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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>MID1-Related Opitz G/BBB Syndrome - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="MID1-Related Opitz G/BBB Syndrome">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2023/10/19">
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<meta name="citation_author" content="Germana Meroni">
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<meta name="citation_keywords" content="X-Linked Opitz Syndrome (XLOS)">
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<meta name="citation_keywords" content="X-Linked Opitz G/BBB Syndrome">
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<meta name="citation_keywords" content="X-Linked Opitz Syndrome (XLOS)">
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<meta name="citation_keywords" content="X-Linked Opitz G/BBB Syndrome">
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<meta name="citation_keywords" content="E3 ubiquitin-protein ligase Midline-1">
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<meta name="citation_keywords" content="MID1">
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<meta name="citation_keywords" content="MID1-Related Opitz G/BBB Syndrome">
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<meta name="DC.Title" content="MID1-Related Opitz G/BBB Syndrome">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Germana Meroni">
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<meta name="DC.Date" content="2023/10/19">
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<meta name="description" content="MID1-related Opitz G/BBB syndrome (MID1-OS) is characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 30% of affected males. Cleft lip and/or palate are present in approximately half of affected males. Other malformations (present in <50% of affected males) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only.">
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<meta name="og:description" content="MID1-related Opitz G/BBB syndrome (MID1-OS) is characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 30% of affected males. Cleft lip and/or palate are present in approximately half of affected males. Other malformations (present in <50% of affected males) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1327_"><span class="title" itemprop="name"><i>MID1</i>-Related Opitz G/BBB Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: X-Linked Opitz Syndrome (XLOS), X-Linked Opitz G/BBB Syndrome</div><p class="contribs">Meroni G.</p><p class="fm-aai"><a href="#_NBK1327_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 21 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="opitz.Summary" itemprop="description"><h2 id="_opitz_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>MID1</i>-related Opitz G/BBB syndrome (<i>MID1</i>-OS) is characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 30% of affected males. Cleft lip and/or palate are present in approximately half of affected males. Other malformations (present in <50% of affected males) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>MID1</i>-OS is established in a male proband with suggestive findings and a hemizygous pathogenic variant in <i>MID1</i> identified by molecular genetic testing. Females with a heterozygous <i>MID1</i> pathogenic variant usually have isolated hypertelorism and only rarely present with other manifestations of <i>MID1</i>-OS.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management of anomalies by a multidisciplinary team; surgical treatment of cleft lip/palate and other craniofacial anomalies; standard treatments for hearing loss including PE tubes; speech therapy; standard dental treatments as needed for hypodontia; standard surgical management of hypospadias; surgical treatment for medically significant laryngotracheoesophageal abnormalities; anti-reflux therapy as needed; neuropsychological and educational support; surgical repair of congenital heart defects and imperforate anus; surgical treatment and/or refractive lenses as needed per ophthalmologist.</p><p><i>Surveillance:</i> Follow up with craniofacial team for cleft lip/palate care; audiology evaluation annually or as needed; follow up with urologist as needed for those with significant hypospadias and/or other urinary tract defects; gastroenterology, pulmonology, and/or surgical team follow up for those with laryngotracheoesophageal defects; monitor developmental and educational needs at each visit; cardiology follow up per cardiologist; gastroenterology follow up as recommended for anal defects; ophthalmology evaluations as recommend by ophthalmologist; assess psychosocial and care coordination needs at each visit.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>MID1</i>-OS is inherited in an X-linked manner. In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. If the mother of the proband has an <i>MID1</i> pathogenic variant, the chance of transmitting it in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygotes and will usually manifest hypertelorism only. Once the <i>MID1</i> pathogenic variant has been identified in an affected family member, heterozygote testing for at-risk female relatives and prenatal and preimplantation genetic testing are possible.</p></div></div><div id="opitz.Diagnosis"><h2 id="_opitz_Diagnosis_">Diagnosis</h2><p>For the purposes of this <i>GeneReview</i>, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care [<a class="bibr" href="#opitz.REF.caughey.2021.1953" rid="opitz.REF.caughey.2021.1953">Caughey et al 2021</a>].