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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Feingold Syndrome 1" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2019/04/04" /><meta name="citation_author" content="Carlo LM Marcelis" /><meta name="citation_author" content="Arjan PM de Brouwer" /><meta name="citation_pmid" content="20301770" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK7050/" /><meta name="citation_keywords" content="Oculodigitoesophagoduodenal Syndrome" /><meta name="citation_keywords" content="ODED Syndrome" /><meta name="citation_keywords" content="Oculodigitoesophagoduodenal Syndrome" /><meta name="citation_keywords" content="ODED Syndrome" /><meta name="citation_keywords" content="N-myc proto-oncogene protein" /><meta name="citation_keywords" content="MYCN" /><meta name="citation_keywords" content="Feingold Syndrome 1" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Feingold Syndrome 1" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Carlo LM Marcelis" /><meta name="DC.Contributor" content="Arjan PM de Brouwer" /><meta name="DC.Date" content="2019/04/04" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK7050/" /><meta name="description" content="Feingold syndrome 1 (referred to as FS1 in this GeneReview) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild-to-moderate learning disability." /><meta name="og:title" content="Feingold Syndrome 1" /><meta name="og:type" content="book" /><meta name="og:description" content="Feingold syndrome 1 (referred to as FS1 in this GeneReview) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild-to-moderate learning disability." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK7050/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/feingold/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK7050/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK7050_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK7050_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/fahn/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/mccune-albright/" 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="_NBK7050_"><span class="title" itemprop="name">Feingold Syndrome 1</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Oculodigitoesophagoduodenal Syndrome, ODED Syndrome</div><p class="contrib-group"><span itemprop="author">Carlo LM Marcelis</span>, MD and <span itemprop="author">Arjan PM de Brouwer</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK7050_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK7050_ai__"><div class="contrib half_rhythm"><span itemprop="author">Carlo LM Marcelis</span>, MD<div class="affiliation small">Department of Human Genetics<br />Radboud University Nijmegen Medical Center<br />Nijmegen, The Netherlands<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ln.cmuduobdar@silecram.olrac" class="oemail">ln.cmuduobdar@silecram.olrac</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Arjan PM de Brouwer</span>, PhD<div class="affiliation small">Assistant Professor, Department of Human Genetics<br />Radboud University Nijmegen Medical Center<br />Nijmegen, The Netherlands<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ln.cmuduobdar@rewuorbed.najra" class="oemail">ln.cmuduobdar@rewuorbed.najra</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">June 30, 2009</span>; Last Update: <span itemprop="dateModified">April 4, 2019</span>.</p><p><em>Estimated reading time: 17 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="feingold.Summary" itemprop="description"><h2 id="_feingold_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Feingold syndrome 1 (referred to as FS1 in this <i>GeneReview</i>) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild-to-moderate learning disability.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of FS1 is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive clinical findings 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>MYCN</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Gastrointestinal atresia is treated surgically. Mild-to-moderate learning disabilities are treated in the usual manner.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>FS1 is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. Approximately 60% of individuals with Feingold syndrome 1 have an affected parent; the proportion of FS1 caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
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<i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is unknown. Each child of an individual with FS1 has a 50% chance of inheriting the <i>MYCN</i> pathogenic variant. When the <i>MYCN</i> pathogenic variant 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></div></div><div id="feingold.Diagnosis"><h2 id="_feingold_Diagnosis_">Diagnosis</h2><div id="feingold.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Feingold syndrome 1 (FS1) <b>should be suspected</b> in probands with the following clinical findings [<a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al 2008</a>].</p><ul><li class="half_rhythm"><div>Digital anomalies (brachymesophalangy, thumb hypoplasia, toe syndactyly)</div></li><li class="half_rhythm"><div>Microcephaly (occipito-frontal circumference <10th centile)</div></li><li class="half_rhythm"><div>Short palpebral fissures</div></li><li class="half_rhythm"><div>Gastrointestinal atresias, especially esophageal and duodenal, diagnosed pre- or postnatally by imaging studies (usually ultrasound examination, possibly MRI)</div></li></ul></div><div id="feingold.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of FS1 <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive clinical findings and 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>MYCN</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK7050/table/feingold.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobfeingoldTmoleculargenetictestinguse">Table 1</a>). Note: (1) Large contiguous-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions encompassing <i>MYCN</i> and other genes have been reported in individuals with features of FS1 but more complex phenotypes (see <a href="#feingold.Genetically_Related_Allelic_Dis">Genetically Related Disorders</a>). Of note, most individuals with these large deletions are identified by <a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> analysis (CMA) performed in the context of evaluation for multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies. (2) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic 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="#feingold.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (3) Identification of a heterozygous <i>MYCN</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><b>Molecular genetic testing</b> approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> analysis, <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Individuals with the distinctive findings described in <a href="#feingold.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#feingold.Option_1">Option 1</a>), whereas those with atypical findings are more likely to be diagnosed using genomic testing (see <a href="#feingold.Option_2">Option 2</a>).</p><div id="feingold.Option_1"><h4>Option 1</h4><p>When the phenotypic findings suggest the diagnosis of FS1, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>MYCN</i> detects 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-gene deletions/duplications are not detected. Perform <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> first. If no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found, perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect intragenic deletions or duplications.