/?report=objectonly" target="object" rid-ob="figobsgsTcomparisonofclinicalfeaturesof">Table 3</a>). Distinguishing features of SGS include the following:</p><ul><li class="half_rhythm"><div>Hypotonia and intellectual disability are rare findings in individuals with LDS and MFS but appear to be almost always present in those with SGS.</div></li><li class="half_rhythm"><div>Some of the distinctive radiographic findings in SGS are rarely found in individuals with either LDS or MFS. These include:</div><ul><li class="half_rhythm"><div>C1/C2 abnormality (in 7/10 individuals with SGS) [<a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>, <a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.saito.2017.1098">Saito et al 2017</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>];</div></li><li class="half_rhythm"><div>Thirteen pairs of ribs (1/1) [<a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>];</div></li><li class="half_rhythm"><div>Chiari I malformation (2/3 ) [<a class="bk_pop" href="#sgs.REF.au.2014.676">Au et al 2014</a>, <a class="bk_pop" href="#sgs.REF.odougherty.2019.1159">O'Dougherty et al 2019</a>].</div></li></ul></li><li class="half_rhythm"><div>Aortic root dilatation is less frequent in SGS than in LDS or MFS, but when present in individuals with SGS, it can be severe [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>]. One of the hallmarks of LDS is the occurrence of arterial tortuosity and aneurysms in arteries other than the aorta. Arterial tortuosity was found in two individuals with SGS; a further two individuals with SGS had splenic artery aneurysm [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al 2012</a>].</div></li></ul><div id="sgs.T.comparison_of_clinical_features_of" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Comparison of Clinical Features of SGS, <i>TGFBR1-/TGFBR2</i>-LDS, and MFS</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.comparison_of_clinical_features_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.comparison_of_clinical_features_of_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Feature</th><th id="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SGS</th><th id="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TGFBR1-</i>/<i>TGFBR2-</i><a href="/books/n/gene/loeys-dietz/">LDS</a> <sup>1</sup></th><th id="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/marfan/">MFS</a> <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ectopia lentis</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cleft palate / bifid uvula</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Widely spaced eyes</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniosynostosis</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tall stature</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arachnodactyly</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pectus deformity</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clubfoot</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Osteoarthritis</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Aortic root aneurysm</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arterial aneurysm</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arterial tortuosity</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Rare</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early dissection</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bicuspid aortic valve</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mitral valve insufficiency</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Striae</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">−</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">++</td></tr><tr><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dural ectasia</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td><td headers="hd_h_sgs.T.comparison_of_clinical_features_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">+</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>+ </dt><dd><div id="sgs.TF.3.1"><p class="no_margin">= feature is present; ++ = feature is more commonly present; +++ = feature is most commonly present; − = feature is absent; LDS = <a href="/books/n/gene/loeys-dietz/">Loeys-Dietz syndrome</a>; MFS = <a href="/books/n/gene/marfan/">Marfan syndrome</a>; SGS = Shprintzen-Goldberg syndrome</p></div></dd><dt>1. </dt><dd><div id="sgs.TF.3.2"><p class="no_margin">Approximately 75%-85% of Loeys-Dietz syndrome is attributed to pathogenic variants in <i>TGFBR2</i> or <i>TGFBR1</i>. LDS is also known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic variants in <i>SMAD2</i>, <i>SMAD3</i>, <i>TGFB2</i>, and <i>TGFB3</i>. LDS is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div></dd><dt>2. </dt><dd><div id="sgs.TF.3.3"><p class="no_margin">Marfan syndrome is caused by pathogenic variants in <i>FBN1</i> and inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div></dd></dl></div></div></div><p>
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<b>Other disorders</b>
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</p><div id="sgs.T.disorders_of_interest_in_the_diffe" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Disorders of Interest in the Differential Diagnosis of Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.disorders_of_interest_in_the_diffe/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.disorders_of_interest_in_the_diffe_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of DiffDx Disorder</th></tr><tr><th headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4" id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/SGS</th><th headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4" id="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from SGS</th></tr></thead><tbody><tr><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FBN2</i>
