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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Oral-Facial-Digital Syndrome Type I" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/05/11" /><meta name="citation_author" content="Brunella Franco" /><meta name="citation_author" content="Ange-Line Bruel" /><meta name="citation_author" content="Christel Thauvin-Robinet" /><meta name="citation_pmid" content="20301367" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1188/" /><meta name="citation_keywords" content="OFD1" /><meta name="citation_keywords" content="Orofaciodigital Syndrome I" /><meta name="citation_keywords" content="OFD1" /><meta name="citation_keywords" content="Orofaciodigital Syndrome I" /><meta name="citation_keywords" content="Centriole and centriolar satellite protein OFD1" /><meta name="citation_keywords" content="OFD1" /><meta name="citation_keywords" content="Oral-Facial-Digital Syndrome Type I" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Oral-Facial-Digital Syndrome Type I" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Brunella Franco" /><meta name="DC.Contributor" content="Ange-Line Bruel" /><meta name="DC.Contributor" content="Christel Thauvin-Robinet" /><meta name="DC.Date" content="2023/05/11" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1188/" /><meta name="description" content="Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following: oral features (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities); facial features (widely spaced eyes, telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft of the upper lip, micrognathia); digital features (brachydactyly, syndactyly, clinodactyly of the fifth finger, duplicated great toe); polycystic kidney disease; brain MRI findings (intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation); and intellectual disability (in approximately 50% of affected individuals)." /><meta name="og:title" content="Oral-Facial-Digital Syndrome Type I" /><meta name="og:type" content="book" /><meta name="og:description" content="Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following: oral features (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities); facial features (widely spaced eyes, telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft of the upper lip, micrognathia); digital features (brachydactyly, syndactyly, clinodactyly of the fifth finger, duplicated great toe); polycystic kidney disease; brain MRI findings (intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation); and intellectual disability (in approximately 50% of affected individuals)." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1188/" /><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/ofd1/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1188/" /><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="#__NBK1188_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1188_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/opa/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/otc-def/" 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="_NBK1188_"><span class="title" itemprop="name">Oral-Facial-Digital Syndrome Type I</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: OFD1, Orofaciodigital Syndrome I</div><p class="contrib-group"><span itemprop="author">Brunella Franco</span>, MD, <span itemprop="author">Ange-Line Bruel</span>, PhD, and <span itemprop="author">Christel Thauvin-Robinet</span>, MD, PhD.</p><a data-jig="ncbitoggler" href="#__NBK1188_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1188_ai__"><div class="contrib half_rhythm"><span itemprop="author">Brunella Franco</span>, MD<div class="affiliation small">Principal Investigator, Telethon Institute of Genetics and Medicine;<br />Professor, Medical Genetics<br />Department of Translational Medical Sciences<br />University of Naples Federico II<br />Naples, Italy<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ti.megit@ocnarf" class="oemail">ti.megit@ocnarf</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ange-Line Bruel</span>, PhD<div class="affiliation small">Research Engineer, Genetics of Disorders of Development Team<br />University of Burgundy<br />Dijon, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@leurb.enilegna" class="oemail">moc.liamg@leurb.enilegna</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Christel Thauvin-Robinet</span>, MD, PhD<div class="affiliation small">Assistant and Research Investigator, University Hospital Federation - Translational Medicine and Developmental Anomalies;<br />Professor, Medical Genetics<br />Children's Hospital Genetic Center<br />Genetics of Disorders of Development Team<br />University of Burgundy<br />Dijon, France<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="rf.nojid-uhc@nivuaht.letsirhc" class="oemail">rf.nojid-uhc@nivuaht.letsirhc</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">July 24, 2002</span>; Last Update: <span itemprop="dateModified">May 11, 2023</span>.</p><p><em>Estimated reading time: 27 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="ofd1.Summary" itemprop="description"><h2 id="_ofd1_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following: oral features (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities); facial features (widely spaced eyes, telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft of the upper lip, micrognathia); digital features (brachydactyly, syndactyly, clinodactyly of the fifth finger, duplicated great toe); polycystic kidney disease; brain MRI findings (intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation); and intellectual disability (in approximately 50% of affected individuals).</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of OFD1 is established in a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. The diagnosis of OFD1 is established in a male proband with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> pathogenic variant in <i>OFD1</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Surgery for cleft lip/palate, tongue nodules, accessory frenulae, syndactyly, and polydactyly; speech therapy and aggressive treatment of otitis media as needed; removal of accessory teeth; orthodontia for malocclusion; routine treatment for seizures and renal disease; early intervention and individualized education plan as needed; standard treatments for attention-deficit/hyperactivity disorder and/or autistic features; hearing aids and community hearing services as needed.</p><p><i>Surveillance</i>: Annual audiology evaluation and assessment of speech development in children with cleft lip and/or cleft palate; annual dental evaluation or as recommended by the dentist; assessment for new seizures or changes in seizures as recommended by neurologist in those with brain involvement. Annual blood pressure; serum creatinine; and renal, liver, pancreas, and ovarian ultrasound for cystic disease beginning at age ten years. Assess developmental progress, educational needs, and behavioral manifestations at each visit.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to evaluate the genetic status of apparently asymptomatic female relatives (even in the absence of oral, facial, and digital anomalies) to determine if they are at risk for renal disease.</p><p><i>Pregnancy management:</i> Careful monitoring of blood pressure and renal function during pregnancy is warranted.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>OFD1 is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner with, typically, male lethality. The full OFD1 <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> has not been described in males beyond the perinatal period. Approximately 75% of affected females represent <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (i.e., the occurrence of OFD1 in a single family member) and have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>; approximately 25% of females diagnosed with OFD1 have an affected mother (mildly affected females may be diagnosed after the identification of a severely affected individual). If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>OFD1</i> pathogenic variant, the chance of transmitting the pathogenic variant in each pregnancy is 50%; however, most male conceptuses with the <i>OFD1</i> pathogenic variant miscarry. It is possible for an affected male to be born alive, though this is exceedingly rare. Thus, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males. Once the <i>OFD1</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="ofd1.Diagnosis"><h2 id="_ofd1_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for oral-facial-digital syndrome type I (OFD1) have been published.</p><div id="ofd1.Suggestive_Findings"><h3>Suggestive Findings</h3><p>OFD1 <b>should be suspected</b> in females with typical oral, facial, and digital findings, polycystic kidney disease, and/or milia. The oral, facial, and digital findings are also found in other oral-facial-digital syndromes. OFD1 is characterized by renal cystic disease in approximately 50% of individuals and by the <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> inheritance pattern in families with more than one affected individual. Almost all individuals with OFD1 are female; however, a few affected males have been reported. Most affected males are described as malformed fetuses delivered by an affected female.</p><div id="ofd1.Clinical_Features"><h4>Clinical Features</h4><p>
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<b>Oral</b>
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</p><ul><li class="half_rhythm"><div>Tongue anomalies (e.g., lobulated, nodules, ankyloglossia)</div></li><li class="half_rhythm"><div>Cleft palate</div></li><li class="half_rhythm"><div>Alveolar clefts and accessory gingival frenulae</div></li><li class="half_rhythm"><div>Dental anomalies (e.g., missing teeth, extra teeth)</div></li></ul><p>
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<b>Facial</b>
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</p><ul><li class="half_rhythm"><div>Widely spaced eyes, telecanthus, downslanting palpebral fissures</div></li><li class="half_rhythm"><div>Hypoplasia of the alae nasi</div></li><li class="half_rhythm"><div>Median cleft lip, pseudocleft of the upper lip</div></li><li class="half_rhythm"><div>Micrognathia</div></li></ul><p>