</div><div class="half_rhythm">Note: Gene-targeted methods will detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> up to whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions; however, breakpoints of large deletions and/or <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of adjacent genes may not be determined.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>An intellectual disability</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>MYCN</i> and other genes of interest (see <a href="#feingold.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>. Of note, given the rarity of FS1, some panels for intellectual disability may not include this gene. (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. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK7050/table/feingold.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobfeingoldTmoleculargenetictestinguse">Table 1</a>).</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="feingold.Option_2"><h4>Option 2</h4><p>When the diagnosis of FS1 is not considered because an individual has atypical phenotypic features, <b>comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (which does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>[s] are likely involved) is an option. <b>Exome sequencing</b> is the most commonly used genomic testing method; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible. If <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> is not diagnostic – and particularly when evidence supports <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance – <b><a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a></b> (when clinically available) may be considered to detect (multi)<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="feingold.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Feingold Syndrome 1 (FS1)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.molecular_genetic_testing_use_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_feingold.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_feingold.T.molecular_genetic_testing_use_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_feingold.T.molecular_genetic_testing_use_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MYCN</i>
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</td><td headers="hd_h_feingold.T.molecular_genetic_testing_use_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_feingold.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">59% <sup>4</sup></td></tr><tr><td headers="hd_h_feingold.T.molecular_genetic_testing_use_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_feingold.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9% <sup>6</sup></td></tr><tr><td headers="hd_h_feingold.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Chromosomal microarray (CMA) <sup>7</sup></td><td headers="hd_h_feingold.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 8.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="feingold.TF.1.1"><p class="no_margin">See <a href="/books/NBK7050/#feingold.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="feingold.TF.1.2"><p class="no_margin">See <a href="#feingold.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="feingold.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="feingold.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#feingold.REF.van_bokhoven.2005.465">van Bokhoven et al [2005]</a>, <a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al [2011]</a></p></div></dd><dt>5. </dt><dd><div id="feingold.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. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by <a class="bk_pop" href="#feingold.REF.van_bokhoven.2005.465">van Bokhoven et al [2005]</a>, <a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>, and <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al [2011]</a>) may not be detected by these methods.</p></div></dd><dt>6. </dt><dd><div id="feingold.TF.1.6"><p class="no_margin"><a class="bk_pop" href="#feingold.REF.van_bokhoven.2005.465">van Bokhoven et al [2005]</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al [2011]</a></p></div></dd><dt>7. </dt><dd><div id="feingold.TF.1.7"><p class="no_margin">Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>MYCN</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 2p24.3 region. CMA designs in current clinical use target the 2p24.3 region. Deletions reported in <a class="bk_pop" href="#feingold.REF.van_bokhoven.2005.465">van Bokhoven et al [2005]</a>, <a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>, and <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al [2011]</a> would be detected by CMA.</p></div></dd><dt>8. </dt><dd><div id="feingold.TF.1.8"><p class="no_margin">Larger deletions of <i>MYCN</i> and adjacent genes detected by CMA associated with features of FS1 with additional clinical findings are not included in this table (see <a href="#feingold.Genetically_Related_Allelic_Dis">Genetically Related Disorders</a>).</p></div></dd></dl></div></div></div></div></div></div><div id="feingold.Clinical_Characteristics"><h2 id="_feingold_Clinical_Characteristics_">Clinical Characteristics</h2><div id="feingold.Clinical_Description"><h3>Clinical Description</h3><p>Feingold syndrome 1 (FS1) as described by <a class="bk_pop" href="#feingold.REF.feingold.1975.16">Feingold [1975]</a> and <a class="bk_pop" href="#feingold.REF.brunner.1991.389">Brunner & Winter [1991]</a> is characterized by digital anomalies, microcephaly, facial dysmorphism, gastrointestinal atresias, and learning disability. To date, 69 families with 116 affected individuals having three or more of the core features of FS1 (brachymesophalangy, toe syndactyly, microcephaly, short palpebral fissures, and intestinal atresia) have been reported [<a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al 2008</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al 2008</a>, <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al 2011</a>].</p><p>Features are summarized in <a href="/books/NBK7050/table/feingold.T.features_in_feingold_syndrome/?report=objectonly" target="object" rid-ob="figobfeingoldTfeaturesinfeingoldsyndrome">Table 2</a>.</p><div id="feingold.T.features_in_feingold_syndrome" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Features in Feingold Syndrome 1 (FS1)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.features_in_feingold_syndrome/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.features_in_feingold_syndrome_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">Feature</th><th id="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">% of Persons w/Feature</th></tr></thead><tbody><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Digital anomalies</b>