</p><div id="opitz.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>MID1</i>-related Opitz G/BBB syndrome (<i>MID1</i>-OS) <b>should be suspected</b> in a male with the following clinical and imaging findings and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Hypertelorism and/or telecanthus (present in virtually all affected individuals)</div></li><li class="half_rhythm"><div>Hypospadias</div></li><li class="half_rhythm"><div>Laryngotracheoesophageal abnormalities, primarily laryngeal cleft, resulting in swallowing difficulties and respiratory dysfunction</div></li><li class="half_rhythm"><div>Cleft lip and/or palate</div></li><li class="half_rhythm"><div>Intellectual disability and developmental delay</div></li><li class="half_rhythm"><div>Congenital heart defects (e.g., ventricular septal defect, atrial septal defect, persistent left superior vena cava, patent ductus arteriosus)</div></li><li class="half_rhythm"><div>Imperforate or ectopic anus</div></li></ul><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div>Urinary tract abnormalities including vesicoureteral reflux and hydronephrosis</div></li><li class="half_rhythm"><div>Midline defects of the brain including agenesis of the corpus callosum and cerebellar vermis agenesis or hypoplasia</div></li></ul><p><b>Family history</b> is consistent with X-linked inheritance (e.g., no male-to-male transmission). Absence of a known family history does not preclude the diagnosis.</p></div><div id="opitz.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Male proband.</b> The diagnosis of <i>MID1</i>-OS <b>is established</b> in a male proband with <a href="#opitz.Suggestive_Findings">suggestive findings</a> and a hemizygous pathogenic (or likely pathogenic) variant in <i>MID1</i> identified by molecular genetic testing (see <a href="/books/NBK1327/table/opitz.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobopitzTmoleculargenetictestingusedi">Table 1</a>).</p><p><b>Female proband.</b> Females with a heterozygous <i>MID1</i> pathogenic (or likely pathogenic) variant usually have isolated hypertelorism and only rarely present with other manifestations of <i>MID1</i>-OS.</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#opitz.REF.richards.2015.405" rid="opitz.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include likely pathogenic variants. (2) Identification of a hemizygous or heterozygous <i>MID1</i> variant of uncertain significance does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#opitz.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#opitz.Option_2">Option 2</a>).</p><div id="opitz.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>MID1</i> is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, 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 deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</p><p><b>A multigene panel</b> that includes <i>MID1</i> and other genes of interest (see <a href="#opitz.Differential_Diagnosis">Differential Diagnosis</a>) may be considered to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity 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>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="opitz.Option_2"><h4>Option 2</h4><p>When the diagnosis of <i>MID1</i>-OS is not considered because an individual has atypical phenotypic features, <b>comprehensive genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTmoleculargenetictestingusedi"><a href="/books/NBK1327/table/opitz.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobopitzTmoleculargenetictestingusedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.molecular_genetic_testing_used_i"><a href="/books/NBK1327/table/opitz.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobopitzTmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>MID1</i>-Related Opitz G/BBB Syndrome </p></div></div></div></div></div><div id="opitz.Clinical_Characteristics"><h2 id="_opitz_Clinical_Characteristics_">Clinical Characteristics</h2><div id="opitz.Clinical_Description"><h3>Clinical Description</h3><p><i>MID1</i>-related Opitz G/BBB syndrome (<i>MID1</i>-OS) is characterized by facial anomalies, genitourinary abnormalities, laryngotracheoesophageal defects, and congenital heart defects. Developmental delay and intellectual disability are common. Clinical manifestations are most evident in affected males, although wide clinical variability has been described, even among members of the same family. To date, 90 individuals have been identified with a pathogenic variant in <i>MID1</i> and are reported together with their clinical synopsis [<a class="bibr" href="#opitz.REF.gaudenz.1998.703" rid="opitz.REF.gaudenz.1998.703">Gaudenz et al 1998</a>, <a class="bibr" href="#opitz.REF.cox.2000.2553" rid="opitz.REF.cox.2000.2553">Cox et al 2000</a>, <a class="bibr" href="#opitz.REF.de_falco.2003.222" rid="opitz.REF.de_falco.2003.222">De Falco et al 2003</a>, <a class="bibr" href="#opitz.REF.winter.2003.249" rid="opitz.REF.winter.2003.249">Winter et al 2003</a>, <a class="bibr" href="#opitz.REF.pinson.2004.381" rid="opitz.REF.pinson.2004.381">Pinson et al 2004</a>, <a class="bibr" href="#opitz.REF.so.2005.1" rid="opitz.REF.so.2005.1">So et al 2005</a>, <a class="bibr" href="#opitz.REF.mnayer.2006.198" rid="opitz.REF.mnayer.2006.198">Mnayer et al 2006</a>, <a class="bibr" href="#opitz.REF.ferrentino.2007.206" rid="opitz.REF.ferrentino.2007.206">Ferrentino et al 2007</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.hu.2012.726" rid="opitz.REF.hu.2012.726">Hu et al 2012</a>, <a class="bibr" href="#opitz.REF.h_ning.2013.188" rid="opitz.REF.h_ning.2013.188">Hüning et al 2013</a>, <a class="bibr" href="#opitz.REF.migliore.2013.404" rid="opitz.REF.migliore.2013.404">Migliore et al 2013</a>, <a class="bibr" href="#opitz.REF.ji.2014.140" rid="opitz.REF.ji.2014.140">Ji et al 2014</a>, <a class="bibr" href="#opitz.REF.li.2015.95" rid="opitz.REF.li.2015.95">Li et al 2015</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017,</a>