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<b>Digital</b>
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</p><ul><li class="half_rhythm"><div>Brachydactyly, syndactyly</div></li><li class="half_rhythm"><div>Clinodactyly of the fifth finger</div></li><li class="half_rhythm"><div>Radial or ulnar deviation of the other fingers, particularly the third</div></li><li class="half_rhythm"><div>Unilateral duplicated hallux (great toe)</div></li></ul><p>
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<b>Other</b>
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</p><ul><li class="half_rhythm"><div>Polycystic kidney disease</div></li><li class="half_rhythm"><div>Intellectual disability</div></li><li class="half_rhythm"><div>Milia</div></li></ul></div><div id="ofd1.Imaging_Features"><h4>Imaging Features</h4><ul><li class="half_rhythm"><div><b>Hand x-rays</b> often demonstrate fine reticular radiolucencies, described as irregular mineralization of the bone, with or without spicule formation of the phalanges.</div></li><li class="half_rhythm"><div><b>Renal ultrasound</b> examination shows renal cysts in at least 50% of individuals.</div></li><li class="half_rhythm"><div><b>Brain MRI</b> most commonly shows intracerebral cysts, agenesis of the corpus callosum, and cerebellar agenesis with or without Dandy-Walker malformation.</div></li></ul></div><div id="ofd1.Family_History"><h4>Family History</h4><p>Family history is consistent with <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> inheritance predominantly affecting females due to male lethality. Absence of a known family history does not preclude the diagnosis.</p></div></div><div id="ofd1.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The diagnosis of OFD1 <b>is established</b> in a female proband with <a href="#ofd1.Suggestive_Findings">suggestive findings</a> 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>OFD1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1188/table/ofd1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobofd1Tmoleculargenetictestingusedin">Table 1</a>).</p><p><b>Male <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The diagnosis of OFD1 <b>is established</b> in a male proband with <a href="#ofd1.Suggestive_Findings">suggestive findings</a> and a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>OFD1</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1188/table/ofd1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobofd1Tmoleculargenetictestingusedin">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic, and both can be used for clinical decision making [<a class="bk_pop" href="#ofd1.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variant" in this section is understood to include any likely pathogenic variant. (2) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> or <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>OFD1</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis.</p><p>Molecular testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) 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="#ofd1.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#ofd1.Option_1">Option 1</a>), whereas those in whom the diagnosis of OFD1 has not been considered are more likely to be diagnosed using genomic testing (see <a href="#ofd1.Option_2">Option 2</a>).</p><div id="ofd1.Option_1"><h4>Option 1</h4><p><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>OFD1</i> is performed first to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</p><p><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>OFD1</i> and other genes of interest (see <a href="#ofd1.Differential_Diagnosis">Differential Diagnosis</a>) is recommended if no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified on single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing. 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 gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="ofd1.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="ofd1.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Oral-Facial-Digital Syndrome Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>OFD1</i>
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</td><td headers="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~80% <sup>4</sup></td></tr><tr><td headers="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_ofd1.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~20% <sup>6</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="ofd1.TF.1.1"><p class="no_margin">See <a href="/books/NBK1188/#ofd1.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="ofd1.TF.1.2"><p class="no_margin">See <a href="#ofd1.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="ofd1.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="ofd1.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#ofd1.REF.nowaczyk.2003.179">Nowaczyk et al [2003]</a>, <a class="bk_pop" href="#ofd1.REF.thauvinrobinet.2006.54">Thauvin-Robinet et al [2006]</a>, <a class="bk_pop" href="#ofd1.REF.prattichizzo.2008.1237">Prattichizzo et al [2008]</a></p></div></dd><dt>5. </dt><dd><div id="ofd1.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>6. </dt><dd><div id="ofd1.TF.1.6"><p class="no_margin">One study found that six of 131 individuals with OFD1 had a <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> ranging in size from one to 14 exons. None had the same deletion. Within this group, 23% of those who did not have a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified on <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> sequencing were found on qPCR to have a single- or multiexon deletion [<a class="bk_pop" href="#ofd1.REF.thauvinrobinet.2009.e320">Thauvin-Robinet et al 2009</a>].</p></div></dd></dl></div></div></div></div></div></div><div id="ofd1.Clinical_Characteristics"><h2 id="_ofd1_Clinical_Characteristics_">Clinical Characteristics</h2><div id="ofd1.Clinical_Description"><h3>Clinical Description</h3><p>The diagnosis of oral-facial-digital syndrome type I (OFD1) is suspected at birth in some infants on the basis of characteristic oral, facial, and digital anomalies; in other instances, the diagnosis is suspected only after polycystic kidney disease is identified in later childhood or adulthood. Almost all affected individuals with OFD1 are female; however, a few affected males have been reported. Most affected males are described as malformed fetuses delivered by a female with OFD1. To date, 234 individuals have been identified with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>OFD1</i> [<a class="bk_pop" href="#ofd1.REF.pezzella.2022.57">Pezzella et al 2022</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="ofd1.T.oralfacialdigital_syndrome_type_i" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Oral-Facial-Digital Syndrome Type I: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.oralfacialdigital_syndrome_type_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.oralfacialdigital_syndrome_type_i_lrgtbl__"><table><thead><tr><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_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_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<b>Oral manifestations</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%-100%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental & tongue abnormalities, aberrant oral frenulae, bifid uvula</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Facial features</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%-80%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysmorphisms, frontal bossing, cleft lip / pseudocleft of upper lip</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Digit anomalies</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%-60%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Syndactyly, clinodactyly, polydactyly, brachydactyly</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Brain malformations</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">65%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hydrocephalus, porencephaly, corpus callosum abnormalities, cortical dysgenesis</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Polycystic kidney disease</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Intellectual disability</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~50%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild to severe</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Milia</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>10%</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div><p><b>Oral manifestations.</b> The tongue is lobulated. Tongue nodules, which are usually hamartomas or lipomas, also occur in at least one third of individuals with OFD1. Ankyloglossia attributable to a short lingual frenulum is common. Cleft hard or soft palate, submucous cleft palate, or highly arched palate occurs in more than 50% of affected individuals. Alveolar clefts and accessory gingival frenulae are common. These fibrous bands are hyperplastic frenulae extending from the buccal mucous membrane to the alveolar ridge, resulting in notching of the alveolar ridges. Dental abnormalities include missing teeth (most common), extra teeth, enamel dysplasia, and malocclusion.</p><p><b>Facial features.</b> Widely spaced eyes (telecanthus) occurs in at least 33% of affected individuals. Hypoplasia of the alae nasi, median cleft lip, or pseudocleft of the upper lip is common. Micrognathia and downslanting palpebral fissures are common.</p><p><b>Digital anomalies.</b> Brachydactyly, syndactyly of varying degrees, and clinodactyly of the fifth finger are common. The other fingers, particularly the third (i.e., middle finger), may show variable radial or ulnar deviation. Duplicated hallux (great toe) occurs in fewer than 50% of affected individuals, and if present is usually unilateral. Preaxial or postaxial polydactyly of the hands occurs in 1%-2% of affected individuals.</p><p><b>Brain malformations.