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</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brachymesophalangy</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Toe syndactyly</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">93%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Thumb hypoplasia</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Microcephaly</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">86%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Facial dysmorphism</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short palpebral fissures</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">73%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Micrognathia</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Atresia</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Esophageal</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">Duodenal</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">Jejunal</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">Anal</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">Multiple</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Mild learning deficit</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Stature <10th centile</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal abnormalities</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cardiac abnormalities</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15%</td></tr><tr><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hearing loss</td><td headers="hd_h_feingold.T.features_in_feingold_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>, <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al [2011]</a></p></div></dd></dl></div></div></div><p>Digital anomalies include brachymesophalangy (shortening of the 2nd and 5th middle phalanx of the hand with clinodactyly of the 5th finger) and thumb hypoplasia (<a class="figpopup" href="/books/NBK7050/figure/feingold.F1/?report=objectonly" target="object" rid-figpopup="figfeingoldF1" rid-ob="figobfeingoldF1">Figures 1</a> and <a class="figpopup" href="/books/NBK7050/figure/feingold.F2/?report=objectonly" target="object" rid-figpopup="figfeingoldF2" rid-ob="figobfeingoldF2">2</a>). Toe syndactyly refers to syndactyly of toes 2-3 and/or 4-5 (<a class="figpopup" href="/books/NBK7050/figure/feingold.F3/?report=objectonly" target="object" rid-figpopup="figfeingoldF3" rid-ob="figobfeingoldF3">Figure 3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figfeingoldF1" co-legend-rid="figlgndfeingoldF1"><a href="/books/NBK7050/figure/feingold.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figfeingoldF1" rid-ob="figobfeingoldF1"><img class="small-thumb" src="/books/NBK7050/bin/feingold-Image001.gif" src-large="/books/NBK7050/bin/feingold-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndfeingoldF1"><h4 id="feingold.F1"><a href="/books/NBK7050/figure/feingold.F1/?report=objectonly" target="object" rid-ob="figobfeingoldF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Typical brachymesophalangy in an adult with FS1 </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figfeingoldF2" co-legend-rid="figlgndfeingoldF2"><a href="/books/NBK7050/figure/feingold.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figfeingoldF2" rid-ob="figobfeingoldF2"><img class="small-thumb" src="/books/NBK7050/bin/feingold-Image002.gif" src-large="/books/NBK7050/bin/feingold-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndfeingoldF2"><h4 id="feingold.F2"><a href="/books/NBK7050/figure/feingold.F2/?report=objectonly" target="object" rid-ob="figobfeingoldF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">X-ray showing typical brachymesophalangy (digits 2 and 5) and thumb hypoplasia </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figfeingoldF3" co-legend-rid="figlgndfeingoldF3"><a href="/books/NBK7050/figure/feingold.F3/?report=objectonly" target="object" title="Figure 3. " class="img_link icnblk_img figpopup" rid-figpopup="figfeingoldF3" rid-ob="figobfeingoldF3"><img class="small-thumb" src="/books/NBK7050/bin/feingold-Image003.gif" src-large="/books/NBK7050/bin/feingold-Image003.jpg" alt="Figure 3. " /></a><div class="icnblk_cntnt" id="figlgndfeingoldF3"><h4 id="feingold.F3"><a href="/books/NBK7050/figure/feingold.F3/?report=objectonly" target="object" rid-ob="figobfeingoldF3">Figure 3. </a></h4><p class="float-caption no_bottom_margin">Typical syndactyly of 2nd and 3rd or 4th and 5th toe </p></div></div><p>Gastrointestinal atresia (esophageal and/or duodenal) is a cause of major medical concern in FS1 and requires immediate surgical intervention (see <a href="#feingold.Management">Management</a>).</p><p>Mild learning deficit is frequent in FS1; most affected individuals are able to live an independent life. Clear intellectual disability is rare, but intelligence is below average when compared to the general population and healthy, unaffected family members.</p><p>Some reports show that growth is impaired in FS1 [<a class="bk_pop" href="#feingold.REF.shawsmith.2005.155">Shaw-Smith et al 2005</a>]. Short stature (height <3rd centile) is uncommon but average height is below that in the general population.</p><p>Associated features that occur in fewer than 50% of affected individuals include the following:</p><ul><li class="half_rhythm"><div><b>Renal abnormalities.</b> Horseshoe kidneys, dysplastic kidneys, hydronephrosis and pelvic dilatation, chronic nephritis, and vesicourethral reflux leading to renal dysplasia and renal failure</div></li><li class="half_rhythm"><div><b>Cardiac abnormalities.</b> Patent ductus arteriosus, multiple ventricular septal defects (VSD), tricuspid valve stenosis and VSD plus tricuspid atresia, and interrupted aortic arch</div></li><li class="half_rhythm"><div><b>Hearing loss.</b> Variable and can include conductive and sensorineural hearing loss; the latter is more commonly reported</div></li></ul></div><div id="feingold.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No significant differences are observed among individuals with deletions or <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>, or frameshift variants.</p></div><div id="feingold.Penetrance"><h3>Penetrance</h3><p>The <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> for major features of FS1, especially digital abnormalities, appears to be 100% but clinical expression can vary considerably.</p></div><div id="feingold.Nomenclature"><h3>Nomenclature</h3><p>Terms used in the past for Feingold syndrome 1:</p><ul><li class="half_rhythm"><div>Microcephaly-oculo-digito-esophageal-duodenal syndrome</div></li><li class="half_rhythm"><div>Microcephaly mesobrachyphalangy tracheoesophageal fistula syndrome</div></li><li class="half_rhythm"><div>Microcephaly-digital anomalies-normal intelligence syndrome</div></li></ul></div><div id="feingold.Prevalence"><h3>Prevalence</h3><p>Prevalence is unknown; FS1 is likely rare. To date, 69 families with 116 affected individuals have been reported [<a class="bk_pop" href="#feingold.REF.blaumeiser.2008.2304">Blaumeiser et al 2008</a>, <a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al 2008</a>, <a class="bk_pop" href="#feingold.REF.cognet.2011.602">Cognet et al 2011</a>].</p></div></div><div id="feingold.Genetically_Related_Allelic_Dis"><h2 id="_feingold_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>The <i>de</i>
|
||
<i>novo</i> <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> pathogenic <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variant p.(Thr58Met) was reported in an individual with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, and neuroblastoma [<a class="bk_pop" href="#feingold.REF.kato.2019.388">Kato et al 2019</a>].</p><p>Contiguous <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions involving <i>MYCN</i> and adjacent genes are relatively common and typically associated with phenotypic findings of FS1 as well as additional findings. To date, nine such individuals have been described [<a class="bk_pop" href="#feingold.REF.celli.2000.436">Celli et al 2000</a>, <a class="bk_pop" href="#feingold.REF.chen.2012.666">Chen et al 2012</a>, <a class="bk_pop" href="#feingold.REF.hempel.2016.152">Hempel et al 2016</a>, <a class="bk_pop" href="#feingold.REF.burnside.2018.1956">Burnside et al 2018</a>].