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<a class="bibr" href="#opitz.REF.pereacabrera.2023.e2234" rid="opitz.REF.pereacabrera.2023.e2234">Perea-Cabrera et al 2023</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTmid1relatedopitzgbbbsyndrome"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.mid1related_opitz_gbbb_syndrome"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>MID1</i>-Related Opitz G/BBB Syndrome: Frequency of Select Features in Males </p></div></div><div id="opitz.Affected_Males"><h4>Affected Males</h4><p><b>Facial appearance and head anomalies.</b> The facial appearance of affected males is characterized by large fontanelle, prominent metopic suture, prominent forehead, widow's peak, hypertelorism (which can also be accompanied by telecanthus), a broad nasal bridge, anteverted nares, and low-set and malformed ears. Unilateral or bilateral cleft lip and/or palate is present in approximately half of affected males. Feeding issues and hearing impairment can be present due to cleft lip/palate. Other oral manifestations include high-arched palate, ankyloglossia, micrognathia, hypodontia, and neonatal teeth [<a class="bibr" href="#opitz.REF.robin.1996.305" rid="opitz.REF.robin.1996.305">Robin et al 1996</a>, <a class="bibr" href="#opitz.REF.shaw.2006.185" rid="opitz.REF.shaw.2006.185">Shaw et al 2006</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017</a>].</p><p><b>Urogenital abnormalities.</b> Hypospadias of varying severity is present in approximately 90% of males with <i>MID1</i>-OS and is often associated with other genital anomalies such as cryptorchidism and hypoplastic/bifid scrotum. Severe hypospadias can be associated with urinary tract dysfunction (e.g., vesicoureteral reflux, hydronephrosis) [<a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017</a>].</p><p><b>Laryngotracheoesophageal (LTE) defects</b> may result in coughing and choking with feeding, recurrent pneumonia, and life-threatening aspiration. In their most severe form, LTE defects manifest as laryngeal and tracheoesophageal clefts and in the milder form as tracheoesophageal fistulae or LTE dysmotility. The incidence of respiratory and/or gastroesophageal symptoms is probably underestimated because mildly affected individuals may only have functional swallowing difficulties that improve with age and eventually disappear during infancy [<a class="bibr" href="#opitz.REF.pinson.2004.381" rid="opitz.REF.pinson.2004.381">Pinson et al 2004</a>].</p><p><b>Neurologic findings.</b> Almost one third of individuals with <i>MID1</i>-OS show developmental delay and intellectual disability; they frequently manifest delay in onset of walking, short attention span, learning difficulties, and speech problems. In some individuals, these delays are secondary to surgical interventions.</p><p>Midline brain anatomic defects including agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis and Dandy-Walker malformations were identified in about half of males with an <i>MID1</i> pathogenic variant who underwent MRI examination [<a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>].</p><p><b>Congenital heart disease.</b> Approximately 24% of males with <i>MID1</i>-OS present with congenital heart anomalies (e.g., ventricular septal defect, atrial septal defect, coarctation of the aorta, persistent left superior vena cava, patent ductus arteriosus, patent foramen ovale, and total anomalous pulmonary venous connection [<a class="bibr" href="#opitz.REF.pereacabrera.2023.e2234" rid="opitz.REF.pereacabrera.2023.e2234">Perea-Cabrera et al 2023</a>].</p><p><b>Anal abnormalities</b> are present in 22% of males with <i>MID1</i>-OS (e.g., imperforate anus, ectopic anus) [<a class="bibr" href="#opitz.REF.robin.1996.305" rid="opitz.REF.robin.1996.305">Robin et al 1996</a>, <a class="bibr" href="#opitz.REF.de_falco.2003.222" rid="opitz.REF.de_falco.2003.222">De Falco et al 2003</a>, <a class="bibr" href="#opitz.REF.pinson.2004.381" rid="opitz.REF.pinson.2004.381">Pinson et al 2004</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017</a>, <a class="bibr" href="#opitz.REF.pereacabrera.2023.e2234" rid="opitz.REF.pereacabrera.2023.e2234">Perea-Cabrera et al 2023</a>].</p><p><b>Ophthalmologic features.</b> Refractive error and strabismus have been reported.</p></div><div id="opitz.Heterozygous_Females"><h4>Heterozygous Females</h4><p>Heterozygous females usually have hypertelorism only, and rarely other manifestations (e.g., characteristic facial features [anteverted nares, short nose, short uvula, high arched palate, micrognathia], tracheoesophageal cleft or esophageal stenosis, anal malformations) [<a class="bibr" href="#opitz.REF.so.2005.1" rid="opitz.REF.so.2005.1">So et al 2005</a>, <a class="bibr" href="#opitz.REF.pereacabrera.2023.e2234" rid="opitz.REF.pereacabrera.2023.e2234">Perea-Cabrera et al 2023</a>].</p></div></div><div id="opitz.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>In general, no genotype-phenotype correlations have been observed. Pathogenic missense, nonsense, splice site, and frameshift variants, insertions, and deletions all result in highly variable phenotypes even within the same family [<a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017</a>].