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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Osteopathia Striata with Cranial Sclerosis" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/03/30" /><meta name="citation_author" content="Russell Gear" /><meta name="citation_author" content="Ravi Savarirayan" /><meta name="citation_pmid" content="33856753" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK569515/" /><meta name="citation_keywords" content="Horan-Beighton Syndrome" /><meta name="citation_keywords" content="OS-CS" /><meta name="citation_keywords" content="AMER1-Related Osteopathia Striata with Cranial Sclerosis" /><meta name="citation_keywords" content="Horan-Beighton Syndrome" /><meta name="citation_keywords" content="OS-CS" /><meta name="citation_keywords" content="APC membrane recruitment protein 1" /><meta name="citation_keywords" content="AMER1" /><meta name="citation_keywords" content="Osteopathia Striata with Cranial Sclerosis" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Osteopathia Striata with Cranial Sclerosis" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Russell Gear" /><meta name="DC.Contributor" content="Ravi Savarirayan" /><meta name="DC.Date" content="2023/03/30" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK569515/" /><meta name="description" content="Most females with osteopathia striata with cranial sclerosis (OS-CS) present with macrocephaly and characteristic facial features (frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge, and prominent jaw). 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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="#__NBK569515_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK569515_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/og-dysp/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/pacs1-ndd/" 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="_NBK569515_"><span class="title" itemprop="name">Osteopathia Striata with Cranial Sclerosis</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Horan-Beighton Syndrome, OS-CS, <i>AMER1</i>-Related Osteopathia Striata with Cranial Sclerosis</div><p class="contrib-group"><span itemprop="author">Russell Gear</span>, MBChB and <span itemprop="author">Ravi Savarirayan</span>, MBBS, MD, FRACP, ARCPA (Hon).</p><a data-jig="ncbitoggler" href="#__NBK569515_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK569515_ai__"><div class="contrib half_rhythm"><span itemprop="author">Russell Gear</span>, MBChB<div class="affiliation small">Victorian Clinical Genetics Services<br />Murdoch Children's Research Institute<br />Parkville, Victoria, Australia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamtoh@raegllessur" class="oemail">moc.liamtoh@raegllessur</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ravi Savarirayan</span>, MBBS, MD, FRACP, ARCPA (Hon)<div class="affiliation small">Victorian Clinical Genetics Services<br />Murdoch Children's Research Institute<br />Parkville, Victoria, Australia</div><div class="affiliation small">University of Melbourne<br />Melbourne, Australia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ua.ude.ircm@nayariravas.ivar" class="oemail">ua.ude.ircm@nayariravas.ivar</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">April 15, 2021</span>; Last Revision: <span itemprop="dateModified">March 30, 2023</span>.</p><p><em>Estimated reading time: 26 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="os-cs.Summary" itemprop="description"><h2 id="_os-cs_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Most females with osteopathia striata with cranial sclerosis (OS-CS) present with macrocephaly and characteristic facial features (frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge, and prominent jaw). Approximately half have associated features including orofacial clefting and hearing loss, and a minority have some degree of developmental delay (usually mild). Radiographic findings of cranial sclerosis, sclerosis of long bones, and metaphyseal striations (in combination with macrocephaly) can be considered pathognomonic.</p><p>Males can present with a mild or severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Mildly affected males have clinical features similar to affected females, including macrocephaly, characteristic facial features, orofacial clefting, hearing loss, and mild-to-moderate learning delays. Mildly affected males are more likely than females to have <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> or musculoskeletal anomalies. Radiographic findings include cranial sclerosis and sclerosis of the long bones; Metaphyseal striations are more common in males who are mosaic for an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p><p>The severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> manifests in males as a multiple-malformation syndrome, lethal in mid-to-late gestation, or in the neonatal period. Congenital malformations include skeletal defects (e.g., polysyndactyly, absent or hypoplastic fibulae), <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease, and brain, genitourinary, and gastrointestinal anomalies. Macrocephaly is not always present and longitudinal metaphyseal striations have not been observed in severely affected males, except for those who are mosaic for the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of OS-CS is established in a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic features and 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>AMER1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. The diagnosis of OS-CS is established in a male proband with characteristic features and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> pathogenic variant in <i>AMER1</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment:</i> Scoliosis management per orthopedic surgeon; physiotherapy may be helpful for joint contractures; management of oral facial clefts per otolaryngologist; hearing loss is managed by audiology, speech and language therapy, and otolaryngology; vision loss management per ophthalmologist and neurosurgery for nerve compression as indicated; early intervention services and special education as indicated; standard treatments for cardiac, genitourinary, and gastrointestinal anomalies and Wilms tumor or other malignancy.</p><p><i>Surveillance:</i> Annual clinical assessment for skeletal manifestations such as scoliosis, joint contractures, stress fractures, and persistent bone pain. Annual audiology and ophthalmology evaluations for evidence of cranial nerve compression due to sclerotic bone disorder. Consider abdominal ultrasound every three months until age seven years to screen for Wilms tumor.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>OS-CS is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner. The risk to sibs of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> depends on the genetic status of the mother. The risk to sibs of a female proband depends on the genetic status of the mother and the father. If the mother of the proband has an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting it in each pregnancy is 50%. If the father of the proband has an <i>AMER1</i> pathogenic variant, it should be presumed he will transmit the <i>AMER1</i> pathogenic variant to all his daughters and none of his sons (to date, paternal transmission has only been reported in mosaic fathers). Females who inherit an <i>AMER1</i> pathogenic variant will be heterozygotes and will have variable manifestations of OS-CS. Males who inherit a pathogenic variant will be hemizygotes and will have variable manifestations ranging from mid-late gestation and neonatal lethality to the mild <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Once the <i>AMER1</i> pathogenic variant is 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></div></div><div id="os-cs.Diagnosis"><h2 id="_os-cs_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for osteopathia striata with cranial sclerosis (OS-CS) have been published, however the combination of macrocephaly, cranial sclerosis, and longitudinal metaphyseal striations of the long bones are considered highly characteristic of this condition.</p><div id="os-cs.Suggestive_Findings"><h3>Suggestive Findings</h3><p>OS-CS <b>should be suspected</b> in individuals with the following clinical and radiographic findings.</p><div id="os-cs.Females_and_Mosaic_andor_Mildly_Af"><h4>Females and Mosaic and/or Mildly Affected Males</h4><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Characteristic facial features (e.g., frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge, prominent jaw)</div></li><li class="half_rhythm"><div>Macrocephaly and stature short for mid-parental height</div></li><li class="half_rhythm"><div>Orofacial clefting</div></li><li class="half_rhythm"><div>Hearing loss (conductive and sensorineural) and progressive hearing loss</div></li><li class="half_rhythm"><div>Poor or reduced vision</div></li><li class="half_rhythm"><div>Normal intellect or mild developmental delays</div></li></ul><p>
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<b>Radiographic findings</b>
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</p><ul><li class="half_rhythm"><div>Sclerosis of the cranium and skull base</div></li><li class="half_rhythm"><div>Sclerosis of lamellar and trabecular bones</div></li><li class="half_rhythm"><div>Metaphyseal, longitudinal striations of the long bones and pelvis (Note: Metaphyseal striations are typically absent in mildly affected constitutional males but present in mosaic males.)</div></li><li class="half_rhythm"><div>Fibular aplasia or hypoplasia</div></li><li class="half_rhythm"><div>Small exostoses</div></li></ul></div><div id="os-cs.Severely_Affected_Males"><h4>Severely Affected Males</h4><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Fetal or neonatal death</div></li><li class="half_rhythm"><div>Macrocephaly (50%)</div></li><li class="half_rhythm"><div>Orofacial clefting (cleft palate or cleft lip and palate)</div></li><li class="half_rhythm"><div>Facial features (frontal bossing, hypertelorism, depressed nasal bridge, and micrognathia)</div></li><li class="half_rhythm"><div>Multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> malformations:</div><ul><li class="half_rhythm"><div>Skeletal anomalies (polysyndactyly, talipes)</div></li><li class="half_rhythm"><div>Genitourinary anomalies (echogenic or enlarged kidneys, nephrogenic rests)</div></li><li class="half_rhythm"><div>Gastrointestinal anomalies (omphalocele, intestinal malrotation)</div></li><li class="half_rhythm"><div>Congenital heart disease (hypoplastic left or right heart, septal defects, patent ductus arteriosus)</div></li><li class="half_rhythm"><div>Brain anomalies (ventriculomegaly, abnormal corpus callosum)</div></li></ul></li></ul><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div>Cranial sclerosis</div></li><li class="half_rhythm"><div>Sclerosis of pelvis and long bones</div></li><li class="half_rhythm"><div>Bilateral absent or hypoplastic fibulae</div></li></ul></div></div><div id="os-cs.