</p></div><div id="feingold.Differential_Diagnosis"><h2 id="_feingold_Differential_Diagnosis_">Differential Diagnosis</h2><div id="feingold.T.other_genes_of_interest_in_th" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Other Genes of Interest in the Differential Diagnosis of Feingold Syndrome 1 (FS1)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.other_genes_of_interest_in_th/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.other_genes_of_interest_in_th_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of Differential Diagnosis Disorder</th></tr><tr><th headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4" id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/FS1</th><th headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4" id="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from FS1</th></tr></thead><tbody><tr><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>CHD7</i>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/charge/">CHARGE syndrome</a>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Esophageal atresia</div></li><li class="half_rhythm"><div>Heart defects</div></li><li class="half_rhythm"><div>Renal abnormalities</div></li></ul>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Coloboma</div></li><li class="half_rhythm"><div>Genital abnormalities</div></li><li class="half_rhythm"><div>Ear anomalies</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MIR17HG</i> <sup>1</sup></td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feingold syndrome 2<br />(OMIM <a href="https://omim.org/entry/614326" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614326</a>)</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Mild growth delay</div></li><li class="half_rhythm"><div>Brachymesophalangy, toe syndactyly, & thumb hypoplasia</div></li><li class="half_rhythm"><div>Learning disabilities</div></li></ul>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence of gastrointestinal abnormalities <sup>2</sup></td></tr><tr><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21 genes <sup>3</sup></td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/fa/">Fanconi anemia</a>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD<br />XL</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Thumb hypoplasia</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Growth restriction</div></li><li class="half_rhythm"><div>Intestinal/anal atresia</div></li><li class="half_rhythm"><div>Renal abnormalities</div></li></ul>
|
||
</td><td headers="hd_h_feingold.T.other_genes_of_interest_in_th_1_1_1_4 hd_h_feingold.T.other_genes_of_interest_in_th_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Absence of brachymesophalangy / toe syndactyly</div></li><li class="half_rhythm"><div>↑ tumor risk (not found in FS1)</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>; 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="feingold.TF.3.1"><p class="no_margin">Feingold syndrome 2 is caused by <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> deletions of <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 13q31.3 including <i>MIR17HG</i> [<a class="bk_pop" href="#feingold.REF.tassano.2013.894">Tassano et al 2013</a>].</p></div></dd><dt>2. </dt><dd><div id="feingold.TF.3.2"><p class="no_margin">To date, seven individuals with Feingold syndrome 2 have been described [<a class="bk_pop" href="#feingold.REF.de_pontual.2011.1026">de Pontual et al 2011</a>, <a class="bk_pop" href="#feingold.REF.ganjavi.2014">Ganjavi et al 2014</a>, <a class="bk_pop" href="#feingold.REF.muriello.2019.410">Muriello et al 2019</a>].</p></div></dd><dt>3. </dt><dd><div id="feingold.TF.3.3"><p class="no_margin"><i>BRCA2</i>, <i>BRIP1</i>, <i>ERCC4</i>, <i>FANCA</i>, <i>FANCB</i>, <i>FANCC</i>, <i>FANCD2</i>, <i>FANCE</i>, <i>FANCF</i>, <i>FANCG</i>, <i>FANCI</i>, <i>FANCL</i>, <i>FANCM</i>, <i>MAD2L2</i>, <i>PALB2</i>, <i>RAD51</i>, <i>RAD51C</i>, <i>RFWD3</i>, <i>SLX4</i>, <i>UBE2T</i>, <i>XRCC2</i></p></div></dd></dl></div></div></div><p><b>VACTERL association</b> (<i>v</i>ertebral defects, <i>a</i>nal atresia, <i>c</i>ardiac defects, <i>t</i>racheoesophageal fistula with <i>e</i>sophageal atresia, <i>r</i>enal and <i>l</i>imb abnormalities) shows considerable overlap with FS1, but the two should be distinguishable by the presence of microcephaly, brachymesophalangy, and toe syndactyly in FS1. The molecular basis of VACTERL association is unknown.</p><p>The brachymesophalangy observed in FS1 is very similar to brachydactyly type A4 (BDA4). The molecular basis of BDA4 is known. Although no pathogenic variants in <i>MYCN</i> have been identified in BDA4, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> of <i>MYCN</i> could be considered in families with BDA4.</p></div><div id="feingold.Management"><h2 id="_feingold_Management_">Management</h2><div id="feingold.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with Feingold syndrome 1 (FS1), the evaluations summarized in <a href="/books/NBK7050/table/feingold.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobfeingoldTrecommendedevaluationsfollo">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="feingold.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Feingold Syndrome 1 (FS1)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evaluation</th><th id="hd_h_feingold.T.recommended_evaluations_follo_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_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hands/Feet</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for digital anomalies.</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hand surgeon</div></li><li class="half_rhythm"><div>Occupational therapy to assess hand function / need for therapy</div></li><li class="half_rhythm"><div>Foot specialist to assess for functional needs</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal tract</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess for gastrointestinal atresia (incl esophageal, duodenal, jejunal, anal).</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterologist / GI surgeon</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl eval of motor, speech-language, general cognitive, & vocational skills</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal abnormalities</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal ultrasound eval</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for renal anomalies.</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac abnormalities</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess for <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart defects.</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pediatric cardiologist</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_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_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval <sup>1</sup></td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Conductive & sensorineural</td></tr><tr><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Miscellaneous</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_feingold.T.recommended_evaluations_follo_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>1. </dt><dd><div id="feingold.TF.4.1"><p class="no_margin">See <a href="/books/n/gene/deafness-overview/">Hereditary Hearing Loss and Deafness Overview</a> for details about audiologic evaluations.</p></div></dd></dl></div></div></div></div><div id="feingold.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Appropriate treatment includes a multidisciplinary approach to address the following possible concerns:</p><ul><li class="half_rhythm"><div>Surgical treatment of gastrointestinal atresia</div></li><li class="half_rhythm"><div>Occupational therapy / surgical intervention for finger/toe anomalies</div></li><li class="half_rhythm"><div>Treatment of cardiac and/or renal anomalies as per standard practice</div></li><li class="half_rhythm"><div>Treatment for significant hearing loss (See <a href="/books/n/gene/deafness-overview/">Hereditary Hearing Loss and Deafness Overview</a>.)