</b> Structural brain abnormalities may occur in as many as 65% of individuals with OFD1 [<a class="bk_pop" href="#ofd1.REF.bisschoff.2013.237">Bisschoff et al 2013</a>, <a class="bk_pop" href="#ofd1.REF.del_giudice.2014.74">Del Giudice et al 2014</a>]. Anomalies most commonly include intracerebral cysts, agenesis of the corpus callosum, and cerebellar agenesis with or without Dandy-Walker malformation. Other reported anomalies include type 2 porencephaly (schizencephalic porencephaly), pachygyria and heterotopias, hydrocephalus, cerebral or cerebellar atrophy, hypothalamic hamartomas, and berry aneurysms, each of which has been described in a few affected individuals.</p><p>Structural brain abnormalities may be accompanied by seizures and ataxia, especially in those with cerebellar atrophy.</p><p><b>Kidney manifestations.</b> Renal cysts can develop from both tubules and glomeruli. The age of onset is most often in adulthood, but renal cysts in children as young as age two years have been described. Although renal cysts have been reported as a prenatal finding [<a class="bk_pop" href="#ofd1.REF.nishimura.1999.506">Nishimura et al 1999</a>], the diagnosis is doubtful in these cases. The risk for significant renal disease appears to be higher than 60% after age 18 years [<a class="bk_pop" href="#ofd1.REF.prattichizzo.2008.1237">Prattichizzo et al 2008</a>, <a class="bk_pop" href="#ofd1.REF.saal.2010.258">Saal et al 2010</a>]. End-stage kidney disease has been reported in affected girls and women ranging in age from 11 to 70 years.</p><p><b>Intellectual disability and neurobehavioral manifestations.</b> It is estimated that as many as 50% of individuals with OFD1 have some degree of intellectual disability or learning disability. Intellectual disability depends in part on the presence of brain abnormalities, but no consistent correlation exists. When present, intellectual disability is usually mild. Severe intellectual disability in the absence of brain malformations appears to be rare [<a class="bk_pop" href="#ofd1.REF.del_giudice.2014.74">Del Giudice et al 2014</a>]. Rarely, behavioral issues (e.g., attention-deficit/hyperactivity disorder, autistic features) are observed.</p><p><b>Milia,</b> small keratinizing cysts, occur in at least 10% of individuals, and are likely more common than reported. Milia most often appears on the scalp, ear pinnae, face, and dorsa of the hands. Milia are usually present in infancy and then resolve, but they can leave pitting scars.</p><p><b>Hair.</b> The hair is often described as dry, coarse, and brittle. Alopecia, usually partial, is an occasional finding. Alopecia following the lines of Blaschko has been described [<a class="bk_pop" href="#ofd1.REF.del_c_boente.1999.367">Del C Boente et al 1999</a>].</p><p><b>Hearing loss</b> from recurrent otitis media, usually associated with cleft palate, has been reported. On occasion, speech can be affected.</p><p><b>Other.</b> Liver, pancreatic, and ovarian cysts may be observed [<a class="bk_pop" href="#ofd1.REF.macca.2009.318">Macca & Franco 2009</a>, <a class="bk_pop" href="#ofd1.REF.chettyjohn.2010.2640">Chetty-John et al 2010</a>].</p><p>Phenotypic variability is often seen in affected females, possibly as a result of random <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a> [<a class="bk_pop" href="#ofd1.REF.morleo.2008.401">Morleo & Franco 2008</a>].</p></div><div id="ofd1.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No convincing <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been reported. The majority of <i>OFD1</i> pathogenic variants are localized within <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 16.</p></div><div id="ofd1.Penetrance"><h3>Penetrance</h3><p>OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected females [<a class="bk_pop" href="#ofd1.REF.mclaughlin.2000.1245">McLaughlin et al 2000</a>].</p></div><div id="ofd1.Nomenclature"><h3>Nomenclature</h3><p>OFD1 was previously called Papillon-Léage-Psaume syndrome.</p></div><div id="ofd1.Prevalence"><h3>Prevalence</h3><p>Prevalence estimates range from 1:50,000 to 1:250,000.</p></div></div><div id="ofd1.Genetically_Related_Allelic_Disorde"><h2 id="_ofd1_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p><i>OFD1</i> pathogenic variants have been reported in males with Joubert syndrome, primary ciliary dyskinesia, and retinitis pigmentosa (see <a href="/books/NBK1188/table/ofd1.T.ofd1_allelic_disorders/?report=objectonly" target="object" rid-ob="figobofd1Tofd1allelicdisorders">Table 3</a>; reviewed in [<a class="bk_pop" href="#ofd1.REF.pezzella.2022.57">Pezzella et al 2022</a>]).</p><div id="ofd1.T.ofd1_allelic_disorders" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p><i>OFD1</i> Allelic Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.ofd1_allelic_disorders/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.ofd1_allelic_disorders_lrgtbl__"><table><thead><tr><th id="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">References</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>OFD1</i>-related <a href="/books/n/gene/joubert/">Joubert syndrome</a></td><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#ofd1.REF.coene.2009.465">Coene et al [2009]</a>, <a class="bk_pop" href="#ofd1.REF.field.2012.806">Field et al [2012]</a>, <a class="bk_pop" href="#ofd1.REF.juricsekhar.2012.695">Juric-Sekhar et al [2012]</a>, <a class="bk_pop" href="#ofd1.REF.thauvinrobinet.2013.86">Thauvin-Robinet et al [2013]</a>, <a class="bk_pop" href="#ofd1.REF.bachmanngagescu.2015.514">Bachmann-Gagescu et al [2015]</a>, <a class="bk_pop" href="#ofd1.REF.srour.2015.744">Srour et al [2015]</a>, <a class="bk_pop" href="#ofd1.REF.suzuki.2016.526">Suzuki et al [2016]</a>, <a class="bk_pop" href="#ofd1.REF.wentzensen.2016.15069">Wentzensen et al [2016]</a>, <a class="bk_pop" href="#ofd1.REF.kane.2017.2">Kane et al [2017]</a>, <a class="bk_pop" href="#ofd1.REF.meng.2017.131">Meng et al [2017]</a>, <a class="bk_pop" href="#ofd1.REF.linpeng.2018.4032543">Linpeng et al [2018]</a>, <a class="bk_pop" href="#ofd1.REF.aljeaid.2019.1010">Aljeaid et al [2019]</a>, <a class="bk_pop" href="#ofd1.REF.zhang.2021.33">Zhang et al [2021]</a>, <a class="bk_pop" href="#ofd1.REF.huang.2022.1038274">Huang et al [2022]</a>, <a class="bk_pop" href="#ofd1.REF.li.2023.1064762">Li et al [2023]</a></td></tr><tr><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>OFD1</i>-related <a href="/books/n/gene/pcd/">primary ciliary dyskinesia</a></td><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#ofd1.REF.bukowybieryllo.2019.769">Bukowy-Bieryllo et al [2019]</a>, <a class="bk_pop" href="#ofd1.REF.hannah.2019.e911">Hannah et al [2019]</a>, <a class="bk_pop" href="#ofd1.REF.hasegawa.2021.241">Hasegawa et al [2021]</a>, <a class="bk_pop" href="#ofd1.REF.yang.2022.697">Yang et al [2022]</a></td></tr><tr><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>OFD1</i>-related <a href="/books/n/gene/rp-overview/">retinitis pigmentosa</a></td><td headers="hd_h_ofd1.T.ofd1_allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#ofd1.REF.webb.2012.3647">Webb et al [2012]</a>, <a class="bk_pop" href="#ofd1.REF.wang.2017.5310924">Wang et al [2017]</a>, <a class="bk_pop" href="#ofd1.REF.chen.2018.145">Chen et al [2018]</a></td></tr></tbody></table></div></div><p><i>OFD1</i> pathogenic variants have also been described in the following reports:</p><ul><li class="half_rhythm"><div>An <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> was reported in male family members with intellectual disability, macrocephaly, obesity, skeletal abnormalities, and a primary ciliary dyskinesia <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> [<a class="bk_pop" href="#ofd1.REF.budny.2006.171">Budny et al 2006</a>]. These findings represent the first indication of a role for <i>OFD1</i> in motile cilia function. Note: The phenotype in this family has been classified as Simpson-Golabi-Behmel type 2 (SGBS2; OMIM <a href="https://omim.org/entry/300209" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300209</a>); however, subsequent studies have demonstrated that the SGBS2 <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> is associated with pathogenic variants in <i>PIGA</i> [<a class="bk_pop" href="#ofd1.REF.fauth.2017.1055">Fauth & Toutain 2017</a>].</div></li><li class="half_rhythm"><div>An <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> was reported in a family in which males had a lethal <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> malformation syndrome characterized by oral, facial, digital, cerebral, and renal anomalies and in utero lethality; disease was caused by a novel <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a> variant in <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 17 of <i>OFD1.</i> Heterozygous females were described to have hyperplastic frenulae and dental anomalies only [<a class="bk_pop" href="#ofd1.REF.tsurusaki.2013.135">Tsurusaki et al 2013</a>].</div></li><li class="half_rhythm"><div>A male fetus with a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>OFD1</i> truncating variant c.2101C>T (p.Gln701Ter) displayed a severe multisystemic condition including severe hypoplasia of the left cardiac ventricle; pregnancy was terminated at 16 1/7 weeks' gestation [<a class="bk_pop" href="#ofd1.REF.bouman.2017.1383">Bouman et al 2017</a>].</div></li></ul></div><div id="ofd1.Differential_Diagnosis"><h2 id="_ofd1_Differential_Diagnosis_">Differential Diagnosis</h2><p>The differential diagnosis of oral-facial-digital syndrome type I (OFD1) includes other oral-facial-digital syndromes and cystic renal diseases.</p><div id="ofd1.T.genes_of_interest_in_the_differen" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Oral-Facial-Digital Syndrome Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.genes_of_interest_in_the_differen/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.genes_of_interest_in_the_differen_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinctive Features / Comment</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>C2CD3</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>C2CD3</i>-related OFD<br />(OMIM <a href="https://omim.org/entry/615948" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615948</a>) /<br /><a href="/books/n/gene/joubert/">JS-OFD</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe microcephaly & ID. Brain MRI shows vermis hypoplasia & MTS.