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The diagnosis of OS-CS <b>is established</b> in a female proband with <a href="#os-cs.Suggestive_Findings">suggestive findings</a> and can be confirmed 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>AMER1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK569515/table/os-cs.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figoboscsTmoleculargenetictestingusedi">Table 1</a>).</p><p><b>Male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The diagnosis of OS-CS <b>is established</b> in a male proband with <a href="#os-cs.Suggestive_Findings">suggestive findings</a> and can be confirmed with a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>AMER1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK569515/table/os-cs.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figoboscsTmoleculargenetictestingusedi">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bk_pop" href="#os-cs.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> or <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>AMER1</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 <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b>, <b><a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> analysis</b>, <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>, and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</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>AMER1</i> is performed first to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Chromosomal microarray analysis (CMA)</b> uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>AMER1</i>) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>AMER1</i> and other genes of interest (see <a href="#os-cs.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm">When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other skeletal dysplasias, <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div id="os-cs.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Osteopathia Striata with Cranial Sclerosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.molecular_genetic_testing_used_i_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_os-cs.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_os-cs.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_os-cs.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AMER1</i>
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</td><td headers="hd_h_os-cs.T.molecular_genetic_testing_used_i_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_os-cs.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~75% <sup>4</sup></td></tr><tr><td headers="hd_h_os-cs.T.molecular_genetic_testing_used_i_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_os-cs.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~25% <sup>4</sup></td></tr><tr><td headers="hd_h_os-cs.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">CMA <sup>6</sup></td><td headers="hd_h_os-cs.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 7.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="os-cs.TF.1.1"><p class="no_margin">See <a href="/books/NBK569515/#os-cs.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="os-cs.TF.1.2"><p class="no_margin">See <a href="#os-cs.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="os-cs.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="os-cs.TF.1.4"><p class="no_margin">Review of approximately 90 pathogenic variants in the published literature [Author, personal observation], correlation with smaller published case series [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>], and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bk_pop" href="#os-cs.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="os-cs.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="os-cs.TF.1.6"><p class="no_margin">Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>AMER1</i>) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>. The ability to determine the size of the <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a>/<a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> depends on the type of microarray used and the density of probes in the Xq11.2 region. CMA designs in current clinical use target the Xq11.2 region.</p></div></dd><dt>7. </dt><dd><div id="os-cs.TF.1.7"><p class="no_margin">Several contiguous deletions including <i>AMER1</i> have been reported in individuals with features of OS-CS [<a class="bk_pop" href="#os-cs.REF.ch_nier.2012.2946">Chénier et al 2012</a>, <a class="bk_pop" href="#os-cs.REF.herman.2013.594">Herman et al 2013</a>, <a class="bk_pop" href="#os-cs.REF.holman.2013.251">Holman et al 2013</a>]. Contiguous <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions that include <i>AMER1</i> and neighboring genes <i>ARHGEF9</i> and <i>MTMR8</i> appear to cause OS-CS with intellectual disability in females. Deletions including <i>AMER1</i> and <i>ASB12</i> only are not reported to be associated with intellectual disability [<a class="bk_pop" href="#os-cs.REF.holman.2013.251">Holman et al 2013</a>].</p></div></dd></dl></div></div></div></div></div><div id="os-cs.Clinical_Characteristics"><h2 id="_os-cs_Clinical_Characteristics_">Clinical Characteristics</h2><div id="os-cs.Clinical_Description"><h3>Clinical Description</h3><p>To date, approximately 90 individuals with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>AMER1</i> have been reported in the medical literature [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>; <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>; Author, personal observation]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="os-cs.T.osteopathia_striata_with_cranial" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Osteopathia Striata with Cranial Sclerosis: Frequency of Select Features in Females and Mildly Affected Males</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.osteopathia_striata_with_cranial/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.osteopathia_striata_with_cranial_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature <sup>1</sup></th><th id="hd_h_os-cs.T.osteopathia_striata_with_cranial_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_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cranial sclerosis</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sclerosis of long bones</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Metaphyseal striations</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~95%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In females & mosaic males; not seen in constitutional males</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Characteristic facial features</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~90%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frontal bossing, hypertelorism, epicanthal folds, depressed nasal bridge</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Macrocephaly</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~80%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absolute or relative macrocephaly</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orofacial clefting</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~50%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cleft palate or cleft lip and palate</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing loss</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~50%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Conductive &/or sensorineural</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild developmental delays</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~30%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe developmental delay is rare.</td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital heart disease</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~25%</td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wilms tumor <sup>2</sup></td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~5% <sup>3</sup></td><td headers="hd_h_os-cs.T.osteopathia_striata_with_cranial_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Additional malignancies reported: hepatoblastoma, adult-onset colorectal cancer, adult-onset ovarian cancer</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="os-cs.TF.2.1"><p class="no_margin">Review of approximately 90 individuals reported with OS-CS and an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a></p></div></dd><dt>2. </dt><dd><div id="os-cs.TF.2.2"><p class="no_margin">Association with Wilms tumor (and possibly other cancers) is an emerging feature and a significant departure from what was previously understood about the disorder.</p></div></dd><dt>3. </dt><dd><div id="os-cs.TF.2.3"><p class="no_margin">Extrapolated from recently published data [<a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>]</p></div></dd></dl></div></div></div><div id="os-cs.Affected_Females"><h4>Affected Females</h4><p>Most females with osteopathia striata with cranial sclerosis (OS-CS) present with macrocephaly and characteristic facial features (frontal bossing, hypertelorism, epicanthal folds, and a depressed nasal bridge). Approximately half have associated features including orofacial clefting and hearing loss, and a minority have some degree of developmental delay (usually mild). Radiographic findings of cranial sclerosis, sclerosis of long bones, and metaphyseal striations (in combination with macrocephaly) can be considered pathognomonic.</p><ul><li class="half_rhythm"><div><b>Cranial sclerosis.</b> Observed on radiographs of the skull, most notably in the vault. It can be present at birth, and is typically progressive.</div></li><li class="half_rhythm"><div><b>Sclerosis of the pelvis and long bones.</b> Best observed on radiographs of the pelvis and diaphyses of the femora and humeri. It can be present at birth, and is typically progressive.</div></li><li class="half_rhythm"><div><b>Metaphyseal striations.</b> Best observed on radiographs of the pelvis, proximal and distal femora, proximal tibiae, and humeri. It can be present antenatally, but usually develops during childhood.</div></li><li class="half_rhythm"><div><b>Characteristic facial features.</b> Most commonly include frontal bossing, hypertelorism, epicanthal folds, and a depressed nasal bridge. These features can be present at birth, and typically become more exaggerated with age, particularly frontal bossing.