</div></li><li class="half_rhythm"><div>Developmental or educational intervention for children with learning difficulties</div></li></ul><div id="feingold.Developmental_Delay__Intellectu"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States (US); standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states and provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center-based; however, for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div><b>IEP services</b> are for those who require specially designed instruction / related services.</div><ul><li class="half_rhythm"><div>IEP services will be reviewed annually to determine if any changes are needed.</div></li><li class="half_rhythm"><div>As required by special education law, children should be in the least restrictive environment at school and included in general education as much as possible and when appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div><b>A 504 plan</b> (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>In the US:</div><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></li></ul></div></div><div id="feingold.Surveillance"><h3>Surveillance</h3><div id="feingold.T.recommended_surveillance_for" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Feingold Syndrome 1</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.recommended_surveillance_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.recommended_surveillance_for_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.recommended_surveillance_for_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_feingold.T.recommended_surveillance_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evaluation</th><th id="hd_h_feingold.T.recommended_surveillance_for_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_feingold.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hands/Feet</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hand function / need for OT</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per OT</td></tr><tr><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>GI tract atresia</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As specified by GI consultants</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Per GI consultants</td></tr><tr><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Education</b>
|
||
</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Routinely, per developmental pediatrician &/or school</td></tr><tr><td headers="hd_h_feingold.T.recommended_surveillance_for_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_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As specified by renal consultants</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Per renal consultants</td></tr><tr><td headers="hd_h_feingold.T.recommended_surveillance_for_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_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As specified by cardiac consultants</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Per cardiologist</td></tr><tr><td headers="hd_h_feingold.T.recommended_surveillance_for_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_feingold.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic reexamination to determine type & extent of hearing loss & success w/hearing habilitation</td><td headers="hd_h_feingold.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating audiologist</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal; OT = occupational therapist/therapy</p></div></dd></dl></div></div></div></div><div id="feingold.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#feingold.Related_Genetic_Counseling_Issu">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="feingold.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 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="feingold.Genetic_Counseling"><h2 id="_feingold_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="feingold.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Feingold syndrome 1 (FS1) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div><div id="feingold.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Many individuals (~60%) diagnosed with FS1 have an affected parent.</div></li><li class="half_rhythm"><div>A <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with FS1 may have the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. <i>De novo</i> pathogenic variants were observed in approximately 40% of individuals with FS1 [<a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al 2008</a>; Author, personal communication].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> found in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, possible explanations include a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> pathogenic variant in the proband or <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a parent. Though theoretically possible, no instances of germline mosaicism have been reported.</div></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with FS1 may appear to be negative because of failure to recognize the disorder in a family member with a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed until appropriate evaluations and/or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have been performed.</div></li><li class="half_rhythm"><div>Note: If the parent is the family member in whom the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> first occurred, the parent may have <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> for the pathogenic variant and may be mildly/minimally affected.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents.</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is affected and/or known to have the <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs is 50%.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a known <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#feingold.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> but are clinically unaffected, the risk to the sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for FS1 because of the theoretic 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 <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with FS1 has a 50% chance of inheriting the <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents: if a parent has the <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the parent's family members may be at risk.</p></div><div id="feingold.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><p><b>Considerations in families with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</b> When neither parent of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> condition has the pathogenic variant identified in the proband or clinical evidence of the disorder, the pathogenic variant is likely <i>de novo</i>. However, non-medical explanations including <a class="def" href="/books/n/gene/glossary/def-item/alternate-paternity/">alternate paternity</a> or maternity (e.g., with assisted reproduction) and undisclosed adoption could also be explored.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul><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="#feingold.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="feingold.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>MYCN</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>Because of the risk for major <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> abnormalities of the gastrointestinal tract, heart, and kidney, high-resolution ultrasound investigations (including fetal echocardiogram) are advised in any pregnancy in which the fetus is known to have an <i>MYCN</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> or in which the genetic status of a fetus at 50% risk is unknown.</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>, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. 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="feingold.Resources"><h2 id="_feingold_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>Children's Craniofacial Association</b>