</p><p>Two possible exceptions are:</p><ul><li class="half_rhythm"><div>An association between truncating variants and the presence of anatomic brain abnormalities, in particular cerebellar defects [<a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>];</div></li><li class="half_rhythm"><div>Possible correlation of a mild phenotype with pathogenic variants in the fibronectin type III domain of the protein [<a class="bibr" href="#opitz.REF.mnayer.2006.198" rid="opitz.REF.mnayer.2006.198">Mnayer et al 2006</a>].</div></li></ul></div><div id="opitz.Penetrance"><h3>Penetrance</h3><p>Usually, the presence of an <i>MID1</i> pathogenic variant is associated with clinical findings of <i>MID1</i>-OS.</p></div><div id="opitz.Nomenclature"><h3>Nomenclature</h3><p>The title of this <i>GeneReview</i>, <i>MID1</i>-related Opitz G/BBB syndrome, is based on the dyadic naming approach proposed by <a class="bibr" href="#opitz.REF.biesecker.2021.8" rid="opitz.REF.biesecker.2021.8">Biesecker et al [2021]</a>, in which mendelian disorders are designated by combining the mutated gene and resulting phenotype.</p><p>Opitz G/BBB syndrome was first reported as two separate entities, BBB syndrome [<a class="bibr" href="#opitz.REF.opitz.b" rid="opitz.REF.opitz.b">Opitz et al 1969b</a>] and G syndrome [<a class="bibr" href="#opitz.REF.opitz.a" rid="opitz.REF.opitz.a">Opitz et al 1969a</a>]. Subsequently, it became apparent that the two syndromes identified in 1969 are in fact a single entity, now named Opitz G/BBB syndrome.</p><p>Other names, no longer used, include hypospadias-dysphagia syndrome, Opitz-Frias syndrome, telecanthus with associated abnormalities, and hypertelorism-hypospadias syndrome.</p><p>Of note, <i>MID1</i>-OS is distinct from autosomal dominant Opitz G/BBB syndrome.</p></div></div><div id="opitz.Genetically_Related_Allelic_Disord"><h2 id="_opitz_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No other phenotype is known to be associated with pathogenic variants in <i>MID1</i>.</p></div><div id="opitz.Differential_Diagnosis"><h2 id="_opitz_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTgenesofinterestinthediffere"><a href="/books/NBK1327/table/opitz.T.genes_of_interest_in_the_differe/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobopitzTgenesofinterestinthediffere"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.genes_of_interest_in_the_differe"><a href="/books/NBK1327/table/opitz.T.genes_of_interest_in_the_differe/?report=objectonly" target="object" rid-ob="figobopitzTgenesofinterestinthediffere">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of <i>MID1</i>-Related Opitz G/BBB Syndrome </p></div></div></div><div id="opitz.Management"><h2 id="_opitz_Management_">Management</h2><div id="opitz.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>MID1</i>-related Opitz G/BBB syndrome (<i>MID1</i>-OS), the evaluations summarized in <a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_1/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome1">Table 4</a> by a multidisciplinary team (including craniofacial surgeon, ophthalmologist, pediatrician, pediatric urologist, cardiologist, pulmonologist, speech-language pathologist, and clinical geneticist) are recommended if they have not already been performed.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTmid1relatedopitzgbbbsyndrome1"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_1/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.mid1related_opitz_gbbb_syndrome_1"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_1/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome1">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>MID1</i>-Related Opitz G/BBB Syndrome: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="opitz.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves management of anomalies by a multidisciplinary team (including craniofacial surgeon, ophthalmologist, pediatrician, pediatric urologist, cardiologist, pulmonologist, speech-language pathologist, and clinical geneticist) to help assure coordination of care (see <a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_2/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome2">Table 5</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTmid1relatedopitzgbbbsyndrome2"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_2/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.mid1related_opitz_gbbb_syndrome_2"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_2/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome2">Table 5. </a></h4><p class="float-caption no_bottom_margin"><i>MID1</i>-Related Opitz G/BBB Syndrome: Treatment of Manifestations </p></div></div></div><div id="opitz.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_3/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome3">Table 6</a> are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzTmid1relatedopitzgbbbsyndrome3"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_3/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.T.mid1related_opitz_gbbb_syndrome_3"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_3/?report=objectonly" target="object" rid-ob="figobopitzTmid1relatedopitzgbbbsyndrome3">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>MID1</i>-Related Opitz G/BBB Syndrome: Recommended Surveillance </p></div></div></div><div id="opitz.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#opitz.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="opitz.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="opitz.Genetic_Counseling"><h2 id="_opitz_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="opitz.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>MID1</i>-related Opitz G/BBB syndrome (<i>MID1</i>-OS) is inherited in an X-linked manner.</p></div><div id="opitz.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a male proband</b>