</div></li><li class="half_rhythm"><div><b>Macrocephaly</b> is usually of postnatal onset and is associated with cranial sclerosis. It is usually absolute (>+2.5 SD), but can be relative to height or weight.</div></li><li class="half_rhythm"><div><b>Stature.</b> Unlike in many other skeletal dysplasias, short stature is not commonly associated with OS-CS.</div></li><li class="half_rhythm"><div><b>Orofacial clefting.</b> Typically cleft hard palate; bifid uvula has also been observed.</div></li><li class="half_rhythm"><div><b>Hearing loss.</b> Both conductive and sensorineural hearing loss have been observed; hearing loss occurs in approximately 50% of females [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Cranial nerve palsies.</b> Rarely, compression of the optic nerve due to bony sclerosis can lead to vision loss, and facial palsies have been reported. This can be progressive, and typically occurs in late adolescence and early adulthood.</div></li><li class="half_rhythm"><div><b>Cognition.</b> Most females with OS-CS have normal intellect and a minority (30%) have mild learning delays [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>]. One female with severe learning delays has been reported [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>].</div></li><li class="half_rhythm"><div><b>Congenital heart disease.</b> Approximately 25% of females with OS-CS have a structural heart defect [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2010.82">Perdu et al 2010</a>]. Atrial septal defects, ventricular septal defects, and patent ductus arteriosus are the most commonly described structural anomalies.</div></li><li class="half_rhythm"><div><b>Association with cancer.</b> An association of OS-CS with cancer is emerging in the literature. To date, cancer has only been reported in females with OS-CS, including four instances of pediatric-onset <b>Wilms tumor</b>: one female with bilateral tumors [<a class="bk_pop" href="#os-cs.REF.sperotto.2017.674">Sperotto et al 2017</a>, <a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>], one with a pediatric-onset hepatoblastoma [<a class="bk_pop" href="#os-cs.REF.fujita.2014.998">Fujita et al 2014</a>], one with an adult-onset colorectal cancer [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>], and one with adult-onset ovarian cancer [<a class="bk_pop" href="#os-cs.REF.perdu.2010.82">Perdu et al 2010</a>].</div></li></ul></div><div id="os-cs.Affected_Males"><h4>Affected Males</h4><p>There appear to be two distinct phenotypes in males: mild and severe.</p><p><b>Mild <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</b> Mildly affected males have clinical features similar to affected females, including macrocephaly, characteristic facial features, orofacial clefting, hearing loss, and mild-to-moderate learning delays. Mildly affected males are more likely than females to have <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> or musculoskeletal anomalies. Males with the mild phenotype may have a mosaic or constitutional <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each with distinct radiographic features. Shared radiographic findings include cranial sclerosis and sclerosis of the long bones, however metaphyseal striations are more common in mosaic males.</p><ul><li class="half_rhythm"><div><b>Cranial sclerosis and sclerosis of the pelvis and long bones.</b> Best observed on radiographs of the skull, pelvis, femora, and humeri. Sclerosis appears to be more marked compared with females, possibly due to the <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> nature of the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in males.</div></li><li class="half_rhythm"><div><b>Metaphyseal striations</b> have only been observed in one constitutional male [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>], a number of mosaic males [<a class="bk_pop" href="#os-cs.REF.joseph.2010.1506">Joseph et al 2010</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.ch_nier.2012.2946">Chénier et al 2012</a>], and a male with Klinefelter syndrome [<a class="bk_pop" href="#os-cs.REF.fradin.2017.87">Fradin et al 2017</a>]. They are best observed on radiographs of the pelvis, femora, and humeri (see <a href="#os-cs.Pathophysiology">Pathophysiology</a>).</div></li><li class="half_rhythm"><div><b>Characteristic facial features</b> most commonly include frontal bossing, hypertelorism, epicanthal folds, and a depressed nasal bridge.</div></li><li class="half_rhythm"><div><b>Macrocephaly</b> is usually of postnatal onset and is associated with cranial sclerosis. It is usually absolute, (>+3 SD), but can be relative to height or weight.</div></li><li class="half_rhythm"><div><b>Stature.</b> Proportionate short stature of <‒2 SD is commonly associated with OS-CS in males [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Orofacial clefting,</b> typically hard cleft palate, is observed in approximately 66% of mildly affected males [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Hearing loss.</b> Both conductive and sensorineural hearing loss have been reported. Hearing loss is more common in mildly affected males (~85%) compared with females [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Cranial nerve palsies.</b> Rarely, compression of the optic nerve due to bony sclerosis can lead to vision loss, and facial palsies have been reported. This can be progressive, and typically occurs in late adolescence and early adulthood.</div></li><li class="half_rhythm"><div><b>Cognition.</b> Learning issues are more common in surviving males than females, with approximately 80% of males having mild-to-moderate developmental delays [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.ch_nier.2012.2946">Chénier et al 2012</a>, <a class="bk_pop" href="#os-cs.REF.hague.2017.1931">Hague et al 2017</a>].</div></li><li class="half_rhythm"><div><b>Musculoskeletal.</b> Scoliosis (which can be progressive) and joint contractures are commonly observed in mildly affected males [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Congenital anomalies.</b> Congenital heart disease is observed in approximately half of mildly affected males [<a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>]. Brain malformations including ventriculomegaly and partial agenesis of the corpus callosum are also observed in this cohort [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>].</div></li></ul><p><b>Severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</b> The severe phenotype manifests as a multiple-malformation syndrome, and is lethal in mid-to-late gestation or in the neonatal period [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>]. Severely affected males typically have fewer of the characteristic features described in females, in part due to early mortality. In particular, macrocephaly is not always present, and longitudinal metaphyseal striations have not been observed. Severely affected males typically have multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> malformations including limb patterning and skeletal defects (e.g., polysyndactyly, absent or hypoplastic fibulae), congenital heart disease, and brain, genitourinary, and gastrointestinal anomalies.</p><ul><li class="half_rhythm"><div><b>Pregnancy complications.</b> Polyhydramnios has been described in two families, and recurred in multiple pregnancies [<a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>].</div></li><li class="half_rhythm"><div><b>Cranial sclerosis and sclerosis of the pelvis and long bones.</b> Best observed on radiographs of the skull, pelvis, femora, and humeri. This finding is occasionally not observed [<a class="bk_pop" href="#os-cs.REF.jenkins.2009.95">Jenkins et al 2009</a>].</div></li><li class="half_rhythm"><div><b>Macrocephaly</b> is observed in approximately 50% of males with the severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> as either absolute or relative macrocephaly.</div></li><li class="half_rhythm"><div><b>Orofacial clefting.</b> Approximately 50% of males with a severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> have a cleft palate or cleft lip and palate [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>].</div></li><li class="half_rhythm"><div><b>Characteristic facial features.</b> Frontal bossing, hypertelorism, depressed nasal bridge, and micrognathia have been described [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>].</div></li><li class="half_rhythm"><div><b>Musculoskeletal.</b> A striking finding in the majority of severely affected males is the bilateral absence or hypoplasia of the fibulae [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.mi.2020.1439">Mi et al 2020</a>]. Polysyndactyly is also common [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Brain anomalies.</b> Ventriculomegaly is common [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>], as are corpus callosal anomalies.</div></li><li class="half_rhythm"><div><b>Cardiac anomalies.</b> Approximately 40% of severely affected males have <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease. Reported anomalies include hypoplastic left heart, hypoplastic right heart, ventricular septal defects, atrial septal defects, and patent ductus arteriosus [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>].</div></li><li class="half_rhythm"><div><b>Genitourinary anomalies.</b> Nonspecific kidney abnormalities including echogenic kidneys, enlarged kidneys, and abnormal collecting systems are common [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>]. Nephrogenic rests have been identified on postmortem examination in multiple severely affected male fetuses [<a class="bk_pop" href="#os-cs.REF.fukuzawa.2010.791">Fukuzawa et al 2010</a>, <a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>], and may play a role in the development of Wilms tumors [<a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>].</div></li><li class="half_rhythm"><div><b>Gastrointestinal.</b> Omphalocele is the most commonly observed gastrointestinal anomaly, followed by intestinal malrotation [<a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.qu_lin.2015.200">Quélin et al 2015</a>, <a class="bk_pop" href="#os-cs.REF.vasiljevic.2015.302">Vasiljevic et al 2015</a>].</div></li></ul></div><div id="os-cs.Pathophysiology"><h4>Pathophysiology</h4><p>Metaphyseal striations are hypothesized to be due to the presence of two independently acting osteoblast cell lines [<a class="bk_pop" href="#os-cs.REF.rott.2003.281">Rott et al 2003</a>]. This can occur either through differential <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a> in a female or <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a> for an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in a male. This hypothesis would explain why constitutionally affected males with a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>AMER1</i> pathogenic variant and only one osteoblast cell line do not have metaphyseal striations on radiographs.