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</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cca/">Congenital contractural arachnodactyly</a>
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</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dolichostenomelia, arachnodactyly</div></li><li class="half_rhythm"><div>Kyphosis/scoliosis <sup>1</sup></div></li><li class="half_rhythm"><div>Aortic dilatation (occasionally present)</div></li></ul>
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</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most persons w/CCA have "crumpled" ears that present as a folded upper helix of the external ear.</td></tr><tr><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FLNA</i>
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</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontometaphyseal dysplasia & Melnick-Needles syndrome (See <a href="/books/n/gene/opd/">Otopalatodigital Spectrum Disorders</a>.)</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tall, square-shaped vertebrae; bowed tibiae; occasionally, fusion of upper cervical vertebrae</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presence of ID & craniosynostosis in SGS usually distinguishes it from MNS or FMD.</td></tr><tr><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>B3GAT3</i>
|
||
</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>B3GAT3</i>-related disorder <sup>2</sup></td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniosynostosis, midface hypoplasia, kyphoscoliosis, joint contractures, long fingers, foot deformity, cardiovascular abnormalities</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presence of multiple neonatal fractures, hypoplasia of the nasal bones, femoral bowing, & overlapping fingers helps distinguish this disorder from SGS.</td></tr><tr><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>HNRNPK</i>
|
||
</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/au-kline/">Au-Kline syndrome</a>
|
||
</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Aortic dilatation</div></li><li class="half_rhythm"><div>Sagittal craniosynostosis, shallow orbits, palate abnormalities, &/or bifid uvula</div></li><li class="half_rhythm"><div>ID (mild to moderate)</div></li><li class="half_rhythm"><div>Skeletal anomalies</div></li></ul>
|
||
</td><td headers="hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_1_4 hd_h_sgs.T.disorders_of_interest_in_the_diffe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Marfanoid body habitus</div></li><li class="half_rhythm"><div>Arachnodactyly & camptodactyly</div></li><li class="half_rhythm"><div>Congenital heart disease</div></li><li class="half_rhythm"><div>Hydronephrosis</div></li><li class="half_rhythm"><div>Hearing loss</div></li><li class="half_rhythm"><div>Seizures</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>; CCA = <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> contractural arachnodactyly; DiffDx = differential diagnosis; FMD = frontometaphyseal dysplasia; ID = intellectual disability; MNS = Melnick-Needles syndrome; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; SGS = Shprintzen-Goldberg syndrome; 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="sgs.TF.4.1"><p class="no_margin">Kyphosis/scoliosis in ~50% of individuals with CCA (begins as early as infancy, is progressive, & causes the greatest morbidity in CCA)</p></div></dd><dt>2. </dt><dd><div id="sgs.TF.4.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#sgs.REF.yauy.2018.269">Yauy et al [2018]</a>
|
||
</p></div></dd></dl></div></div></div></div><div id="sgs.Management"><h2 id="_sgs_Management_">Management</h2><div id="sgs.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with Shprintzen-Goldberg syndrome (SGS), the evaluations summarized in <a href="/books/NBK1277/table/sgs.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobsgsTrecommendedevaluationsfollowing">Table 5</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="sgs.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.recommended_evaluations_following_lrgtbl__"><table><thead><tr><th id="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurodevelopment</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for developmental disabilities</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral for early intervention services; consider referral to neurodevelopmental specialist.</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Craniofacial</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Physical exam</div></li><li class="half_rhythm"><div>Head CT to evaluate sutures if craniosynostosis suspected</div></li></ul>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To identify cleft palate & craniosynostosis</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_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_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to orthopedist &/or radiographs as indicated</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for C1/C2 abnormality, scoliosis, severe pectus deformity, abnormal joint mobility, & foot malposition</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for aortic root dilatation</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider MRA or CT scan w/3D reconstruction from head to pelvis.</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To identify arterial aneurysms & arterial tortuosity throughout the arterial tree</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmology</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam by ophthalmologist w/expertise in connective tissue disorders</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for myopia & complications of proptosis</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurology</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for Chiari I malformation</td></tr><tr><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_sgs.