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</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disorder, nor will he be hemizygous for the <i>MID1</i> pathogenic variant; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. Note: If a woman has more than one affected child and no other affected relatives and if the <i>MID1</i> pathogenic variant cannot be detected in her leukocyte DNA, she most likely has germline mosaicism.</div></li><li class="half_rhythm"><div>If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote, the affected male may have a <i>de novo</i>
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<i>MID1</i> pathogenic variant (in which case the mother is not a heterozygote), or the mother may have somatic/germline mosaicism. <i>De novo</i> pathogenic variants have been detected in several affected males [<a class="bibr" href="#opitz.REF.pinson.2004.381" rid="opitz.REF.pinson.2004.381">Pinson et al 2004</a>, <a class="bibr" href="#opitz.REF.ferrentino.2007.206" rid="opitz.REF.ferrentino.2007.206">Ferrentino et al 2007</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al 2017</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing of the mother is recommended to confirm her genetic status and to allow reliable recurrence risk assessment.</div></li></ul><p><b>Sibs of a male proband.</b> The risk to sibs depends on the genetic status of the mother:</p><ul><li class="half_rhythm"><div>If the mother of the proband has an <i>MID1</i> pathogenic variant, the chance of transmitting it in each pregnancy is 50%.</div><ul><li class="half_rhythm"><div>Males who inherit the pathogenic variant will be affected. (Note: Wide variability in clinical manifestations has been described among affected members of the same family.)</div></li><li class="half_rhythm"><div>Females who inherit the pathogenic variant will be heterozygotes and will usually manifest hypertelorism only (see Clinical Description, <a href="#opitz.Heterozygous_Females">Heterozygous Females</a>).</div></li></ul></li><li class="half_rhythm"><div>If the proband represents a simplex case and if the <i>MID1</i> pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but slightly greater than that of the general population because of the possibility of maternal germline mosaicism.</div></li></ul><p><b>Offspring of a male proband.</b> Mildly affected males transmit the <i>MID1</i> pathogenic variant to:</p><ul><li class="half_rhythm"><div>All of their daughters, who will be heterozygotes and will usually manifest hypertelorism only;</div></li><li class="half_rhythm"><div>None of their sons.</div></li></ul><p><b>Other family members.</b> The maternal aunts and maternal cousins of a male proband may be at risk of having an <i>MID1</i> pathogenic variant.</p><p>Note: Molecular genetic testing may be able to identify the family member in whom a <i>de novo</i> pathogenic variant arose, information that could help determine genetic risk status of the extended family.</p></div><div id="opitz.Heterozygote_Detection"><h3>Heterozygote Detection</h3><p>Heterozygote testing for at-risk female relatives requires prior identification of the <i>MID1</i> pathogenic variant in the family.</p><p>Note: Females who are heterozygous for this X-linked disorder will usually manifest hypertelorism only.</p></div><div id="opitz.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are heterozygotes, or are at risk of being heterozygotes.</div></li></ul></div><div id="opitz.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>MID1</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. 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="opitz.Resources"><h2 id="_opitz_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/opitz-g-bbb-syndrome/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Opitz G/BBB syndrome</a>
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</div></li><li class="half_rhythm"><div>
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<b>American Cleft Palate-Craniofacial Association</b>
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</div><div><b>Phone:</b> 919-933-9044</div><div>
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<a href="https://acpa-cpf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">acpa-cpf.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Face Equality International</b>
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</div><div>United Kingdom</div><div>
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<a href="https://faceequalityinternational.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">faceequalityinternational.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Medline Plus</b>
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</div><div>
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<a href="http://www.nlm.nih.gov/medlineplus/ency/article/003000.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hypospadias repair</a>
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</div></li></ul>