</p></div></div><div id="os-cs.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> for <i>AMER1</i> have been confirmed.</p><p>Initial reports of truncating variants at the 5' end of <i>AMER1</i> predicting a severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> have been disproven [<a class="bk_pop" href="#os-cs.REF.perdu.2010.82">Perdu et al 2010</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>].</p></div><div id="os-cs.Penetrance"><h3>Penetrance</h3><p>Penetrance appears to be 100%, albeit with <a class="def" href="/books/n/gene/glossary/def-item/variable-expressivity/">variable expressivity</a> and severity of the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>, even within families.</p></div><div id="os-cs.Nomenclature"><h3>Nomenclature</h3><p>Previous <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> names for <i>AMER1</i> include <i>WTX</i> and <i>FAM123B.</i></p><p>OS-CS is also known as hyperostosis generalisata with striations.</p><p>In the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bk_pop" href="#os-cs.REF.unger.2023">Unger et al 2023</a>], OS-CS is referred to as <i>AMER1</i>-related osteopathia striata with cranial sclerosis and is included in the osteosclerotic disorders group.</p></div><div id="os-cs.Prevalence"><h3>Prevalence</h3><p>Approximately 90 individuals with molecularly confirmed OS-CS have been reported [Author, personal observation].</p></div></div><div id="os-cs.Genetically_Related_Allelic_Disord"><h2 id="_os-cs_Genetically_Related_Allelic_Disord_">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>AMER1</i>.</p><p><b>Sporadic tumors</b> (including Wilms tumor) occurring as single tumors in the absence of any other findings of osteopathia striata with cranial sclerosis frequently harbor a <a class="def" href="/books/n/gene/glossary/def-item/somatic-pathogenic-variant/">somatic pathogenic variant</a> in <i>AMER1</i> that is <b>not</b> present in the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a>. In these circumstances predisposition to these tumors is not heritable. For more information, see <a href="#os-cs.Cancer_and_Benign_Tumors">Cancer and Benign Tumors</a>.</p></div><div id="os-cs.Differential_Diagnosis"><h2 id="_os-cs_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Females and mildly affected males.</b> Disorders that may present with sclerotic bone disease similar to that observed in females (and mildly affected males) with osteopathia striata with cranial sclerosis (OS-CS) are summarized in <a href="/books/NBK569515/table/os-cs.T.genes_of_interest_in_the_differe/?report=objectonly" target="object" rid-ob="figoboscsTgenesofinterestinthediffere">Table 3</a>. See also the Nosology of Genetic Skeletal Disorders: 2023 Revision, Group 24 – Osteopetrosis and related osteoclast disorders and Group 25 – Osteosclerotic disorders [<a class="bk_pop" href="#os-cs.REF.unger.2023">Unger et al 2023</a>] for a review of additional disorders that may be considered in the differential diagnosis of OS-CS.</p><p><b>Males with a severe <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a></b> present with a multiple-malformation syndrome, usually without metaphyseal striations, making the differential diagnosis very broad. <i>AMER1</i> should be included within the <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> list for any fetal or neonatal multiple-malformation presentation.</p><div id="os-cs.T.genes_of_interest_in_the_differe" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Osteopathia Striata with Cranial Sclerosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.genes_of_interest_in_the_differe/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.genes_of_interest_in_the_differe_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_os-cs.T.genes_of_interest_in_the_differe_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_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4" id="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/OS-CS</th><th headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4" id="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from OS-CS</th></tr></thead><tbody><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ANKH</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cranio-md/">Craniometaphyseal dysplasia, autosomal dominant</a>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis of cranial bones</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Metaphyseal flaring</div></li><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li></ul>
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||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CA2</i>
|
||
<br />
|
||
<a href="/books/n/gene/clcn7/">
|
||
<i>CLCN7</i>
|
||
</a>
|
||
<br />
|
||
<i>LRP5</i>
|
||
<br />
|
||
<i>OSTM1</i>
|
||
<br />
|
||
<i>PLEKHM1</i>
|
||
<br />
|
||
<i>SNX10</i>
|
||
<br />
|
||
<i>TCIRG1</i>
|
||
<br />
|
||
<i>TNFRSF11A</i>
|
||
<br />
|
||
<i>TNFSF11</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Osteopetrosis <sup>1</sup> (OMIM <a href="https://omim.org/phenotypicSeries/PS259700" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS259700</a> & <a href="https://omim.org/phenotypicSeries/PS607634" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS607634</a>)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis of cranial and long bones</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features</div></li><li class="half_rhythm"><div>More diffuse sclerosis of long bones</div></li><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GJA1</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniometaphyseal dysplasia, <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> (OMIM <a href="https://omim.org/entry/218400" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">218400</a>)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis of cranial bones</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Metaphyseal widening</div></li><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>LRP4</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sclerosteosis 2 (OMIM <a href="https://omim.org/entry/614305" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614305</a>)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features</div></li><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PORCN</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/focal-dh/">Focal dermal hypoplasia</a> (Goltz syndrome)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Metaphyseal striations</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ectodermal manifestations</div></li><li class="half_rhythm"><div>Limb malformations</div></li><li class="half_rhythm"><div>Ocular manifestations</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SOST</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endosteal hyperostosis, van Buchem type (van Buchem disease) (See <a href="/books/n/gene/sost/"><i>SOST</i>-Related Sclerosing Bone Dysplasias</a>.)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li><li class="half_rhythm"><div>Progressive skeletal overgrowth</div></li><li class="half_rhythm"><div>Hyperphosphatasemia</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Craniodiaphyseal dysplasia (OMIM <a href="https://omim.org/entry/122860" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">122860</a>)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis; progressive overgrowth of craniofacial bones w/cranial nerve entrapment</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li><li class="half_rhythm"><div>Diaphyses of long bones expanded within the cortices</div></li><li class="half_rhythm"><div>Choanal stenosis a common complication</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sclerosteosis (See <a href="/books/n/gene/sost/"><i>SOST</i>-Related Sclerosing Bone Dysplasias</a>.)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li><li class="half_rhythm"><div>2-3 finger syndactyly, nail dysplasia</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TGFB1</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ced/">Camurati-Engelmann disease</a> (progressive diaphyseal dysplasia)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bony sclerosis of cranial and long bones</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of metaphyseal striations</div></li><li class="half_rhythm"><div>Pronounced diaphyseal hyperostosis of long bones</div></li><li class="half_rhythm"><div>Proximal muscle weakness & wide-based waddling gait</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TONSL</i>
|
||
</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spondyloepimetaphyseal dysplasia, sponastrime type (OMIM <a href="https://omim.org/entry/271510" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271510</a>)</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Metaphyseal striations</td><td headers="hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_os-cs.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Spondylar changes</div></li><li class="half_rhythm"><div>Absence of OS-CS facial characteristics</div></li><li class="half_rhythm"><div>Absence of sclerosis</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>; DiffDx = differential diagnosis; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; 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="os-cs.TF.3.1"><p class="no_margin">See also the Nosology of Genetic Skeletal Disorders: 2023 Revision, Group 24 – Osteopetrosis and related osteoclast disorders and Group 25 – Osteosclerotic disorders [<a class="bk_pop" href="#os-cs.REF.unger.2023">Unger et al 2023</a>].</p></div></dd></dl></div></div></div><p><b>Voorhoeve disease (osteopathia striata)</b> is characterized by <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> metaphyseal striations. Unlike OS-CS, Voorhoeve disease is not associated with cranial sclerosis or macrocephaly. Voorhoeve disease may be inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner or occur in a single family member; the genetic cause(s) of the disorder are unknown.</p></div><div id="os-cs.Management"><h2 id="_os-cs_Management_">Management</h2><p>No consensus clinical diagnostic criteria for osteopathia striata with cranial sclerosis (OS-CS) have been published.</p><div id="os-cs.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with OS-CS, the evaluations summarized in <a href="/books/NBK569515/table/os-cs.