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></div><div id="sgs.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management of SGS is best conducted through the coordinated input of a multidisciplinary team of specialists including a clinical geneticist, cardiologist, ophthalmologist, orthopedist, cardiothoracic surgeon, and craniofacial team.</p><div id="sgs.T.treatment_of_manifestations_in_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.treatment_of_manifestations_in_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_sgs.T.treatment_of_manifestations_in_ind_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_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early intervention services</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider consultation w/developmental pediatrician or neurodevelopmental specialist.</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Craniosynostosis</b>
|
||
<br />
|
||
<b>& cleft palate</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt by craniofacial team</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment as in other disorders w/these manifestations</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cervical spine</b>
|
||
<br />
|
||
<b>instability</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical fixation may be necessary.</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Scoliosis</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Pectus excavatum</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May be severe; rarely, surgical correction indicated for medical reasons</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Joint contractures</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physiotherapy may help ↑ mobility.</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Clubfoot deformity</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May require surgical correction</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Aortic dilatation</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment w/beta-adrenergic blockers or other medications per cardiologist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Should be considered in order to ↓ hemodynamic stress</td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Aneurysms</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical intervention may be indicated; per vascular surgeon.</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Myopia</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per ophthalmologist</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Abdominal hernia</b>
|
||
</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair may be indicated.</td><td headers="hd_h_sgs.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DD = developmental delay</p></div></dd></dl></div></div></div></div><div id="sgs.Prevention_of_Secondary_Complication"><h3>Prevention of Secondary Complications</h3><p>For individuals with cardiac complications, subacute bacterial endocarditis prophylaxis is recommended for dental work or other procedures expected to contaminate the bloodstream with bacteria.</p></div><div id="sgs.Surveillance"><h3>Surveillance</h3><div id="sgs.T.recommended_surveillance_for_indiv" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Shprintzen-Goldberg Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.T.recommended_surveillance_for_indiv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.T.recommended_surveillance_for_indiv_lrgtbl__"><table><thead><tr><th id="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sgs.T.recommended_surveillance_for_indiv_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_sgs.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurodevelopment</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_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_sgs.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cervical spine eval</div></li><li class="half_rhythm"><div>Clinical eval for scoliosis</div></li></ul>
|
||
</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per orthopedist</td></tr><tr><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiology</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Imaging per cardiologist to screen for aortopathy, mitral valve anomalies, & aneurysms</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per cardiologist</td></tr><tr><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vision issues</b>
|
||
</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam</td><td headers="hd_h_sgs.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per ophthalmologist</td></tr></tbody></table></div></div></div><div id="sgs.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>The following should be avoided:</p><ul><li class="half_rhythm"><div>Contact sports, which may lead to catastrophic complications in those with cardiovascular issues or cervical spine anomalies/instability</div></li><li class="half_rhythm"><div>Agents that stimulate the cardiovascular system, including routine use of decongestants</div></li><li class="half_rhythm"><div>Activities that cause joint pain or injury</div></li></ul></div><div id="sgs.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#sgs.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="sgs.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="sgs.Genetic_Counseling"><h2 id="_sgs_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="sgs.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Shprintzen-Goldberg syndrome (SGS), caused by a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SKI</i>, is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div><div id="sgs.