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</div><div id="opitz.Molecular_Genetics"><h2 id="_opitz_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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzmolgenTA"><a href="/books/NBK1327/table/opitz.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobopitzmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.molgen.TA"><a href="/books/NBK1327/table/opitz.molgen.TA/?report=objectonly" target="object" rid-ob="figobopitzmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">MID1-Related Opitz G/BBB Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figopitzmolgenTB"><a href="/books/NBK1327/table/opitz.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobopitzmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="opitz.molgen.TB"><a href="/books/NBK1327/table/opitz.molgen.TB/?report=objectonly" target="object" rid-ob="figobopitzmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for MID1-Related Opitz G/BBB Syndrome (View All in OMIM) </p></div></div><div id="opitz.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>MID1</i> is composed of nine coding exons and variable and alternative 5' untranslated regions [<a class="bibr" href="#opitz.REF.quaderi.1997.285" rid="opitz.REF.quaderi.1997.285">Quaderi et al 1997</a>, <a class="bibr" href="#opitz.REF.gaudenz.1998.703" rid="opitz.REF.gaudenz.1998.703">Gaudenz et al 1998</a>, <a class="bibr" href="#opitz.REF.perry.1998.299" rid="opitz.REF.perry.1998.299">Perry et al 1998</a>, <a class="bibr" href="#opitz.REF.van_den_veyver.1998.251" rid="opitz.REF.van_den_veyver.1998.251">Van den Veyver et al 1998</a>, <a class="bibr" href="#opitz.REF.cox.2000.2553" rid="opitz.REF.cox.2000.2553">Cox et al 2000</a>, <a class="bibr" href="#opitz.REF.landry.2002.499" rid="opitz.REF.landry.2002.499">Landry & Mager 2002</a>]. <i>MID1</i> encodes E3 ubiquitin-protein ligase Midline-1, which is anchored to the microtubules [<a class="bibr" href="#opitz.REF.cainarca.1999.1387" rid="opitz.REF.cainarca.1999.1387">Cainarca et al 1999</a>, <a class="bibr" href="#opitz.REF.schweiger.1999.2794" rid="opitz.REF.schweiger.1999.2794">Schweiger et al 1999</a>, <a class="bibr" href="#opitz.REF.cox.2000.2553" rid="opitz.REF.cox.2000.2553">Cox et al 2000</a>] and acts as an E3 ubiquitin ligase that regulates the degradation of phosphatase 2A [<a class="bibr" href="#opitz.REF.liu.2001.6650" rid="opitz.REF.liu.2001.6650">Liu et al 2001</a>, <a class="bibr" href="#opitz.REF.trockenbacher.2001.287" rid="opitz.REF.trockenbacher.2001.287">Trockenbacher et al 2001</a>, <a class="bibr" href="#opitz.REF.short.2002.1" rid="opitz.REF.short.2002.1">Short et al 2002</a>]. The role of this protein function within the cell and during development is yet to be fully clarified, and possible roles in common non-genetic diseases have also been reported; the findings available are reviewed in <a class="bibr" href="#opitz.REF.baldini.2020.144655" rid="opitz.REF.baldini.2020.144655">Baldini et al [2020]</a>.</p><p>The pathogenic variants are missense and nonsense variants, small deletions, intronic splicing variants, or insertions located along the entire length of the gene – the majority in the most 3' portion of the gene. <i>MID1</i> whole-gene deletions as well as single-exon deletions and duplications have been reported [<a class="bibr" href="#opitz.REF.winter.2003.249" rid="opitz.REF.winter.2003.249">Winter et al 2003</a>, <a class="bibr" href="#opitz.REF.ferrentino.2007.206" rid="opitz.REF.ferrentino.2007.206">Ferrentino et al 2007</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>, <a class="bibr" href="#opitz.REF.h_ning.2013.188" rid="opitz.REF.h_ning.2013.188">Hüning et al 2013</a>, <a class="bibr" href="#opitz.REF.migliore.2013.404" rid="opitz.REF.migliore.2013.404">Migliore et al 2013</a>, <a class="bibr" href="#opitz.REF.micale.2023.1208" rid="opitz.REF.micale.2023.1208">Micale et al 2023</a>].</p><p><b>Mechanism of disease causation.</b> The missense and truncated forms lower their affinity for the microtubular apparatus. The pathogenic mechanism is likely to be caused by the loss of E3 ubiquitin-protein ligase Midline-1 function on the microtubules.</p></div></div><div id="opitz.Chapter_Notes"><h2 id="_opitz_Chapter_Notes_">Chapter Notes</h2><div id="opitz.Author_Notes"><h3>Author Notes</h3><p><b>Germana Meroni, PhD,</b> focuses on basic research on the molecular basis of X-linked Opitz syndrome, including functional studies of <i>MID1</i> and proteins belonging to the TRIM/RBCC family.</p><p>Contact Dr Meroni to inquire about review of <i>MID1</i> variants of uncertain significance.</p></div><div id="opitz.Acknowledgments"><h3>Acknowledgments</h3><p>This chapter is dedicated to the memory of Dr John M Opitz, whose passion and dedication for children and families affected by <i>MID1</i>-related Opitz G/BBB syndrome has inspired the work of many geneticists, including Dr Germana Meroni.</p></div><div id="opitz.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>19 October 2023 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 April 2018 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>28 July 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>18 January 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>17 December 2004 (me) Review posted live</div></li><li class="half_rhythm"><div>30 June 2004 (gm) Original submission</div></li></ul></div></div><div id="opitz.References"><h2 id="_opitz_References_">References</h2><div id="opitz.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.baldini.2020.144655">Baldini
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R, Mascaro
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M, Meroni
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G.