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figoboscsTrecommendedevaluationsfollowin">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="os-cs.T.recommended_evaluations_followin" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Osteopathia Striata with Cranial Sclerosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.recommended_evaluations_followin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.recommended_evaluations_followin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_os-cs.T.recommended_evaluations_followin_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_os-cs.T.recommended_evaluations_followin_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skeletal survey – long bones & skull</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for sclerosis &/or metaphyseal striations</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for scoliosis & joint contractures</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ENT assessment</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for orofacial clefting</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing assessment</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate hearing loss</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology assessment</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for optic nerve compression</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constitutional</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth assessment</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for short stature in surviving males (less common in females)</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cognition</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiology assessment incl echocardiography</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for structural heart defects in females & surviving males</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal ultrasound exam</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess for renal anomalies in surviving males</div></li><li class="half_rhythm"><div>To evaluate for nephrogenic rests &/or Wilms tumor in females & males</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_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_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurology assessment incl brain MRI</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for CNS anomalies in surviving males</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastroenterology</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Imaging for malrotation performed as clinically indicated</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & families re nature, MOI, & implications of OS-CS in order to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#os-cs.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td><td headers="hd_h_os-cs.T.recommended_evaluations_followin_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">CNS = central nervous system; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; OS-CS = osteopathia striata with cranial sclerosis</p></div></dd><dt>1. </dt><dd><div id="os-cs.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="os-cs.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management by multidisciplinary specialists, including pediatrician, clinical geneticist, orthopedic surgeon, ENT specialist, and, in the presence of <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> malformations, relevant additional subspecialists, is recommended.</p><div id="os-cs.T.treatment_of_manifestations_in_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Osteopathia Striata with Cranial Sclerosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.treatment_of_manifestations_in_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.treatment_of_manifestations_in_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.treatment_of_manifestations_in_i_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_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_os-cs.T.treatment_of_manifestations_in_i_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_os-cs.T.treatment_of_manifestations_in_i_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_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Management per orthopedic surgeon</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_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_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT may be helpful.</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Orofacial clefting</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Management per ENT surgeon</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Management per audiologist</div></li><li class="half_rhythm"><div>Speech-language therapy</div></li><li class="half_rhythm"><div>Surgical management per otolaryngologist should be considered on a case-by-case basis if underlying pathology involves foraminal compression.</div></li></ul>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Community & support groups for hearing loss</div></li><li class="half_rhythm"><div>Sclerotic bone poses surgical challenges [<a class="bk_pop" href="#os-cs.REF.katsevman.2016.1115">Katsevman et al 2016</a>], and the success of surgical decompression of cranial nerve foramina in OS-CS is not established.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vision loss</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Management per ophthalmologist</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community & support groups for vision loss</td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Surgical management per neurosurgeon should be decided on a case-by-case basis.</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sclerotic bone poses surgical challenges [<a class="bk_pop" href="#os-cs.REF.katsevman.2016.1115">Katsevman et al 2016</a>], and the success of surgical decompression of cranial nerve foramina in OS-CS is not established.</td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cognition</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early intervention services & special education services as indicated</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac anomalies</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per cardiologist</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genitourinary</b>
|
||
<br />
|
||
<b>anomalies</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per urologist &/or nephrologist</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
<br />
|
||
<b>anomalies</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per gastroenterologist &/or surgery</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Wilms tumor &/or</b>
|
||
<br />
|
||
<b>other malignancy</b>
|
||
</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_os-cs.T.treatment_of_manifestations_in_i_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">PT = physical therapy</p></div></dd></dl></div></div></div></div><div id="os-cs.Surveillance"><h3>Surveillance</h3><div id="os-cs.T.recommended_surveillance_for_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Osteopathia Striata with Cranial Sclerosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.T.recommended_surveillance_for_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.T.recommended_surveillance_for_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_os-cs.T.recommended_surveillance_for_ind_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_os-cs.T.recommended_surveillance_for_ind_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_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical assessment for scoliosis & joint contractures</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as indicated</td></tr><tr><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td></tr><tr><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vision</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology eval</td></tr><tr><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cognition</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td></tr><tr><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Wilms tumor</b>
|
||
</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound</td><td headers="hd_h_os-cs.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3 mos until age 7 yrs as per <a href="/books/n/gene/bws/#bws.Management">Beckwith-Wiedemann syndrome</a> guidelines until OS-CS specific guidelines are established <sup>1</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="os-cs.TF.6.1"><p class="no_margin">The association of OS-CS with Wilms tumor has only recently been established [<a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>]. Until there is an evidentiary base for OS-CS-specific surveillance guidelines, surveillance based on Beckwith Wiedemann syndrome guidelines is recommended [<a class="bk_pop" href="#os-cs.REF.brioude.2018.229">Brioude et al 2018</a>; <a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>; Author, personal communication with Professor Stephen Robertson].</p></div></dd></dl></div></div></div></div><div id="os-cs.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from early diagnosis and treatment of hearing and/or vision loss and <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease, from cancer surveillance, and from review for congenital anomalies (males).</p><p>See <a href="#os-cs.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="os-cs.Pregnancy_Management"><h3>Pregnancy Management</h3><p>No specific OS-CS pregnancy management is described, but guidelines for management of pregnant individuals with a skeletal dysplasia should be consulted [<a class="bk_pop" href="#os-cs.REF.savarirayan.2018">Savarirayan et al 2018</a>].</p></div><div id="os-cs.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="os-cs.Genetic_Counseling"><h2 id="_os-cs_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="os-cs.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Osteopathia striata with cranial sclerosis (OS-CS) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner.</p></div><div id="os-cs.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disorder nor will he be <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is an <a class="def" href="/books/n/gene/glossary/def-item/obligate-heterozygote/">obligate heterozygote</a>. Note: If a woman has more than one affected child and no other affected relatives and if the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in her leukocyte DNA, she most likely has <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li><li class="half_rhythm"><div>If a male is the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case):</div><ul><li class="half_rhythm"><div>The mother may be a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a>.