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CEP164</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CEP164-</i>related OFD <sup>1</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postaxial polydactyly, hypotonia, cerebral malformations, hydronephrosis, & urogenital abnormalities. (<i>CEP164</i> is also assoc w/<a href="/books/n/gene/nephron-ov/">nephronophthisis.</a>)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CLUAP1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CLUAP1</i>-related<br />JS-OFD <sup>2</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Epiglottis cleft, short limbs, ID. Brain MRI shows MTS. One individual reported to date.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CPLANE1</i><br />(<i>C5orf42</i>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CPLANE1</i>-related OFD (OMIM <a href="https://omim.org/entry/277170" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">277170</a>) / <a href="/books/n/gene/joubert/">JS-OFD</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polydactyly (particularly central) & cerebellar malformations. Renal agenesis & dysplasia have been described. Brain MRI may show MTS. <sup>3</sup></td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>DDX59</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>DDX59</i>-related OFD (OMIM <a href="https://omim.org/entry/174300" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">174300</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polydactyly & median cleft lip only. Hyperplastic frenula reported in 1 person.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FAM149B1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>FAM149B1</i>-related JS (OMIM <a href="https://omim.org/entry/618763" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618763</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Macrocephaly. Brain MRI shows MTS. Reported in 1 family to date.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>IFT57</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>IFT57</i>-related OFD (OMIM <a href="https://omim.org/entry/617927" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617927</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature, skeletal dysplasia, & brachymesophalangia</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>INTU</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>INTU</i>-related OFD (OMIM <a href="https://omim.org/entry/617926" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617926</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac defects, deafness, polydactyly. (Also assoc w/<i>INTU</i>-related SRPS [OMIM <a href="https://omim.org/entry/617925" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617925</a>].)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIAA0753</i><br />(<i>OFIP</i>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIAA0753</i>-related OFD (OMIM <a href="https://omim.org/entry/617127" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617127</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polydactyly (particularly postaxial). Brain MRI shows vermis hypoplasia & MTS. (Also assoc w<i>/KIAA0753</i>-related short-rib thoracic dysplasia [OMIM <a href="https://omim.org/entry/619479" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619479</a>] & JS [OMIM <a href="https://omim.org/entry/619476" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619476</a>].)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>NEK1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NEK1</i>-related OFD2 (Mohr syndrome) <sup>4</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental agenesis, maxillary hypoplasia, conductive hearing loss, & bilateral tortuosity of retinal veins. (Also assoc w/<i>NEK1</i>-related SRPS [OMIM <a href="https://omim.org/entry/263520" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">263520</a>].)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SCLT1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SCLT1-</i>related OFD <sup>4</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Microcephaly, coloboma, choanal atresia, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease, agenesis of corpus callosum</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SCNM1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SCNM1-</i>related OFD (OMIM <a href="https://omim.org/entry/620107" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">620107</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postaxial polydactyly, tongue nodules, abnormalities of incisors, cleft palate, & retrognathia</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TBC1D32</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TBC1D32-</i>related OFD <sup>4</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Microcephaly, coloboma, choanal atresia, agenesis of corpus callosum, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease, & seizures. 1 person described to date.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TCTN1</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TCTN1-</i>related <a href="/books/n/gene/joubert/">JS</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polydactyly & cerebellar malformations</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TCTN3</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TCTN3</i>-related OFD4<br />(Mohr-Majewski)<br />(OMIM <a href="https://omim.org/entry/258860" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">258860</a>) /<br /><a href="/books/n/gene/joubert/">JS-OFD</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tibial involvement & polydactyly are primary manifestations. Micrognathia. Other findings incl pectus excavatum & short stature.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TMEM107</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TMEM107-</i>related OFD (OMIM <a href="https://omim.org/entry/617563" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617563</a>) / <a href="/books/n/gene/joubert/">JS-OFD</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postaxial polydactyly. ID. Brain MRI shows vermis hypoplasia & MTS.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TMEM138</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TMEM138-</i>related OFD <sup>4</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI shows vermis hypoplasia & MTS. (<i>TMEM138</i> is also assoc w/<a href="/books/n/gene/joubert/">JS</a>.)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TMEM216</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TMEM216-</i>related OFD <sup>4</sup> / <a href="/books/n/gene/joubert/">JS-OFD</a></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polydactyly, nephronophthisis, & cystic kidneys. Brain MRI shows MTS.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TMEM231</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TMEM231-</i>related OFD <sup>4</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI shows vermis hypoplasia & MTS. (<i>TMEM231</i> is also assoc w/<a href="/books/n/gene/joubert/">JS</a>.)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TOPORS</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TOPORS-</i>related OFD <sup>1</sup></td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postaxial polydactyly, hypotonia, cerebral malformations, & urogenital abnormalities. (<i>TOPORS</i> is also assoc w<i>/</i><a href="/books/n/gene/rp-overview/">retinitis pigmentosa.</a>)</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B9D1</i>
|
||
<br />
|
||
<i>B9D2</i>
|
||
<br />
|
||
<i>CC2D2A</i>
|
||
<br />
|
||
<i>CEP290</i>
|
||
<br />
|
||
<i>KIF14</i>
|
||
<br />
|
||
<i>MKS1</i>
|
||
<br />
|
||
<i>NPHP3</i>
|
||
<br />
|
||
<i>RPGRIP1L</i>
|
||
<br />
|
||
<i>TCTN2</i>
|
||
<br />
|
||
<i>TMEM107</i>
|
||
<br />
|
||
<i>TMEM216</i>
|
||
<br />
|
||
<i>TMEM231</i>
|
||
<br />
|
||
<i>TMEM67</i>
|
||
<br />
|
||
<i>TXNDC15</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Meckel syndrome (OMIM <a href="https://omim.org/phenotypicSeries/PS249000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS249000</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CNS malformation (posterior encephalocele, cerebral & cerebellar hypoplasia), polycystic or hypoplastic kidneys, preaxial or postaxial polydactyly, & early demise. Additional findings incl cleft lip & palate, ambiguous genitalia, microcephaly, & microphthalmia. Ocular histopathology reveals retinal dysplasia, coloboma, cataract, & corneal dysgenesis.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ALG5</i>
|
||
<br />
|
||
<i>ALG9</i>
|
||
<br />
|
||
<i>DNAJB11</i>
|
||
<br />
|
||
<i>GANAB</i>
|
||
<br />
|
||
<i>IFT140</i>
|
||
<br />
|
||
<i>PKD1</i>
|
||
<br />
|
||
<i>PKD2</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/pkd-ad/">Autosomal dominant polycystic kidney disease</a> (ADPKD)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ADPKD has been diagnosed in some persons who later were found to have OFD1. <sup>5</sup> In ADPKD, cysts develop from tubules; in OFD1, cysts develop from both tubules & glomeruli (imaging studies cannot always distinguish the renal cystic disease of OFD1 from that of ADPKD & other cystic renal disorders). OFD1 cysts are said to be smaller & more uniform in size than in ADPKD & kidneys are not as enlarged or malformed in OFD1. ADPKD is not assoc w/oral, facial, digital, or brain abnormalities.</td></tr><tr><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PRKACB</i>
|
||
</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardioacrofacial dysplasia 2 (OMIM <a href="https://omim.org/entry/619143" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619143</a>)</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_ofd1.T.genes_of_interest_in_the_differen_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Postaxial polydactyly, brachydactyly, oral frenulae, dental abnormalities, ID, & seizures. Additional findings incl long thorax & heart defects.</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>; CNS = central nervous system; ID = intellectual disability; JS = Joubert syndrome; JS-OFD = Joubert syndrome with oral-facial-digital features; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; MTS = molar tooth sign; OFD = oral-facial-digital; SRPS = short-rib polydactyly syndrome</p></div></dd><dt>1. </dt><dd><div id="ofd1.TF.4.1"><p class="no_margin">