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The MID1 gene product in physiology and disease.
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Gene.
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2020;747:144655.
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[<a href="/pmc/articles/PMC8011326/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8011326</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32283114" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32283114</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.biesecker.2021.8">Biesecker
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LG, Adam
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MP, Alkuraya
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FS, Amemiya
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AR, Bamshad
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MJ, Beck
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AE, Bennett
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JT, Bird
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LM, Carey
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JC, Chung
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B, Clark
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RD, Cox
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TC, Curry
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C, Dinulos
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MBP, Dobyns
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WB, Giampietro
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PF, Girisha
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KM, Glass
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IA, Graham
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JM
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Jr, Gripp
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KW, Haldeman-Englert
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CR, Hall
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BD, Innes
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AM, Kalish
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JM, Keppler-Noreuil
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KM, Kosaki
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K, Kozel
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BA, Mirzaa
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GM, Mulvihill
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JJ, Nowaczyk
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MJM, Pagon
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RA, Retterer
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K, Rope
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AF, Sanchez-Lara
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PA, Seaver
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LH, Shieh
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JT, Slavotinek
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AM, Sobering
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AK, Stevens
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CA, Stevenson
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DA, Tan
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TY, Tan
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WH, Tsai
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AC, Weaver
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DD, Williams
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MS, Zackai
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E, Zarate
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YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics.
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Am J Hum Genet.
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2021;108:8-15.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/16760742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16760742</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.short.2002.1">Short
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KM, Hopwood
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B, Yi
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Z, Cox
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TC. MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, Alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders.
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BMC Cell Biol.
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2002;3:1
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[<a href="/pmc/articles/PMC64779/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC64779</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11806752" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11806752</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.so.2005.1">So
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J, Suckow
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V, Kijas
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Z, Kalscheuer
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V, Moser
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B, Winter
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J, Baars
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M, Firth
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H, Lunt
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P, Hamel
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B, Meinecke
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P, Moraine
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C, Odent
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S, Schinzel
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A, van der Smagt
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JJ, Devriendt
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K, Albrecht
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B, Gillessen-Kaesbach
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G, van der Burgt
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I, Petrij
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F, Faivre
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L, McGaughran
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J, McKenzie
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F, Opitz
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JM, Cox
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T, Schweiger
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S. Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations.
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Am J Med Genet A.
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2005;132A:1-7.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/15558842" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15558842</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.stenson.2020.1197">Stenson
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PD, Mort
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M, Ball
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EV, Chapman
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M, Evans
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K, Azevedo
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L, Hayden
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M, Heywood
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S, Millar
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DS, Phillips
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AD, Cooper
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DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting.
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Hum Genet.
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2020;139:1197-207.
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[<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.trockenbacher.2001.287">Trockenbacher
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A, Suckow
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V, Foerster
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J, Winter
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J, Krauss
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S, Ropers
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HH, Schneider
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R, Schweiger
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S. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.
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Nat Genet.
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2001;29:287-94
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[<a href="https://pubmed.ncbi.nlm.nih.gov/11685209" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11685209</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.van_den_veyver.1998.251">Van den Veyver
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IB, Cormier
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TA, Jurecic
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V, Baldini
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A, Zoghbi
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HY. Characterization and physical mapping in human and mouse of a novel RING finger gene in Xp22.
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Genomics.
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1998;51:251-61.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/9722948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9722948</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="opitz.REF.winter.2003.249">Winter
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J, Lehmann
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T, Suckow
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V, Kijas
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Z, Kulozik
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A, Kalscheuer
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V, Hamel
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B, Devriendt
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K, Opitz
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J, Lenzner
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S, Ropers
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HH, Schweiger
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S. Duplication of the MID1 first exon in a patient with Opitz G/BBB syndrome.
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Hum Genet.