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>To date, most probands diagnosed with SGS represent <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (i.e., a single occurrence in a family) and are assumed to have the disorder as a result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Rarely, an individual diagnosed with SGS has the disorder as the result of an inherited <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Recurrence of SGS was reported in a three-generation family with SGS [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>] (family 3).</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> with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> found in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, possible explanations include a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> pathogenic variant in the proband or <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a parent. Parental germline mosaicism could explain <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> recurrence with unaffected parents. See <a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al [2012]</a> (family 4: individuals 8, 9, 10), <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al [2015]</a> (individuals 10, 11).</div></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with SGS may appear to be negative because of a milder phenotypic presentation in an affected family member. Therefore, an apparently negative family history cannot be confirmed until appropriate clinical evaluation and/or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> has been performed.</div></li><li class="half_rhythm"><div>If the parent is the individual in whom the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> first occurred, the parent may have <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> for the variant and may be mildly/minimally affected.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs is 50%. Multigenerational <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> recurrence of SGS is rare but has been reported [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>].</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a known <i>SKI</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is slightly greater than that of the general population because of the possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>, <a class="bk_pop" href="#sgs.REF.schepers.2015.224">Schepers et al 2015</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>SKI</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> but are clinically unaffected, sibs are still presumed to be at increased risk for SGS because of the possibility of reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> in a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> parent or parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with SGS has a 50% chance of inheriting the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and having SGS.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents: if a parent has the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, members of the parent's family may be at risk.</p></div><div id="sgs.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p><b>Considerations in families with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</b> When neither parent of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> condition has the pathogenic variant identified in the proband or clinical evidence of the disorder, the pathogenic variant is likely <i>de novo</i>. However, non-medical explanations including <a class="def" href="/books/n/gene/glossary/def-item/alternate-paternity/">alternate paternity</a> or maternity (e.g., with assisted reproduction) and undisclosed adoption could also be explored.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul></div><div id="sgs.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SKI</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="sgs.Resources"><h2 id="_sgs_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>Children's Craniofacial Association</b>
|
||
</div><div><b>Phone:</b> 800-535-3643</div><div><b>Email:</b> contactCCA@ccakids.com</div><div>
|
||
<a href="https://ccakids.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ccakids.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
|
||
</div><div><b>Phone:</b> 800-352-9424</div><div>
|
||
<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Craniosynostosis-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Craniosynostosis</a>
|
||
</div></li></ul>
|
||
</div><div id="sgs.Molecular_Genetics"><h2 id="_sgs_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="sgs.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Shprintzen-Goldberg Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1277/table/sgs.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sgs.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sgs.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sgs.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sgs.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sgs.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sgs.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/6497" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>SKI</i>
|
||
</a>
|
||
</td><td headers="hd_b_sgs.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=6497" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1p36<wbr style="display:inline-block"></wbr>.33-p36.32</a>
|
||
</td><td headers="hd_b_sgs.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P12755" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Ski oncogene</a>
|
||
</td><td headers="hd_b_sgs.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SKI" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SKI</a>
|
||