|
||
<a class="bk_pop" href="#ofd1.REF.strong.2021.2409">Strong et al [2021]</a>
|
||
</p></div></dd><dt>2. </dt><dd><div id="ofd1.TF.4.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#ofd1.REF.johnston.2017.a001321">Johnston et al [2017]</a>
|
||
</p></div></dd><dt>3. </dt><dd><div id="ofd1.TF.4.3"><p class="no_margin">
|
||
<a class="bk_pop" href="#ofd1.REF.romani.2015.123">Romani et al [2015]</a>
|
||
</p></div></dd><dt>4. </dt><dd><div id="ofd1.TF.4.4"><p class="no_margin">
|
||
<a class="bk_pop" href="#ofd1.REF.bruel.2017.371">Bruel et al [2017]</a>
|
||
</p></div></dd><dt>5. </dt><dd><div id="ofd1.TF.4.5"><p class="no_margin">
|
||
<a class="bk_pop" href="#ofd1.REF.scolari.1997.1247">Scolari et al [1997]</a>
|
||
</p></div></dd></dl></div></div></div><p>Note: <i>TMEM17</i> may also be of interest in the differential diagnosis of OFD1. A <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> <i>TMEM17</i> variant – expected to be damaging based on variant analyses – was reported in one individual with vermis hypoplasia and the molar tooth sign on brain MRI and postaxial polydactyly [<a class="bk_pop" href="#ofd1.REF.shamseldin.2020.1051">Shamseldin et al 2020</a>].</p><p>OFD types of unknown genetic cause include the following:</p><ul><li class="half_rhythm"><div>OFD3 (OMIM <a href="https://omim.org/entry/258850" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">258850</a>) is characterized by seesaw winking (alternate winking of the eyes) and polydactyly. Myoclonic jerks, profound intellectual disability, bulbous nose, and apparently low-set ears also occur.</div></li><li class="half_rhythm"><div>OFD8 (OMIM <a href="https://omim.org/entry/300484" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300484</a>), apparently inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner, is characterized by the combination of polydactyly, tibial and radial defects, and epiglottal abnormalities, none of which are typical of OFD1.</div></li><li class="half_rhythm"><div>OFD9 (OMIM <a href="https://omim.org/entry/258865" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">258865</a>) includes retinal abnormalities and non-median cleft lip.</div></li><li class="half_rhythm"><div>OFD10 (OMIM <a href="https://omim.org/entry/165590" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">165590</a>) includes short limbs with bilateral radial shortening and fibular agenesis.</div></li><li class="half_rhythm"><div>OFD11 (OMIM <a href="https://omim.org/entry/612913" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">612913</a>) includes odontoid and vertebral abnormalities.</div></li><li class="half_rhythm"><div>OFD12 is described in only one individual with brain malformations, myelomeningocele, short tibiae, and central Y-shaped metacarpal [<a class="bk_pop" href="#ofd1.REF.franco.2016.12">Franco & Thauvin-Robinet 2016</a>].</div></li><li class="half_rhythm"><div>OFD13 is described in only one individual with neuropsychiatric disturbances and leukoaraiosis [<a class="bk_pop" href="#ofd1.REF.franco.2016.12">Franco & Thauvin-Robinet 2016</a>].</div></li></ul></div><div id="ofd1.Management"><h2 id="_ofd1_Management_">Management</h2><p>No clinical practice guidelines for oral-facial-digital syndrome type I (OFD1) have been published.</p><div id="ofd1.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with OFD1, the evaluations summarized in <a href="/books/NBK1188/table/ofd1.T.oralfacialdigital_syndrome_type_i_1/?report=objectonly" target="object" rid-ob="figobofd1Toralfacialdigitalsyndrometypei1">Table 5</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="ofd1.T.oralfacialdigital_syndrome_type_i_1" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Oral-Facial-Digital Syndrome Type I: Recommended Evaluations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.oralfacialdigital_syndrome_type_i_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.oralfacialdigital_syndrome_type_i_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam for oral manifestations that may affect feeding & speech</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental eval</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Digit anomalies</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for digit anomalies.</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Eval of CNS involvement incl brain MRI</div></li><li class="half_rhythm"><div>Neurologic eval w/movement disorder specialist for ataxia</div></li><li class="half_rhythm"><div>EEG in those w/suspected seizures</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Blood pressure</div></li><li class="half_rhythm"><div>Serum creatinine concentration</div></li><li class="half_rhythm"><div>Serum chemistries</div></li><li class="half_rhythm"><div>Urinalysis</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ultrasound exam of kidneys for cysts</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl ultrasound of liver, ovary, & pancreas in those age ≥10 yrs</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Behavior</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Formal, age-appropriate assessment of development & behavior</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_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_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval if cleft palate is present</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of OFD1 to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#ofd1.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul></td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CNS = central nervous system; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; OFD1 = oral-facial-digital syndrome type I</p></div></dd><dt>1. </dt><dd><div id="ofd1.TF.5.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="ofd1.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="ofd1.T.oralfacialdigital_syndrome_type_i_2" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Oral-Facial-Digital Syndrome Type I: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.oralfacialdigital_syndrome_type_i_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.oralfacialdigital_syndrome_type_i_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Oral manifestations</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Reconstructive surgery for clefts of lip &/or palate, tongue nodules, & accessory frenulae</div></li><li class="half_rhythm"><div>Treatment is the same as as that for <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> cleft palate, incl speech therapy & assessment for & aggressive treatment of otitis media.</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental anomalies</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Removal of accessory teeth</div></li><li class="half_rhythm"><div>Orthodontia for malocclusion</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Syndactyly/</b>
|
||
<br />
|
||
<b>Polydactyly</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair as recommended by orthopedist</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal disease</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routine mgmt of renal disease, which may require hemodialysis or peritoneal dialysis & renal transplantation</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development /</b>
|
||
<br />
|
||
<b>Behavioral manifestations</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Early intervention & IEP for those w/developmental issues, learning disabilities, & other cognitive impairments</div></li><li class="half_rhythm"><div>Standard treatments for ADHD &/or autistic features</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing impairment</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing aids may be helpful per otolaryngologist.</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community hearing services through early intervention or school district</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADHD = attention-deficit/hyperactivity disorder; ASM = anti-seizure medication; IEP = individualized education plan</p></div></dd><dt>1. </dt><dd><div id="ofd1.TF.6.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div></div><div id="ofd1.Surveillance"><h3>Surveillance</h3><div id="ofd1.T.oralfacialdigital_syndrome_type_i_3" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Oral-Facial-Digital Syndrome Type I: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.T.oralfacialdigital_syndrome_type_i_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.T.oralfacialdigital_syndrome_type_i_3_lrgtbl__"><table><thead><tr><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of speech development & frequency of ear infections</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually in children if cleft lip &/or cleft palate is present</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental eval</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as recommended by dentist in presence of dental abnormalities</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for new seizures or changes in seizures.</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As recommended by neurologist in those w/brain involvement</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_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_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<ul><li class="half_rhythm"><div>Blood pressure exam</div></li><li class="half_rhythm"><div>Serum creatinine concentration</div></li><li class="half_rhythm"><div>Renal ultrasound for renal cysts</div></li><li class="half_rhythm"><div>Incl ultrasound of liver, pancreas, & ovaries for cystic disease</div></li></ul>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually in individuals age ≥10 yrs</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development/</b>