|
||
</div><div><b>Phone:</b> 800-535-3643</div><div><b>Email:</b> contactCCA@ccakids.com</div><div>
|
||
<a href="https://ccakids.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ccakids.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Face Equality International</b>
|
||
</div><div>United Kingdom</div><div>
|
||
<a href="https://faceequalityinternational.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">faceequalityinternational.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Learning Disabilities Association of America</b>
|
||
</div><div>4156 Library Road</div><div>Pittsburgh PA 15234-1349</div><div><b>Phone:</b> 412-341-1515</div><div><b>Fax:</b> 412-344-0224</div><div>
|
||
<a href="https://ldaamerica.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ldaamerica.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Medline Plus</b>
|
||
</div><div>
|
||
<a href="http://www.nlm.nih.gov/medlineplus/ency/article/000961.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Esophageal atresia</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>REACH</b>
|
||
</div><div>
|
||
<i>Helping children with upper limb differences live life without limits.</i>
|
||
</div><div>United Kingdom</div><div><b>Phone:</b> 03003650078</div><div><b>Email:</b> reach@reach.org.uk</div><div>
|
||
<a href="https://reach.org.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">reach.org.uk</a>
|
||
</div></li></ul>
|
||
</div><div id="feingold.Molecular_Genetics"><h2 id="_feingold_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="feingold.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Feingold Syndrome 1: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_feingold.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_feingold.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_feingold.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_feingold.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_feingold.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_feingold.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/4613" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>MYCN</i>
|
||
</a>
|
||
</td><td headers="hd_b_feingold.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=4613" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2p24<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_b_feingold.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P04198" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">N-myc proto-oncogene protein</a>
|
||
</td><td headers="hd_b_feingold.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=MYCN" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MYCN</a>
|
||
</td><td headers="hd_b_feingold.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MYCN[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MYCN</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="feingold.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="feingold.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Feingold Syndrome 1 (<a href="/omim/164280,164840" 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/NBK7050/table/feingold.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/164280" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">164280</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">FEINGOLD SYNDROME 1; FGLDS1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/164840" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">164840</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MYCN PROTOONCOGENE, bHLH TRANSCRIPTION FACTOR; MYCN</td></tr></tbody></table></div></div><div id="feingold.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The Myc family of proteins is well known for its role in oncogenic processes. Members of this family include c-Myc, N-Myc, and L-Myc. The <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> <i>N-myc</i> was identified by homology with <i>c-Myc</i> in amplified sequences of neuroblastomas.</p><p>c-Myc and N-Myc also play a crucial role in development. Mice deficient for either of these Myc genes die before embryonic day 11.5. Inactivation of murine <i>N-myc</i> demonstrates its developmental importance [<a class="bk_pop" href="#feingold.REF.charron.2002.48">Charron et al 2002</a>, <a class="bk_pop" href="#feingold.REF.knoepfler.2002.2699">Knoepfler et al 2002</a>, <a class="bk_pop" href="#feingold.REF.ota.2007.1583">Ota et al 2007</a>]. <i>N-myc</i> plays a role in branching morphogenesis in the lung and development of the mesonephric tubules, neuroepithelium, sensory ganglia, gut, heart, and limb, many of which are also affected in FS1.</p><p><b>Mechanism of disease causation.</b> Feingold syndrome 1 is caused by a <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> variant resulting in <a class="def" href="/books/n/gene/glossary/def-item/haploinsufficiency/">haploinsufficiency</a> of <i>MYCN.</i></p><p><b><i>MYCN</i>-specific laboratory considerations.</b>
|
||
<i>MYCN</i> encodes three exons. Although <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 1 contains a potential translation start codon, initiation of MYCN protein synthesis commences at the first ATG codon in exon 2 because of an internal ribosome entry site in the 5'-untranslated region [<a class="bk_pop" href="#feingold.REF.jopling.2001.2664">Jopling & Willis 2001</a>]. A <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> nucleotide change in exon 1, which introduced a termination codon, was determined to be benign [<a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al 2008</a>]. The effect of this variant on alternative transcripts and their role in pathogenesis of FS1 is unknown.</p><div id="feingold.T.notable_mycn_variants" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Notable <i>MYCN</i> Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK7050/table/feingold.T.notable_mycn_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__feingold.T.notable_mycn_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_feingold.T.notable_mycn_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_feingold.T.notable_mycn_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001293231.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001293231<wbr style="display:inline-block"></wbr>.1</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001280160.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001280160<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.64C>T</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln22Ter</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Benign variant <sup>1</sup></td></tr><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_005378.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_005378<wbr style="display:inline-block"></wbr>.4</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_005369.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_005369<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.964C>T</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg322Ter</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_4" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Recurrent pathogenic variants <sup>1</sup></td></tr><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1105_1106dupAG</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser369ArgfsTer3</td></tr><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1117C>T</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg373Ter</td></tr><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">c.1178G>A</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">p.Arg393His</td></tr><tr><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">c.1181G>A</td><td headers="hd_h_feingold.T.notable_mycn_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">p.Arg394His</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="feingold.TF.6.1"><p class="no_margin">