</div></li><li class="half_rhythm"><div>The affected male may have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (in which case the mother is not a <a class="def" href="/books/n/gene/glossary/def-item/heterozygote/">heterozygote</a>). About 25% of affected males have the disorder as the result of a <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Note<i>:</i> If a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is found to be mosaic for the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, this is presumed to be due to 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/postzygotic/">postzygotic</a> change in the proband, and is not inherited from either parent.</div></li><li class="half_rhythm"><div>The mother may have <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul></li><li class="half_rhythm"><div>Molecular genetic testing of the mother is recommended to confirm her genetic status and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment.</div></li></ul><p><b>Sibs of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting it in each pregnancy is 50%.</div><ul><li class="half_rhythm"><div class="half_rhythm">Females who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be heterozygotes and will have variable manifestations of OS-CS (see Clinical Description, <a href="#os-cs.Affected_Females">Affected Females</a>)</div></li><li class="half_rhythm"><div class="half_rhythm">Males who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be hemizygotes and will have variable manifestations ranging from mid-late gestation and neonatal lethality to the mild <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> (see Clinical Description, <a href="#os-cs.Affected_Males">Affected Males</a>).</div><div class="half_rhythm">Of the males reported in the literature, approximately half died in mid-late gestation or the neonatal period. However, the incidence of lethality is likely to be under-reported, due to the nonspecific multiple-malformation presentation of males, increasing the likelihood of a missed diagnosis. The low number of reported males suggests that early fetal loss is also possible.</div></li></ul></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family) and if the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population because of the possibility of maternal <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p>
|
||
<b>Parents of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>A female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> may have inherited the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from either her mother or her father, or the pathogenic variant may be <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>. About 45% of affected females have the disorder as the result of a <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Note: Paternal inheritance has only been reported in mosaic fathers [<a class="bk_pop" href="#os-cs.REF.ciceri.2013.1173">Ciceri et al 2013</a>, <a class="bk_pop" href="#os-cs.REF.mi.2020.1439">Mi et al 2020</a>].</div></li><li class="half_rhythm"><div>Detailed evaluation of the parents and review of the extended family history may help distinguish probands with 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> from those with an inherited pathogenic variant. Molecular genetic testing of the mother (and subsequently the father) can help to determine if the pathogenic variant was inherited.</div></li></ul><p><b>Sibs of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs depends on the genetic status of the parents:</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting it in each pregnancy is 50%.</div><ul><li class="half_rhythm"><div class="half_rhythm">Females who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be heterozygotes and will have variable manifestations of OS-CS (see <a href="#os-cs.Clinical_Description">Clinical Description</a>).</div></li><li class="half_rhythm"><div class="half_rhythm">Males who inherit the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will be hemizygotes and will have variable manifestations ranging from mid-late gestation and neonatal lethality to the mild <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> (see <a href="#os-cs.Clinical_Description">Clinical Description</a>).</div><div class="half_rhythm">Of the males reported in the literature, approximately half died in mid-late gestation or the neonatal period. However, the incidence of lethality is likely to be under-reported, due to the nonspecific multiple-malformation presentation of males, increasing the likelihood of a missed diagnosis. The low number of reported males suggests that early fetal loss is also possible.</div></li></ul></li><li class="half_rhythm"><div>If the father of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, it should be presumed he will transmit the <i>AMER1</i> pathogenic variant to all his daughters and none of his sons. Only two instances of paternal vertical transmission have been reported; in both families the fathers were mosaic [<a class="bk_pop" href="#os-cs.REF.ciceri.2013.1173">Ciceri et al 2013</a>, <a class="bk_pop" href="#os-cs.REF.mi.2020.1439">Mi et al 2020</a>].</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family) and if the <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in the leukocyte DNA of either parent, the risk to sibs is 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>.</div></li></ul><p><b>Offspring of a male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Men with an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> will transmit the <i>AMER1</i> pathogenic variant to all of their daughters and none of their sons.</p><p><b>Offspring of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Women with an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> have a 50% chance of transmitting the pathogenic variant to each child:</p><p><b>Other family members.</b> If the mother 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 an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (or, theoretically, the father is <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> for the <i>AMER1</i> pathogenic variant), her (or his) family members may be at risk of being affected.</p><p>Note: Molecular genetic testing may be able to identify the family member in whom a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> arose, information that could help determine genetic risk status of the extended family.</p></div><div id="os-cs.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#os-cs.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk 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, <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a>, or at increased risk of being affected or heterozygous.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#os-cs.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="os-cs.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>AMER1</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="os-cs.Resources"><h2 id="_os-cs_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>Alexander Graham Bell Association for the Deaf and Hard of Hearing</b>
|
||
</div><div><b>Phone:</b> 866-337-5220 (toll-free); 202-337-5221 (TTY)</div><div><b>Fax:</b> 202-337-8314</div><div><b>Email:</b> info@agbell.org</div><div>
|
||
<a href="https://www.agbell.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Listening and Spoken Language Knowledge Center</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>American Society for Deaf Children</b>
|
||
</div><div><b>Phone:</b> 800-942-2732 (ASDC)</div><div><b>Email:</b> info@deafchildren.org</div><div>
|
||
<a href="https://deafchildren.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">deafchildren.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Association of the Deaf</b>
|
||
</div><div><b>Phone:</b> 301-587-1788 (Purple/ZVRS); 301-328-1443 (Sorenson); 301-338-6380 (Convo)</div><div><b>Fax:</b> 301-587-1791</div><div><b>Email:</b> nad.info@nad.org</div><div>
|
||
<a href="https://www.nad.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">nad.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>UCLA International Skeletal Dysplasia Registry (ISDR)</b>
|
||
</div><div><b>Phone:</b> 310-825-8998</div><div>
|
||
<a href="https://www.uclahealth.org/ortho/isdr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Skeletal Dysplasia Registry</a>
|
||
</div></li></ul>
|
||
</div><div id="os-cs.Molecular_Genetics"><h2 id="_os-cs_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="os-cs.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Osteopathia Striata with Cranial Sclerosis: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK569515/table/os-cs.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_os-cs.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_os-cs.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_os-cs.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_os-cs.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_os-cs.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_os-cs.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_os-cs.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/139285" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>AMER1</i>
|
||
</a>
|
||
</td><td headers="hd_b_os-cs.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=139285" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xq11<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_b_os-cs.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q5JTC6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">APC membrane recruitment protein 1</a>
|
||
</td><td headers="hd_b_os-cs.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.LOVD.nl/FAM123B" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FAM123B @ LOVD</a>
|
||
</td><td headers="hd_b_os-cs.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=AMER1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AMER1</a>
|
||