|
||
<br />
|
||
<b>Behavior</b>
|
||
</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress, educational needs, & for behavioral manifestations.</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_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_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_ofd1.T.oralfacialdigital_syndrome_type_i_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr></tbody></table></div></div></div><div id="ofd1.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to evaluate the genetic status of apparently asymptomatic female relatives (even in the absence of oral, facial, and digital anomalies) to determine if they are at risk for renal disease.</p><p>See <a href="#ofd1.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="ofd1.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Affected pregnant women should undergo careful monitoring of their blood pressure and renal function during pregnancy.</p></div><div id="ofd1.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="ofd1.Genetic_Counseling"><h2 id="_ofd1_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="ofd1.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Oral-facial-digital syndrome type I (OFD1) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner with, typically, male lethality. Almost all affected individuals with OFD1 are female.</p><p>The full OFD1 <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> has not been described in males beyond the perinatal period. Males with a <a class="def" href="/books/n/gene/glossary/def-item/hemizygous/">hemizygous</a> <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> who survive present a phenotype characterized by only some of the clinical features of OFD1, <a href="/books/n/gene/joubert/">Joubert syndrome</a>, <a href="/books/n/gene/rp-overview/">retinitis pigmentosa</a>, or <a href="/books/n/gene/pcd/">primary ciliary dyskinesia</a>, or with a clinical phenotype that is a combination of the different disorders [<a class="bk_pop" href="#ofd1.REF.sakakibara.2019.3">Sakakibara et al 2019</a>, <a class="bk_pop" href="#ofd1.REF.sharma.2016.3181676">Sharma et al 2016</a>, <a class="bk_pop" href="#ofd1.REF.zhang.2020.331">Zhang et al 2020</a>, <a class="bk_pop" href="#ofd1.REF.pezzella.2022.57">Pezzella et al 2022</a>].</p></div><div id="ofd1.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>A female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> may have inherited the <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from her mother or the pathogenic variant may be <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>. (Theoretically, a female proband may have inherited an <i>OFD1</i> pathogenic variant from a father with <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>; however, this has not been reported to date.)</div><ul><li class="half_rhythm"><div>Approximately 75% of affected females represent <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (i.e., the occurrence of OFD1 in a single family member) and have a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> [<a class="bk_pop" href="#ofd1.REF.pezzella.2022.57">Pezzella et al 2022</a>].</div></li><li class="half_rhythm"><div>Approximately 25% of females diagnosed with OFD1 have an affected mother. (Mildly affected females may be diagnosed after the identification of a severely affected individual.)</div></li></ul></li><li class="half_rhythm"><div>Recommendations for the evaluation of the mother 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> include clinical evaluation and <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> for the pathogenic variant in the proband. (Note: Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> and will not detect a pathogenic variant that is present in the germ cells only.)</div></li></ul><p><b>Sibs of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs depends on the genetic status of the parents.</p><ul><li class="half_rhythm"><div>If the mother of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has an <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the chance of transmitting the causative <i>OFD1</i> pathogenic variant in each pregnancy is 50%; however, most male conceptuses with the <i>OFD1</i> pathogenic variant miscarry [<a class="bk_pop" href="#ofd1.REF.macca.2009.318">Macca & Franco 2009</a>]. It is possible for an affected male to be born alive, though this is exceedingly rare. Thus, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case and if the <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> cannot be detected in the leukocyte DNA of the mother, the risk to sibs is slightly greater than that of the general population because of the possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>. Maternal mosaicism for an <i>OFD1</i> pathogenic variant has been reported [<a class="bk_pop" href="#ofd1.REF.wentzensen.2016.15069">Wentzensen et al 2016</a>, <a class="bk_pop" href="#ofd1.REF.gangaram.2022.104496">Gangaram et al 2022</a>]. Paternal germline mosaicism has not been reported to date but remains a possibility.</div></li></ul><p><b>Offspring of a female <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Women with an <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> have a 50% chance of transmitting the pathogenic variant in each pregnancy; however, the expected sex ratio of offspring at delivery is 33% unaffected females, 33% affected females, and 33% unaffected males because of the presumed lethality to affected males during gestation (most male conceptuses with an <i>OFD1</i> pathogenic variant miscarry).</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 mother: if the mother has an <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the mother's family members may be at risk.</p></div><div id="ofd1.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#ofd1.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk of having an <i>OFD1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li></ul></div><div id="ofd1.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the <i>OFD1</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>
|
||
<b>Ultrasound examination</b>
|
||
</p><ul><li class="half_rhythm"><div><b>High-risk pregnancies.</b> In pregnancies of a female with OFD1, which are at 50% risk, prenatal ultrasound examination may detect structural brain malformations (e.g., porencephaly) [<a class="bk_pop" href="#ofd1.REF.carss.2014.3269">Carss et al 2014</a>, <a class="bk_pop" href="#ofd1.REF.alamillo.2015.1073">Alamillo et al 2015</a>] and/or skeletal defects.</div></li><li class="half_rhythm"><div><b>Low-risk pregnancies.</b> In pregnancies not known to be at increased risk for OFD1, the findings of structural brain anomalies <b>and</b> unilateral polydactyly of the great toe (duplicated hallux) should lead to consideration of OFD1. In such instances, it is appropriate to evaluate the mother for manifestations of OFD1.</div></li></ul><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="ofd1.Resources"><h2 id="_ofd1_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>American Cleft Palate-Craniofacial Association</b>
|
||
</div><div><b>Phone:</b> 919-933-9044</div><div>
|
||
<a href="https://acpa-cpf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">acpa-cpf.org</a>
|
||
</div></li><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>Friendly Faces</b>
|
||
</div><div><b>Email:</b> smile@friendlyfaces.org</div><div>
|
||
<a href="https://www.friendlyfaces.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.friendlyfaces.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Kidney Foundation of Canada</b>
|
||
</div><div>Canada</div><div><b>Phone:</b> 514-369-4806</div><div><b>Email:</b> info@kidney.ca</div><div>
|
||
<a href="https://kidney.ca/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">kidney.ca</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Kidney Foundation</b>
|
||
</div><div><b>Phone:</b> 855-NKF-CARES; 855-653-2273</div><div><b>Email:</b> nkfcares@kidney.org</div><div>
|
||
<a href="http://www.kidney.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">kidney.org</a>
|
||
</div></li></ul>
|
||
</div><div id="ofd1.Molecular_Genetics"><h2 id="_ofd1_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="ofd1.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Oral-Facial-Digital Syndrome Type I: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1188/table/ofd1.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_ofd1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_ofd1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_ofd1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_ofd1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_ofd1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_ofd1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_ofd1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/8481" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>OFD1</i>
|
||
</a>
|
||
</td><td headers="hd_b_ofd1.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=8481" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xp22<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_b_ofd1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/O75665" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Centriole and centriolar satellite protein OFD1</a>
|
||
</td><td headers="hd_b_ofd1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.LOVD.nl/OFD1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OFD1 @ LOVD</a>
|
||
</td><td headers="hd_b_ofd1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=OFD1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OFD1</a>
|
||
</td><td headers="hd_b_ofd1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=OFD1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OFD1</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="ofd1.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