</td><td headers="hd_b_sgs.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SKI[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SKI</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="sgs.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="sgs.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Shprintzen-Goldberg Syndrome (<a href="/omim/164780,182212" 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/NBK1277/table/sgs.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sgs.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/164780" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">164780</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SKI PROTOONCOGENE; SKI</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/182212" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">182212</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME; SGS</td></tr></tbody></table></div></div><div id="sgs.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>SKI</i> encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene, which functions as a repressor of TGF-β signaling. The SKI family of proteins negatively regulate SMAD-dependent TGF-β signaling by preventing nuclear <a class="def" href="/books/n/gene/glossary/def-item/translocation/">translocation</a> of the receptor-activated SMAD (R-SMAD)-SMAD4 complex and inhibiting TGF-β target <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> output by competing with p300/CBP for SMAD binding and recruiting transcriptional repressor proteins, such as mSin3A and HDAC1.</p><p>The SKI oncogene is present in all cells, and is commonly active during development. It has a 728 amino-acid sequence with multiple domains and is expressed both inside and outside the cell. The different domains have different functions, including interaction with SMAD proteins.</p><p><b>Mechanism of disease causation.</b> Cultured dermal fibroblasts from individuals with molecularly confirmed SGS showed enhanced activation of TGF-β signaling cascades and higher expression of TGF-β-responsive genes relative to control cells. <a class="bk_pop" href="#sgs.REF.doyle.2012.1249">Doyle et al [2012]</a> concluded that increased TBF-β signaling is the mechanism underlying SGS.</p><p>TGF-β signaling is crucial to normal development and maintenance of various organs, including the vasculature. <i>SKI</i> exerts a negative regulatory effect on TGF-β signaling by interacting with other cellular partners, such as SMAD proteins and transcriptional co-regulators. All pathogenic variants of <i>SKI</i> are located in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 1 and cluster into two domains: the R-SMAD binding <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> and daschund homology domain (DHD). Zebrafish studies indicate that SKI plays crucial roles in aortic morphogenesis and homeostasis, and that aortic aneurysm formation in individujals with SGS is a result of increased TGF-β signaling, similar to aortopathies in <a href="/books/n/gene/marfan/">Marfan syndrome</a> and <a href="/books/n/gene/loeys-dietz/">Loeys-Dietz syndrome</a> [<a class="bk_pop" href="#sgs.REF.takeda.2018.2125">Takeda et al 2018</a>]. For a review of the regulatory effects of transcriptional cofactors Ski (Sloan-Kettering Institute) and SnoN (Ski novel) on the TGF-β signaling pathway in health and disease, see <a class="bk_pop" href="#sgs.REF.tecalcocruz.2018.15">Tecalco-Cruz et al [2018]</a>.</p><p><b><i>SKI</i>-specific laboratory technical considerations.</b> The majority of pathogenic variants are <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> and are located in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 1 of <i>SKI</i> [<a class="bk_pop" href="#sgs.REF.carmignac.2012.950">Carmignac et al 2012</a>]. A mutational <a class="def" href="/books/n/gene/glossary/def-item/hot-spot/">hot spot</a> has been identified in the R-SMAD <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> of exon 1 with 24 (73%) of 33 unrelated individuals having a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> within a stretch of five residues (from Ser31 to Pro35). A smaller number of individuals with pathogenic variants in the DHD domain have been reported, suggesting a second mutational hotspot in this domain [<a class="bk_pop" href="#sgs.REF.zhang.2019.936">Zhang et al 2019</a>].</p></div></div><div id="sgs.Chapter_Notes"><h2 id="_sgs_Chapter_Notes_">Chapter Notes</h2><div id="sgs.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>9 April 2020 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>13 June 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>16 November 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>13 January 2006 (me) Review posted live</div></li><li class="half_rhythm"><div>2 December 2004 (mtg) Original submission</div></li></ul></div></div><div id="sgs.References"><h2 id="_sgs_References_">References</h2><div id="sgs.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.ad_s.2006.1047">Adès LC, Sullivan K, Biggin A, Haan EA, Brett M, Holman KJ, Dixon J, Robertson S, Holmes AD, Rogers J, Bennetts B. FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. <span><span class="ref-journal">Am J Med Genet A. </span>2006;<span class="ref-vol">140</span>:1047–58.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16596670" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16596670</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.au.2014.676">Au PY, Racher HE, Graham JM Jr, Kramer N, Lowry RB, Parboosingh JS, Innes AM, et al. De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and clinical review. <span><span class="ref-journal">Am J Med Genet A. </span>2014;<span class="ref-vol">164A</span>:676–84.