</td><td headers="hd_b_os-cs.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=AMER1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AMER1</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="os-cs.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="os-cs.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Osteopathia Striata with Cranial Sclerosis (<a href="/omim/300373,300647" 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/NBK569515/table/os-cs.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__os-cs.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/300373" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300373</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS; OSCS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/300647" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300647</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">APC MEMBRANE RECRUITMENT PROTEIN 1; AMER1</td></tr></tbody></table></div></div><div id="os-cs.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>AMER1</i> (also known as <i>FAM123B</i> or <i>WTX</i>) encodes adenomatous polyposis coli membrane recruitment protein 1.</p><p>The <i>AMER1</i> protein acts as an inhibitor of the canonic WNT signaling pathway, through the ubiquitination and degradation of beta-catenin [<a class="bk_pop" href="#os-cs.REF.tanneberger.2011.19204">Tanneberger et al 2011</a>]. The WNT signaling pathway acts on a range of cellular processes including body axis patterning and bone morphogenesis. Up- or downregulation of this pathway can have a broad range of phenotypic effects [<a class="bk_pop" href="#os-cs.REF.huybrechts.2020.165">Huybrechts et al 2020</a>].</p><p>Reduced expression of <i>AMER1</i> (e.g., through a <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> variant) leads to an accumulation of beta catenin in the nucleus. This in turn causes upregulation of the WNT pathway and osteoblastic function, leading to bony sclerosis [<a class="bk_pop" href="#os-cs.REF.mi.2020.1439">Mi et al 2020</a>].</p><p>Metaphyseal striations are hypothesized to be due to the presence of two independently acting osteoblast-cell lines [<a class="bk_pop" href="#os-cs.REF.rott.2003.281">Rott et al 2003</a>]. This can occur either through differential <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a> in a female or <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a> for an <i>AMER1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in a male. This hypothesis would explain why constitutionally affected males with a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>AMER1</i> pathogenic variant and only one osteoblast cell line do not have metaphyseal striations on radiographs.</p><p><b>Mechanism of disease causation.</b> Loss of function</p><p><b><i>AMER1</i>-specific laboratory technical considerations.</b>
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<i>AMER1</i> contains two exons, the first of which is noncoding. To date, almost all reported pathogenic variants causing osteopathia striata with cranial sclerosis (OS-CS) are <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> truncating variants in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 2 or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions [Author, personal observation].</p><p>However, two pathogenic variants in the noncoding <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 1 of <i>AMER1</i> have been reported, which may not be captured by traditional sequencing methods [<a class="bk_pop" href="#os-cs.REF.mi.2020.1439">Mi et al 2020</a>].</p><p>Mosaicism has also been reported in several males [<a class="bk_pop" href="#os-cs.REF.joseph.2010.1506">Joseph et al 2010</a>, <a class="bk_pop" href="#os-cs.REF.holman.2011.2397">Holman et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.perdu.2011.383">Perdu et al 2011</a>, <a class="bk_pop" href="#os-cs.REF.ch_nier.2012.2946">Chénier et al 2012</a>, <a class="bk_pop" href="#os-cs.REF.hague.2017.1931">Hague et al 2017</a>], and in a male with Klinefelter syndrome [<a class="bk_pop" href="#os-cs.REF.fradin.2017.87">Fradin et al 2017</a>]. Alternative cell lines, alternative technologies, or an increased depth of sequencing should be considered to identify suspected mosaic pathogenic variants.</p></div><div id="os-cs.Cancer_and_Benign_Tumors"><h3>Cancer and Benign Tumors</h3><p>Somatic <i>AMER1</i> variants are found in 15%-30% of Wilms tumors, evenly divided between mesenchymal- and epithelial-derived tumors [<a class="bk_pop" href="#os-cs.REF.fukuzawa.2009.1063">Fukuzawa et al 2009</a>].</p><p>Early studies suggested that <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>AMER1</i> variants did not predispose to Wilms tumors; however, a recent association has been reported in four individuals including one with bilateral Wilms tumors [<a class="bk_pop" href="#os-cs.REF.bach.2021.396">Bach et al 2021</a>].</p></div></div><div id="os-cs.Chapter_Notes"><h2 id="_os-cs_Chapter_Notes_">Chapter Notes</h2><div id="os-cs.Author_Notes"><h3>Author Notes</h3><p>
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<a href="https://www.mcri.edu.au/users/professor-ravi-savarirayan" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.mcri.edu.au/users/professor-ravi-savarirayan</a>
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</p><p>
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<a href="http://www.skeletaldysplasia.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.skeletaldysplasia.org</a>
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</p></div><div id="os-cs.Acknowledgments"><h3>Acknowledgments</h3><p>Thank you to Professor Stephen Robertson and his working groups for their significant contributions to the OS-CS literature and for communications regarding cancer surveillance recommendations.</p></div><div id="os-cs.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>30 March 2023 (sw) Revision: "<i>AMER1</i>-Related Osteopathia Striata with Cranial Sclerosis" added as synonym; Nosology of Genetic Skeletal Disorders: 2023 Revision [<a class="bk_pop" href="#os-cs.REF.unger.2023">Unger et al 2023</a>] added to <a href="#os-cs.Nomenclature">Nomenclature</a> and <a href="#os-cs.Differential_Diagnosis">Differential Diagnosis</a></div></li><li class="half_rhythm"><div>15 April 2021 (sw) Review posted live</div></li><li class="half_rhythm"><div>4 February 2021 (rs) Original submission</div></li></ul></div></div><div id="os-cs.References"><h2 id="_os-cs_References_">References</h2><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.bach.2021.396">Bach A, Mi J, Hunter M, Halliday BJ, Garcia-Minaur S, Sperotto F, Trevisson E, Markie D, Morison IM, Shinawi M, Willis DN, Robertson SP. Wilms tumor in patients with osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Eur J Hum Genet. </span>2021;<span class="ref-vol">29</span>:396–401.</span> [<a href="/pmc/articles/PMC7940487/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7940487</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32879452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32879452</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.brioude.2018.229">Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macfonal F, Ounap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skorka A, Tatton-Brown K, Tenorio J, Tortora C, Gronskov K, Netchine I, Hennekam RC, Prawitt D, Tumer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER. Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. <span><span class="ref-journal">Nat Rev Endocrinol. </span>2018;<span class="ref-vol">14</span>:229–49.</span> [<a href="/pmc/articles/PMC6022848/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6022848</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29377879" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29377879</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.ch_nier.2012.2946">Chénier S, Noor A, Dupuis L, Stavropoulos DJ, Mendoza-Londono R. Osteopathia striata with cranial sclerosis and developmental delay in a male with a mosaic deletion in chromosome region Xq11.2. <span><span class="ref-journal">Am J Med Genet Part A. </span>2012;<span class="ref-vol">158A</span>:2946–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22987541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22987541</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.ciceri.2013.1173">Ciceri S, Cattaneo E, Fossati C, Radice P, Selicorni A, Perotti D. First evidence of vertical paternal transmission of osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Am J Med Genet Part A. </span>2013;<span class="ref-vol">161A</span>:1173–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23494899" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23494899</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.fradin.2017.87">Fradin M, Collet C, Ract I, Odent S, Guggenbuhl P. First case of osteopathia striata with cranial sclerosis in an adult male with Klinefelter syndrome. <span><span class="ref-journal">Joint Bone Spine. </span>2017;<span class="ref-vol">84</span>:87–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27369646" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27369646</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.fujita.2014.998">Fujita A, Ochi N, Fujikmaki H, Muramatsu H, Takahashi Y, Natsume J, Kojima S, Nakashima M, Tsurusaki Y, Saitsu H, Matsumoto N, Miyake N. A novel <em>WTX</em> mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. <span><span class="ref-journal">Am J Med Genet Part A. </span>2014;<span class="ref-vol">164A</span>:998–1002.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24459086" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24459086</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.fukuzawa.2009.1063">Fukuzawa R, Anaka MR, Weeks RJ, Morison IM, Reeve AE. Canonical WNT signaling determines lineage specificity in Wilms tumour. <span><span class="ref-journal">Oncogene. </span>2009;<span class="ref-vol">28</span>:1063–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19137020" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19137020</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.fukuzawa.2010.791">Fukuzawa R, Holman S, Chow CW, Savarirayan R, Reeve AE, Robertson SP. <em>WTX</em> mutations can occur both early and late in the pathogenesis of Wilms tumour. <span><span class="ref-journal">J Med Genet. </span>2010;<span class="ref-vol">47</span>:791–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20679664" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20679664</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.hague.2017.1931">Hague J, Delon I, Brugger K, Martin H, Sparnon L, Simonic I, Abbs S, Park S-M. <span><span class="ref-journal">Am J Med Genet Part A. </span>2017;<span class="ref-vol">173</span>:1931–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28497491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28497491</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.herman.2013.594">Herman SB, Holman SK, Robertson SP, Davidson L, Taragin B, Samanich J. Severe osteopathia striata with cranial sclerosis in a female case with whole WTX gene deletion. <span><span class="ref-journal">Am J Med Genet A. </span>2013;<span class="ref-vol">161A</span>:594–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23401208" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23401208</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.holman.2011.2397">Holman SK, Daniel P, Jenkins ZA, Herron RL, Morgan T, Savarirayan R, Chow CW, Bohring A, Mosel A, Lacombe D, Steiner B, Schmitt-Mechelke T, Schroter B, Raas-Rothschild A, Garcia-Minaur S, Porteus M, Parker M, Quarrell O, Tapon D, Cormier-Daire V, Manour S, Nash R, Bindoff LA, Fiskerstrand T, Robertson SP. The male phenotype in osteopathia striata congenita with cranial sclerosis. <span><span class="ref-journal">Am J Med Genet Part A. </span>2011;<span class="ref-vol">155A</span>:2397–408.