|
||
<a class="bk_pop" href="#feingold.REF.marcelis.2008.1125">Marcelis et al [2008]</a>
|
||
</p></div></dd></dl></div></div></div></div><div id="feingold.Cancer_and_Benign_Tumors"><h3>Cancer and Benign Tumors</h3><p>Somatic amplification of <i>MYCN</i> is found in up to 25% of a diverse range of cancers, such as neuroblastoma and skin, lung, and prostate cancer. This invariably leads to overexpression of MYCN resulting in a poor prognosis [<a class="bk_pop" href="#feingold.REF.ruizp_rez.2017.e113">Ruiz-Pérez et al 2017</a>]. This is in sharp contrast to the variants causing FS1, which are <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> variants that without exception result in a loss of function.</p></div></div><div id="feingold.Chapter_Notes"><h2 id="_feingold_Chapter_Notes_">Chapter Notes</h2><div id="feingold.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>4 April 2019 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 September 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 June 2009 (me) Review posted live</div></li><li class="half_rhythm"><div>23 April 2009 (cm) Original submission</div></li></ul></div></div><div id="feingold.References"><h2 id="_feingold_References_">References</h2><div id="feingold.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.blaumeiser.2008.2304">Blaumeiser B, Oehl-Jaschkowitz B, Borozdin W, Kohlhase J. Feingold syndrome associated with two novel MYCN mutations in sporadic and familial cases including monozygotic twins. <span><span class="ref-journal">Am J Med Genet. </span>2008;<span class="ref-vol">146A</span>:2304–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18671284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18671284</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.brunner.1991.389">Brunner HG, Winter RM. Autosomal dominant inheritance of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and oesophageal/duodenal atresia. <span><span class="ref-journal">J Med Genet. </span>1991;<span class="ref-vol">28</span>:389–94.</span> [<a href="/pmc/articles/PMC1016903/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1016903</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1870095" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1870095</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.burnside.2018.1956">Burnside RD, Molinari S, Botti C, Brooks SS, Chung WK, Mehta L, Schwartz S, Papenhausen P. Features of Feingold syndrome 1 dominate in subjects with 2p deletions including MYCN. <span><span class="ref-journal">Am J Med Genet A. </span>2018;<span class="ref-vol">176</span>:1956–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30088856" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30088856</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.celli.2000.436">Celli J, van Beusekom E, Hennekam RC, Gallardo ME, Smeets DF, de Córdoba SR, Innis JW, Frydman M, König R, Kingston H, Tolmie J, Govaerts LC, van Bokhoven H, Brunner HG. Familial syndromic esophageal atresia maps to 2p23-p24. <span><span class="ref-journal">Am J Hum Genet. </span>2000;<span class="ref-vol">66</span>:436–44.</span> [<a href="/pmc/articles/PMC1288096/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1288096</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10677303" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10677303</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.charron.2002.48">Charron J, Gagnon JF, Cadrin-Girard JF. Identification of N-myc regulatory regions involved in embryonic expression. <span><span class="ref-journal">Pediatr Res. </span>2002;<span class="ref-vol">51</span>:48–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11756639" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11756639</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.chen.2012.666">Chen CP, Lin SP, Chern SR, Wu PS, Chang SD, Ng SH, Liu YP, Su JW, Wang W. A de novo 4.4-Mb microdeletion in 2p24.3 → p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome. <span><span class="ref-journal">Eur J Med Genet. </span>2012;<span class="ref-vol">55</span>:666–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22842076" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22842076</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.cognet.2011.602">Cognet M, Nougayrede A, Malan V, Callier P, Cretolle C, Faivre L, Genevieve D, Goldenberg A, Heron D, Mercier S, Philip N, Sigaudy S, Verloes A, Sarnacki S, Munnich A, Vekemans M, Lyonnet S, Etchevers H, Amiel J, de Pontual L. Dissection of the MYCN locus in Feingold syndrome and isolated oesophageal atresia. <span><span class="ref-journal">Eur J Hum Genet. </span>2011;<span class="ref-vol">19</span>:602–6.</span> [<a href="/pmc/articles/PMC3083612/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3083612</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21224895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21224895</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.de_pontual.2011.1026">de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, van Haeringen A, Genevieve D, Goldenberg A, Oufadem M, Manouvrier S, Munnich A, Vidigal JA, Vekemans M, Lyonnet S, Henrion-Caude A, Ventura A, Amiel J. Germline deletion of the miR-17-92 cluster causes growth and skeletal defects in humans. <span><span class="ref-journal">Nat Genet. </span>2011;<span class="ref-vol">43</span>:1026–30.</span> [<a href="/pmc/articles/PMC3184212/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3184212</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21892160" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21892160</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.feingold.1975.16">Feingold M. Case Report 30. <span><span class="ref-journal">Synd Ident. </span>1975;<span class="ref-vol">3</span>:16–7.</span></div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.ganjavi.2014">Ganjavi H, Siu VM, Speevak M, MacDonald PA. A fourth case of Feingold syndrome type 2: psychiatric presentation and management. BMJ Case Rep. 2014;2014. [<a href="/pmc/articles/PMC4244445/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4244445</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25391829" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25391829</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.hempel.2016.152">Hempel A, Pagnamenta AT, Blyth M, Mansour S, McConnell V, Kou I, Ikegawa S, Tsurusaki Y, Matsumoto N, Lo-Castro A, Plessis G, Albrecht B, Battaglia A, Taylor JC, Howard MF, Keays D, Sohal AS, Kühl SJ, Kini U, McNeill A, et al. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome. <span><span class="ref-journal">J Med Genet. </span>2016;<span class="ref-vol">53</span>:152–62.</span> [<a href="/pmc/articles/PMC4789813/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4789813</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26543203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26543203</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.