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="ofd1.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Oral-Facial-Digital Syndrome Type I (<a href="/omim/300170,311200" 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/NBK1188/table/ofd1.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ofd1.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/300170" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300170</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OFD1 CENTRIOLE AND CENTRIOLAR SATELLITE PROTEIN; OFD1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/311200" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">311200</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OROFACIODIGITAL SYNDROME I; OFD1</td></tr></tbody></table></div></div><div id="ofd1.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Oral-facial-digital syndrome 1 protein (also called centriole and centriolar satellite protein OFD1) occurs in two forms, OFD1-1 (Cxorf5-1) and OFD1-2 (Cxorf5-2), which are differentiated by the use of an alternative <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a>. OFD1-1 is a 1,012-amino acid protein (reference sequence <a href="https://www.ncbi.nlm.nih.gov/protein/NP_003602.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_003602.1</a>); OFD1-2 is a 367-amino acid protein. The two proteins share the first 351 amino acids; OFD1-2 then has a C-terminal region of 16 amino acids. OFD1 was expressed in all adult tissues that were examined by <a class="bk_pop" href="#ofd1.REF.de_conciliis.1998.243">de Conciliis et al [1998]</a>. However, during early development, expression is exclusively in the genital ridges, soon followed by expression in craniofacial structures and the nervous system [<a class="bk_pop" href="#ofd1.REF.ferrante.2001.569">Ferrante et al 2001</a>]. Functional in vivo and in vitro studies have demonstrated that OFD1 is required for ciliogenesis and determination of left-right asymmetry [<a class="bk_pop" href="#ofd1.REF.ferrante.2006.112">Ferrante et al 2006</a>, <a class="bk_pop" href="#ofd1.REF.singla.2010.410">Singla et al 2010</a>]. Recent studies reviewed in <a class="bk_pop" href="#ofd1.REF.morleo.2020.1929">Morleo & Franco [2020]</a> demonstrated that OFD1 has a role in microtubule organization and cell cycle progression [<a class="bk_pop" href="#ofd1.REF.alfieri.2020.101369">Alfieri et al 2020</a>] and protein quality balance [<a class="bk_pop" href="#ofd1.REF.iaconis.2017.1224">Iaconis et al 2017</a>, <a class="bk_pop" href="#ofd1.REF.morleo.2021.e105120">Morleo et al 2021</a>]. A more recent report also indicated that OFD1 acts as a class II nucleation-promoting factor to promote Arp2/3 complex-mediated actin branching [<a class="bk_pop" href="#ofd1.REF.cao.2023.1687">Cao et al 2023</a>].</p><p><b>Mechanism of disease causation.</b> Most <i>OFD1</i> pathogenic variants predict a premature truncation of the protein and apparent loss of function, which is further supported by <i>OFD1</i> intragenic deletions causing the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. However, the <i>OFD1</i> transcript escapes <a class="def" href="/books/n/gene/glossary/def-item/x-chromosome-inactivation/">X-chromosome inactivation</a>; thus, the abnormal protein may theoretically interact with the <a class="def" href="/books/n/gene/glossary/def-item/wild_type/">wild type</a> product to produce a <a class="def" href="/books/n/gene/glossary/def-item/dominant-negative/">dominant-negative</a> effect.</p><p><b><i>OFD1</i>-specific laboratory technical considerations.</b> In females without a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified on <i>OFD1</i> <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/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> should be done, as the deletion could be masked by the <a class="def" href="/books/n/gene/glossary/def-item/wild_type/">wild type</a> <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a>.</p></div></div><div id="ofd1.Chapter_Notes"><h2 id="_ofd1_Chapter_Notes_">Chapter Notes</h2><div id="ofd1.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the Italian Fondazione telethon for continuous support of our research and the patients and their families for participating in research activities. We also thank all the researchers who have contributed to the understanding of this disorder.</p></div><div id="ofd1.Author_History"><h3>Author History</h3><p>Ange-Line Bruel, PhD (2016-present)<br />Brunella Franco, MD (2010-present)<br />Danilo Moretti-Ferreira, PhD; São Paulo State University (2002-2010)<br />Izolda Nunes Guimaraes, PhD; São Paulo State University (2002-2010)<br />Christel Thauvin-Robinet, MD, PhD (2016-present)<br />Helga V Toriello, PhD; Genetics Services Spectrum Health (2002-2023)</p></div><div id="ofd1.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>11 May 2023 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 August 2016 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>28 February 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 October 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>9 March 2007 (ht, cd) Revision: <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-diagnosis/">prenatal diagnosis</a> clinically available</div></li><li class="half_rhythm"><div>14 August 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>29 June 2004 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>24 July 2002 (me) Review posted live</div></li><li class="half_rhythm"><div>27 February 2002 (ht) Original submission</div></li></ul></div></div><div id="ofd1.References"><h2 id="_ofd1_References_">References</h2><div id="ofd1.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.alamillo.2015.1073">Alamillo CL, Powis Z, Farwell K, Shahmirzadi L, Weltmer EC, Turocy J, Lowe T, Kobelka C, Chen E, Basel D, Ashkinadze E, D'Augelli L, Chao E, Tang S. Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. <span><span class="ref-journal">Prenat Diagn. </span>2015;<span class="ref-vol">35</span>:1073–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26147564" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26147564</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.alfieri.2020.101369">Alfieri M, Iaconis D, Tammaro R, Perone L, Calì G, Nitsch L, Dougherty GW, Ragnini-Wilson A, Franco B. The centrosomal/basal body protein OFD1 is required for microtubule organization and cell cycle progression. <span><span class="ref-journal">Tissue Cell. </span>2020;<span class="ref-vol">64</span>:101369. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32473706" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32473706</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.aljeaid.2019.1010">Aljeaid D, Lombardo RC, Witte DP, Hopkin RJ. A novel pathogenic variant in OFD1 results in X-linked Joubert syndrome with orofaciodigital features and pituitary aplasia. <span><span class="ref-journal">Am J Med Genet A. </span>2019;<span class="ref-vol">179</span>:1010–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30895720" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30895720</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.bachmanngagescu.2015.514">Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, Rue TC, Ishak GE, Isabella CR, Gorden N, Adkins J, Boyle EA, de Lacy N, O'Day D, Alswaid A, Ramadevi A R, Lingappa L, Lourenço C, Martorell L, Garcia-Cazorla À, Ozyürek H, Haliloğlu G, Tuysuz B, Topçu M, Chance P, Parisi MA, Glass IA, Shendure J, Doherty D, et al. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. <span><span class="ref-journal">J Med Genet. </span>2015;<span class="ref-vol">52</span>:514–22.</span> [<a href="/pmc/articles/PMC5082428/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5082428</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26092869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26092869</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.bisschoff.2013.237">Bisschoff IJ, Zeschnigk C, Horn D, Wellek B, Rieß A, Wessels M, Willems P, Jensen P, Busche A, Bekkebraten J, Chopra M, Hove HD, Evers C, Heimdal K, Kaiser AS, Kunstmann E, Robinson KL, Linné M, Martin P, McGrath J, Pradel W, Prescott KE, Roesler B, Rudolf G, Siebers-Renelt U, Tyshchenko N, Wieczorek D, Wolff G, Dobyns WB, Morris-Rosendahl DJ. Novel mutations including deletions of the entire OFD1 gene in 30 families with type 1 orofaciodigital syndrome: a study of the extensive clinical variability. <span><span class="ref-journal">Hum Mutat. </span>2013;<span class="ref-vol">34</span>:237–47.</span> [<a href="/pmc/articles/PMC5497464/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5497464</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23033313" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23033313</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.bouman.2017.1383">Bouman A, Alders M, Oostra RJ, van Leeuwen E, Thuijs N, van der Kevie-Kersemaekers A, van Maarle M. Oral-facial-digital syndrome type 1 in males: congenital heart defects are included in its phenotypic spectrum. <span><span class="ref-journal">Am J Med Genet A. </span>2017;<span class="ref-vol">173</span>:1383–89.</span> [<a href="/pmc/articles/PMC5413846/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5413846</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28371265" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28371265</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.bruel.2017.371">Bruel AL, Franco B, Duffourd Y, Thevenon J, Jego L, Lopez E, Deleuze JF, Doummar D, Giles RH, Johnson CA, Huynen MA, Chevrier V, Burglen L, Morleo M, Desguerres I, Pierquin G, Doray B, Gilbert-Dussardier B, Reversade B, Steichen-Gersdorf E, Baumann C, Panigrahi I, Fargeot-Espaliat A, Dieux A, David A, Goldenberg A, Bongers E, Gaillard D, Argente J, Aral B, Gigot N, St-Onge J, Birnbaum D, Phadke SR, Cormier-Daire V, Eguether T, Pazour GJ, Herranz-Pérez V, Goldstein JS, Pasquier L, Loget P, Saunier S, Mégarbané A, Rosnet O, Leroux MR, Wallingford JB, Blacque OE, Nachury MV, Attie-Bitach T, Rivière JB, Faivre L, Thauvin-Robinet C. Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes. <span><span class="ref-journal">J Med Genet. </span>2017;<span class="ref-vol">54</span>:371–80.