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22043478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22043478</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.holman.2013.251">Holman SK, Morgan T, Baujat G, Cormier-Daire V, Cho T-J, Lees M, Samanich J, Tapon D, Hove HD, Hing A, Hennekam R, Robertson SP. Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the <em>WTX</em> locus. <span><span class="ref-journal">Clin Genet. </span>2013;<span class="ref-vol">83</span>:251–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22670894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22670894</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.huang.2022.389">Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. <span><span class="ref-journal">J Community Genet. </span>2022;<span class="ref-vol">13</span>:389–97.</span> [<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.huybrechts.2020.165">Huybrechts Y, Mortier G, Boudin E, Van Hul W. WNT signaling and bone: lessons from skeletal dysplasias and disorders. <span><span class="ref-journal">Front Endocrinol (Lausanne). </span>2020;<span class="ref-vol">11</span>:165.</span> [<a href="/pmc/articles/PMC7160326/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7160326</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32328030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32328030</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.jenkins.2009.95">Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, Thaller C, Hing AV, Porteous ME, Garcia-Minaur S, Bohring A, Lacombe D, Stewart F, Fiskerstrand T, Bindoff L, Berland S, Ades LC, Tchan M, David A, Wilson LC, Hennekam RCM, Donnai D, Mansour S, Cormier-Daire V, Robertson SP. Germline mutations in <em>WTX</em> cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. <span><span class="ref-journal">Nat Genet. </span>2009;<span class="ref-vol">41</span>:95–100.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19079258" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19079258</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.joseph.2010.1506">Joseph DJ, Ichikawa S, Econs MJ. Mosaicism in osteopathia striata with cranial sclerosis. <span><span class="ref-journal">J Clin Endocrinol Metab. </span>2010;<span class="ref-vol">95</span>:1506–7.</span> [<a href="/pmc/articles/PMC2853980/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2853980</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20150574" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20150574</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.katsevman.2016.1115">Katsevman GA, Turner RC, Lucke-Wolde BP, Sedney CL, Bhatia S. Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma. <span><span class="ref-journal">Acta Neurochir. </span>2016;<span class="ref-vol">158</span>:1115–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27068044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27068044</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.mi.2020.1439">Mi J, Parthasarathy P, Halliday BJ, Morgan T, Dean J, Nowaczyk MJM, Markie D, Robertson SP, Wade EM. Deletion of exon 1 in <em>AMER1</em> in osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Genes. </span>2020;<span class="ref-vol">11</span>:1439.</span> [<a href="/pmc/articles/PMC7760256/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7760256</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33265914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33265914</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.perdu.2010.82">Perdu B, de Freitas F, Frints SGM, Schouten M, Schrander-Stumpel C, Barbosa M, Pinto-Basto J, Reis-Lima M, de Vernejoul MC, Becker K, Freckmann ML, Keymolen K, Haan E, Savarirayan R, Koenic R, Zabel B, Vanhoenacker FM, Van Hul W. Osteopathia striata with cranial sclerosis owing to <em>WTX</em> gene defect. <span><span class="ref-journal">J Bone Miner Res. </span>2010;<span class="ref-vol">25</span>:82–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20209645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20209645</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.perdu.2011.383">Perdu B, Lakeman P, Mortier G, Koenig R, Lachmeijer AMA, Van Hul W. Two novel <em>WTX</em> mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Clin Genet. </span>2011;<span class="ref-vol">80</span>:383–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20950377" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20950377</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.qu_lin.2015.200">Quélin C, Loget P, D'Hervé D, Fradin M, Milon J, Ferry M, Body-Bechou D, Tréguier C, Garcia Hoyos M, Odent S. Osteopathia striata with cranial sclerosis: when a fetal malformation syndrome reveals maternal pathology. <span><span class="ref-journal">Prenatal Diagn. </span>2015;<span class="ref-vol">35</span>:200–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25296999" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25296999</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.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="os-cs.REF.rott.2003.281">Rott HD, Krieg P, Rutschle H, Kraus C. Multiple malformations in a male and maternal osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Genet Couns. </span>2003;<span class="ref-vol">14</span>:281–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14577672" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14577672</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.savarirayan.2018">Savarirayan R, Rossiter JP, Hoover-Fong JE, Irving M, Bompadre V, Goldberg MJ, Bober MB, Cho T-J, Kamps SE, Mackenzie WG, Raggio C, Spencer SS, White KK. Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia. Am J Obs Gyn. 2018;545-62. [<a href="https://pubmed.ncbi.nlm.nih.gov/30048634" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30048634</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.sperotto.2017.674">Sperotto F, Bisogno G, Opocher E, Rossi S, Rigon C, Trevisson E, Mercolini F. Osteopathia striata with cranial sclerosis and Wilms tumor: Coincidence or consequence? <span><span class="ref-journal">Clin Genet. </span>2017;<span class="ref-vol">92</span>:674–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29120061" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29120061</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.tanneberger.2011.19204">Tanneberger K, Pfister AS, Kriz V, Bryja V, Schambony A, Behrens J. Structural and functional characterization of the Wnt inhibitor APC membrane recruitment 1 (Amer1). <span><span class="ref-journal">J Biol Chem. </span>2011;<span class="ref-vol">286</span>:19204–14.</span> [<a href="/pmc/articles/PMC3103299/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3103299</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21498506" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21498506</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.unger.2023">Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. <span><span class="ref-journal">Am J Med Genet A. </span>2023.</span> Epub ahead of print. [<a href="/pmc/articles/PMC10081954/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10081954</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36779427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36779427</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="os-cs.REF.vasiljevic.2015.302">Vasiljevic A, Azzi C, Lacalm A, Combourieu D, Collardeau-Frechon S, Dijoud F, Massardier J, Van Hul W. Fromageoux, Guibaud L, Gaucherand P, Cordier M-P, Massoud M. Prenatal diagnosis of osteopathia striata with cranial sclerosis. <span><span class="ref-journal">Prenatal Diag. </span>2015;<span class="ref-vol">35</span>:302–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25284440" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25284440</span></a>]</div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK569515/?report=reader">PubReader</a></li><li><a href="/books/NBK569515/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK569515" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK569515" style="display:none" title="Cite this Page"><div class="bk_tt">Gear R, Savarirayan R. Osteopathia Striata with Cranial Sclerosis. 2021 Apr 15 [Updated 2023 Mar 30]. 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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301578" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24006547" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div 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1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phelan-McDermid Syndrome-SHANK3 Related.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Phelan K, Rogers RC, Boccuto L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21290788" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NSDHL-Related Disorders.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NSDHL-Related Disorders.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Kurban M, El Feghaly J, Hamie L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=33856753" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=33856753" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d4ec1867c23b31e0e5a668">Osteopathia Striata with Cranial Sclerosis - GeneReviews®</a><div class="ralinkpop offscreen_noflow">Osteopathia Striata with Cranial Sclerosis - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d4ec1784f3725e596c620c">Table B. [OMIM Entries for Osteopathia Striata with Cranial Sclerosis (View All ...</a><div class="ralinkpop offscreen_noflow">Table B. [OMIM Entries for Osteopathia Striata with Cranial Sclerosis (View All in OMIM)]. - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d4ec08cde49f3df70cfc95">RecName: Full=APC membrane recruitment protein 1; Short=Amer1; AltName: Full=Pro...</a><div class="ralinkpop offscreen_noflow">RecName: Full=APC membrane recruitment protein 1; Short=Amer1; AltName: Full=Protein FAM123B; AltName: Full=Wilms tumor gene on the X chromosome protein<div class="brieflinkpopdesc">gi|142984753|sp|Q5JTC6.2|AMER1_HUMA</div></div><div class="tertiary">Protein</div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d4ebf867c23b31e0e520e4">Osteopathia striata with cranial sclerosis</a><div class="ralinkpop offscreen_noflow">Osteopathia striata with cranial sclerosis<div class="brieflinkpopdesc"></div></div><div class="tertiary">MedGen</div></li><li class="ra_qry two_line"><a class="htb" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d4ebf72f30673f7b29c9d5">C0432268[conceptid] <span class="number">(1)</span></a><div class="tertiary">MedGen</div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
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