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="feingold.REF.jopling.2001.2664">Jopling CL, Willis AE. N-myc translation is initiated via an internal ribosome entry segment that displays enhanced activity in neuronal cells. <span><span class="ref-journal">Oncogene. </span>2001;<span class="ref-vol">20</span>:2664–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11420678" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11420678</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.kato.2019.388">Kato K, Miya F, Hamada N, Negishi Y, Narumi-Kishimoto Y, Ozawa H, Ito H, Hori I, Hattori A, Okamoto N, Kato M, Tsunoda T, Kanemura Y, Kosaki K, Takahashi Y, Nagata KI, Saitoh S. <em>MYCN</em> de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. <span><span class="ref-journal">J Med Genet. </span>2019;<span class="ref-vol">56</span>:388–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30573562" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30573562</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.knoepfler.2002.2699">Knoepfler PS, Cheng PF, Eisenman RN. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. <span><span class="ref-journal">Genes Dev. </span>2002;<span class="ref-vol">16</span>:2699–712.</span> [<a href="/pmc/articles/PMC187459/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC187459</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12381668" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12381668</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.marcelis.2008.1125">Marcelis CLM, Hol FA, Graham GE, Rieu PNMA, Kellermayer R, Meijer RPP, Lugtenberg D, Scheffer H, van Bokhoven H, Brunner HG, de Brouwer APM. Genotype-phenotype correlations in MYCN-related Feingold syndrome. <span><span class="ref-journal">Hum Mutat. </span>2008;<span class="ref-vol">29</span>:1125–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18470948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18470948</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.muriello.2019.410">Muriello M, Kim AY, Sondergaard Schatz K, Beck N, Gunay-Aygun M, Hoover-Fong JE. Growth hormone deficiency, aortic dilation, and neurocognitive issues in Feingold syndrome 2. <span><span class="ref-journal">Am J Med Genet A. </span>2019;<span class="ref-vol">179</span>:410–6.</span> [<a href="/pmc/articles/PMC7038632/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7038632</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30672094" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30672094</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.ota.2007.1583">Ota S, Zhou ZQ, Keene DR, Knoepfler P, Hurlin PJ. Activities of N-Myc in the developing limb link control of skeletal size with digit separation. <span><span class="ref-journal">Development. </span>2007;<span class="ref-vol">134</span>:1583–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17360777" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17360777</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.rahbari.2016.126">Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, Dominiczak A, Morris A, Porteous D, Smith B, Stratton MR, Hurles ME, et al. Timing, rates and spectra of human germline mutation. <span><span class="ref-journal">Nat Genet. </span>2016;<span class="ref-vol">48</span>:126–33.</span> [<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.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="feingold.REF.ruizp_rez.2017.e113">Ruiz-Pérez MV, Henley AB, Arsenian-Henriksson M. The MYCN protein in health and disease. <span><span class="ref-journal">Genes (Basel). </span>2017;<span class="ref-vol">8</span>:E113. </span> pii. [<a href="/pmc/articles/PMC5406860/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5406860</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28358317" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28358317</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.shawsmith.2005.155">Shaw-Smith C, Willatt L, Thalange N. Growth deficiency in oculodigitoesophagoduodenal (Feingold) syndrome--case report and review of the literature. <span><span class="ref-journal">Clin Dysmorphol. </span>2005;<span class="ref-vol">14</span>:155–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15930908" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15930908</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.tassano.2013.894">Tassano E, Di Rocco M, Signa S, Gimelli G. De novo 13q31.1-q32.1 interstitial deletion encompassing the miR-17-92 cluster in a patient with Feingold syndrome-2. <span><span class="ref-journal">Am J Med Genet A. </span>2013;<span class="ref-vol">161A</span>:894–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23495052" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23495052</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="feingold.REF.van_bokhoven.2005.465">van Bokhoven H, Celli J, van Reeuwijk J, Rinne T, Glaudemans B, van Beusekom E, Rieu P, Newbury-Ecob RA, Chiang C, Brunner HG. MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. <span><span class="ref-journal">Nat Genet. </span>2005;<span class="ref-vol">37</span>:465–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15821734" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15821734</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK7050/?report=reader">PubReader</a></li><li><a href="/books/NBK7050/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK7050" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK7050" style="display:none" title="Cite this Page"><div class="bk_tt">Marcelis CLM, de Brouwer APM. Feingold Syndrome 1. 2009 Jun 30 [Updated 2019 Apr 4]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK7050/pdf/Bookshelf_NBK7050.pdf">PDF version of this page</a> (605K)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#feingold.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#feingold.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#feingold.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#feingold.Genetically_Related_Allelic_Dis" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#feingold.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#feingold.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#feingold.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#feingold.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#feingold.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#feingold.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#feingold.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
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</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=medgen&DbFrom=books&Cmd=Link&LinkName=books_medgen&IdsFromResult=1533348" ref="log$=recordlinks">MedGen</a><div class="brieflinkpop offscreen_noflow">Related information in MedGen</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=1533348" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" 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id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301377" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phelan-McDermid Syndrome-SHANK3 Related.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phelan-McDermid Syndrome-SHANK3 Related.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Phelan K, Rogers RC, Boccuto L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301625" ref="ordinalpos=1&linkpos=2&log$=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> Retinoblastoma.</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> Retinoblastoma.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lohmann DR, Gallie BL. </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" 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