</span> [<a href="/pmc/articles/PMC5557276/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5557276</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28289185" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28289185</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.budny.2006.171">Budny B, Chen W, Omran H, Friegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. <span><span class="ref-journal">Hum Genet. </span>2006;<span class="ref-vol">120</span>:171–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16783569" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16783569</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.bukowybieryllo.2019.769">Bukowy-Bieryllo Z, Rabiasz A, Dabrowski M, Pogorzelski A, Wojda A, Dmenska H, Grzela K, Sroczynski J, Witt M, Zietkiewicz E. Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms. <span><span class="ref-journal">J Med Genet. </span>2019;<span class="ref-vol">56</span>:769–77.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31366608" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31366608</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.cao.2023.1687">Cao M, Zou X, Li C, Lin Z, Wang N, Zou Z, Ye Y, Seemann J, Levine B, Tang Z, Zhong Q. 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Comment on "Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome.". <span><span class="ref-journal">Prenat Diagn. </span>2017;<span class="ref-vol">37</span>:1055–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29057530" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29057530</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.ferrante.2001.569">Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B. 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Care4Rare Canada Consortium; Boycott K, Brais B, Boucher RM, Rouleau GA, Katsanis N, Majewski J, Elpeleg O, Kukolich MK, Shalev S, Michaud JL. Joubert syndrome in French Canadians and identification of mutations in CEP104. <span><span class="ref-journal">Am J Hum Genet. </span>2015;<span class="ref-vol">97</span>:744–53.</span> [<a href="/pmc/articles/PMC4667103/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4667103</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26477546" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26477546</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.strong.2021.2409">Strong A, Simone L, Krentz A, Vaccaro C, Watson D, Ron H, Kalish JM, Pedro HF, Zackai EH, Hakonarson H. Expanding the genetic landscape of oral-facial-digital syndrome with two novel genes. <span><span class="ref-journal">Am J Med Genet A. </span>2021;<span class="ref-vol">185</span>:2409–16.</span> [<a href="/pmc/articles/PMC8361718/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8361718</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34132027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34132027</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.suzuki.2016.526">Suzuki T, Miyake N, Tsurusaki Y, Okamoto N, Alkindy A, Inaba A, Sato M, Ito S, Muramatsu K, Kimura S, Ieda D, Saitoh S, Hiyane M, Suzumura H, Yagyu K, Shiraishi H, Nakajima M, Fueki N, Habata Y, Ueda Y, Komatsu Y, Yan K, Shimoda K, Shitara Y, Mizuno S, Ichinomiya K, Sameshima K, Tsuyusaki Y, Kurosawa K, Sakai Y, Haginoya K, Kobayashi Y, Yoshizawa C, Hisano M, Nakashina M, Saitsu H, Takeda S, Matsumoto N. Molecular genetic analysis of 30 families with Joubert syndrome. <span><span class="ref-journal">Clin Genet. </span>2016;<span class="ref-vol">90</span>:526–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27434533" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27434533</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.thauvinrobinet.2006.54">Thauvin-Robinet C, Cossee M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y, Bieth E, Layet V, Parent P, David A, Goldenberg A, Mortier G, Heron D, Sagot P, Bouvier AM, Huet F, Cusin V, Donzel A, Devys D, Teyssier JR, Faivre L. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. <span><span class="ref-journal">J Med Genet. </span>2006;<span class="ref-vol">43</span>:54–61.</span> [<a href="/pmc/articles/PMC2564504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2564504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16397067" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16397067</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.thauvinrobinet.2009.e320">Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Lasurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frebourg T, Faivre L. Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. <span><span class="ref-journal">Hum Mutat. </span>2009;<span class="ref-vol">30</span>:E320–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19023858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19023858</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.thauvinrobinet.2013.86">Thauvin-Robinet C, Thomas S, Sinico M, Aral B, Burglen L, Gigot N, Dollfus H, Rossignol S, Raynaud M, Philippe C, Badens C, Touraine R, Gomes C, Franco B, Lopez E, Elkhartoufi N, Faivre L, Munnich A, Boddaert N, Van Maldergerm L, Encha-Razavi F, Lyonnet S, Vekemans M, Escudier E, Attié-Bitach T. OFD1 mutations in males: phenotypic spectrum and ciliary basal body docking impairment. <span><span class="ref-journal">Clin Genet. </span>2013;<span class="ref-vol">84</span>:86–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23036093" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23036093</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.tsurusaki.2013.135">Tsurusaki Y, Kosho T, Hatasaki K, Narumi Y, Wakui K, Fukushima Y, Doi H, Saitsu H, Miyake N, Matsumoto N. Exome sequencing in a family with an X-linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients. <span><span class="ref-journal">Clin Genet. </span>2013;<span class="ref-vol">83</span>:135–44.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22548404" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22548404</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.wang.2017.5310924">Wang X, Zheng C, Liu W, Yang H. Retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis in a 6-year-old boy with OFD1 gene mutation. <span><span class="ref-journal">Case Rep Ophthalmol Med. </span>2017;<span class="ref-vol">2017</span>:5310924. </span> [<a href="/pmc/articles/PMC5278184/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5278184</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28191358" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28191358</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.webb.2012.3647">Webb TR, Parfitt DA, Gardner JC, Martinez A, Bevilacqua D, Davidson AE, Zito I, Thiselton DL, Ressa JH, Apergi M, Schwarz N, Kanuga N, Michaelides M, Cheetham ME, Gorin MB, Hardcastle AJ. Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23). <span><span class="ref-journal">Hum Mol Genet. </span>2012;<span class="ref-vol">21</span>:3647–54.</span> [<a href="/pmc/articles/PMC3406759/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3406759</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22619378" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22619378</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.wentzensen.2016.15069">Wentzensen IM, Johnston JJ, Patton JH, Graham JM, Sapp JC, Biesecker LG. Exome sequencing identifies a mutation in OFD1 in a male with Joubert syndrome, orofaciodigital spectrum anomalies and complex polydactyly. <span><span class="ref-journal">Hum Genome Var. </span>2016;<span class="ref-vol">3</span>:15069.</span> [<a href="/pmc/articles/PMC4760119/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4760119</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27081566" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27081566</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.yang.2022.697">Yang B, Lei C, Yang D, Lu C, Xu Y, Wang L, Guo T, Wang R, Luo H. Identification of a novel variant in a patient with primary ciliary dyskinesia. <span><span class="ref-journal">Pharmgenomics Pers Med. </span>2022;<span class="ref-vol">15</span>:697–704.</span> [<a href="/pmc/articles/PMC9285985/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9285985</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35847568" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35847568</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.zhang.2020.331">Zhang H-W, Su B-G, Yao Y. OFD1 mutation induced renal failure and polycystic kidney disease in a pair of childhood male twins in China. <span><span class="ref-journal">World J Clin Cases. </span>2020;<span class="ref-vol">8</span>:331–6.</span> [<a href="/pmc/articles/PMC7000948/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7000948</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32047782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32047782</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ofd1.REF.zhang.2021.33">Zhang YW, Qu H, Long N, Leng X, Liu Y, Yang Y. A rare mutant of OFD1 gene responsible for Joubert syndrome with significant phenotype variation. <span><span class="ref-journal">Mol Genet Genomics. </span>2021;<span class="ref-vol">296</span>:33–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32944789" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32944789</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301712" 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> PORCN-Related Developmental Disorders.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> PORCN-Related Developmental Disorders.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Sutton VR. </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/20301668" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia B.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24006547" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Ornithine Transcarbamylase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lichter-Konecki U, Caldovic L, Morizono H, Simpson K, Ah Mew N, MacLeod E. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301578" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Hemophilia A.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Konkle BA, Nakaya Fletcher S. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301469" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span 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