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24357594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24357594</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.carmignac.2012.950">Carmignac V, Thevenon J, Adès L, Callewaert B, Julia S, Thauvin-Robinet C, Gueneau L, Courcet JB, Lopez E, Holman K, Renard M, Plauchu H, Plessis G, De Backer J, Child A, Arno G, Duplomb L, Callier P, Aral B, Vabres P, Gigot N, Arbustini E, Grasso M, Robinson PN, Goizet C, Baumann C, Di Rocco M, Sanchez Del Pozo J, Huet F, Jondeau G, Collod-Beroud G, Beroud C, Amiel J, Cormier-Daire V, Rivière JB, Boileau C, De Paepe A, Faivre L. In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2012;<span class="ref-vol">91</span>:950–7.</span> [<a href="/pmc/articles/PMC3487125/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3487125</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23103230" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23103230</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.doyle.2012.1249">Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destrée A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, Loeys BL, Dietz HC. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. <span><span class="ref-journal">Nat Genet. </span>2012;<span class="ref-vol">44</span>:1249–54.</span> [<a href="/pmc/articles/PMC3545695/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3545695</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23023332" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23023332</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.odougherty.2019.1159">O'Dougherty GR, Fulkerson DH, Kern M, Haldar K, Calhoun B. Complications of insufficient dura and blood loss during surgical intervention in Shprintzen-Goldberg syndrome: a case report. <span><span class="ref-journal">Am J Case Rep. </span>2019;<span class="ref-vol">20</span>:1159–69.</span> [<a href="/pmc/articles/PMC6698069/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6698069</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31391415" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31391415</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.saito.2017.1098">Saito T, Nakane T, Yagasaki H, Naito A, Sugita K. Shprintzen-Goldberg syndrome associated with first cervical vertebra defects. <span><span class="ref-journal">Pediatr Int. </span>2017;<span class="ref-vol">59</span>:1098–100.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28857439" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28857439</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.schepers.2015.224">Schepers D, Doyle AJ, Oswald G, Sparks E, Myers L, Willems PJ, Mansour S, Simpson MA, Frysira H, Maat-Kievit A, Van Minkelen R, Hoogeboom JM, Mortier GR, Titheradge H, Brueton L, Starr L, Stark Z, Ockeloen C, Lourenco CM, Blair E, Hobson E, Hurst J, Maystadt I, Destrée A, Girisha KM, Miller M, Dietz HC, Loeys B, Van Laer L. The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen-Goldberg syndrome. <span><span class="ref-journal">Eur J Hum Genet. </span>2015;<span class="ref-vol">23</span>:224–8.</span> [<a href="/pmc/articles/PMC4297897/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4297897</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24736733" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24736733</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.takeda.2018.2125">Takeda N, Hara H, Fujiwara T, Kanaya T, Maemura S, Komuro I. TGF-β signaling-related genes and thoracic aortic aneurysms and dissections. <span><span class="ref-journal">Int J Mol Sci. </span>2018;<span class="ref-vol">19</span>:2125.</span> [<a href="/pmc/articles/PMC6073540/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6073540</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30037098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30037098</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.tecalcocruz.2018.15">Tecalco-Cruz AC, Ríos-López DG, Vázquez-Victorio G, Rosales-Alvarez RE, Macías-Silva M. Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease. <span><span class="ref-journal">Signal Transduct Target Ther. </span>2018;<span class="ref-vol">3</span>:15.</span> [<a href="/pmc/articles/PMC5992185/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5992185</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29892481" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29892481</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.yauy.2018.269">Yauy K, Tran Mau-Them F, Willems M, Coubes C, Blanchet P, Herlin C, Taleb Arrada I, Sanchez E, Faure JM, Le Gac MP, Prodhomme O, Boland A, Meyer V, Rivière JB, Duffourd Y, Deleuze JF, Guignard T, Captier G, Barat-Houari M, Genevieve D. B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation. <span><span class="ref-journal">Genet Med. </span>2018;<span class="ref-vol">20</span>:269–74.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28771243" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28771243</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.zhang.2019.936">Zhang L, Xu X, Sun K, Sun J, Wang Y, Liu Y, Yang N, Tao C, Cai B, Shi G, Zhang F, Shi J. A de novo mutation in DHD domain of SKI causing spina bifida with no craniofacial malformation or intellectual disability. <span><span class="ref-journal">Am J Med Genet A. </span>2019;<span class="ref-vol">179</span>:936–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30883014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30883014</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="sgs.REF.zhu.2013.352">Zhu X, Zhang Y, Wang J, Yang JF, Yang YF, Tan ZP. 576 kb deletion in 1p36.33-p36.32 containing SKI is associated with limb malformation, congenital heart disease and epilepsy. <span><span class="ref-journal">Gene. </span>2013;<span class="ref-vol">528</span>:352–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23892090" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23892090</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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