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2003;112:249-54
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[<a href="https://pubmed.ncbi.nlm.nih.gov/12545276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12545276</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1327_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Germana Meroni</span>, PhD<div class="affiliation small">Department of Life Sciences<br />University of Trieste<br />Trieste, Italy<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ti.stinu@inoremg" class="oemail">ti.stinu@inoremg</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">December 17, 2004</span>; Last Update: <span itemprop="dateModified">October 19, 2023</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Meroni G. MID1-Related Opitz G/BBB Syndrome. 2004 Dec 17 [Updated 2023 Oct 19]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/cmt2a/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/mirage/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobopitzTmoleculargenetictestingusedi"><div id="opitz.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>MID1</i>-Related Opitz G/BBB Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MID1</i>
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</td><td headers="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90% <sup>4</sup></td></tr><tr><td headers="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_opitz.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10% <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="opitz.TF.1.1"><p class="no_margin">See <a href="/books/NBK1327/?report=reader#opitz.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="opitz.TF.1.2"><p class="no_margin">See <a href="#opitz.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="opitz.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="opitz.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#opitz.REF.stenson.2020.1197" rid="opitz.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="opitz.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="opitz.TF.1.6"><p class="no_margin">Whole-gene deletions have been reported [<a class="bibr" href="#opitz.REF.winter.2003.249" rid="opitz.REF.winter.2003.249">Winter et al 2003</a>, <a class="bibr" href="#opitz.REF.ferrentino.2007.206" rid="opitz.REF.ferrentino.2007.206">Ferrentino et al 2007</a>, <a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al 2008</a>]. In addition, single-exon deletions and duplications have been reported [<a class="bibr" href="#opitz.REF.winter.2003.249" rid="opitz.REF.winter.2003.249">Winter et al 2003</a>, <a class="bibr" href="#opitz.REF.h_ning.2013.188" rid="opitz.REF.h_ning.2013.188">Hüning et al 2013</a>, <a class="bibr" href="#opitz.REF.migliore.2013.404" rid="opitz.REF.migliore.2013.404">Migliore et al 2013</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzTmid1relatedopitzgbbbsyndrome"><div id="opitz.T.mid1related_opitz_gbbb_syndrome" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>MID1</i>-Related Opitz G/BBB Syndrome: Frequency of Select Features in Males</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.mid1related_opitz_gbbb_syndrome_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Males w/Feature</th></tr></thead><tbody><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertelorism</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~100%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypospadias</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laryngotracheoesophageal defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">70%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cleft lip &/or palate</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">48%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intellectual disability &/or developmental delay</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital heart defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">24%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Anal abnormalities</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22%</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain abnormalities</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19/41 <sup>1</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><a class="bibr" href="#opitz.REF.fontanella.2008.584" rid="opitz.REF.fontanella.2008.584">Fontanella et al [2008]</a>, <a class="bibr" href="#opitz.REF.li.2015.95" rid="opitz.REF.li.2015.95">Li et al [2015]</a>, <a class="bibr" href="#opitz.REF.maia.2017.45" rid="opitz.REF.maia.2017.45">Maia et al [2017]</a>, <a class="bibr" href="#opitz.REF.micale.2023.1208" rid="opitz.REF.micale.2023.1208">Micale et al [2023]</a>, <a class="bibr" href="#opitz.REF.pereacabrera.2023.e2234" rid="opitz.REF.pereacabrera.2023.e2234">Perea-Cabrera et al [2023]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="opitz.TF.2.1"><p class="no_margin">Includes males with <i>MID1</i>-related Opitz G/BBB syndrome who have undergone brain MRI examination</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzTgenesofinterestinthediffere"><div id="opitz.T.genes_of_interest_in_the_differe" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of <i>MID1</i>-Related Opitz G/BBB Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.genes_of_interest_in_the_differe/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.genes_of_interest_in_the_differe_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene / Genetic Mechanism</th><th id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Features of This Disorder</th></tr><tr><th headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4" id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<i>MID1</i>-OS</th><th headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4" id="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from <i>MID1</i>-OS</th></tr></thead><tbody><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22q11.2 deletion</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/gr_22q11deletion/?report=reader">22q11.2 deletion syndrome</a> <sup>1</sup></td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Cleft lip/palate</div></li><li class="half_rhythm"><div>Congenital heart defects</div></li><li class="half_rhythm"><div>Laryngotracheoesophageal defects</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Genitourinary defects</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skeletal anomalies</div></li><li class="half_rhythm"><div>Autoimmune disorders</div></li><li class="half_rhythm"><div>Hypotonia, polymicrogyria</div></li></ul>
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</td></tr><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CASK</i>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CASK</i>-related FG syndrome / XL ID ± nystagmus <sup>2</sup> (See <a href="/books/n/gene/cask-dis/?report=reader"><i>CASK </i>Disorders</a>.)</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Cryptorchidism</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Feeding problems</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Joint hyperlaxity</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Hypotonia</div></li></ul>
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</td></tr><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EFNB1</i>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniofrontonasal dysplasia (OMIM <a href="https://omim.org/entry/304110" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">304110</a>)</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Cleft lip/palate</div></li><li class="half_rhythm"><div>Hypospadias</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Hypoplasia or agenesis of corpus callosum</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Skeletal, chest, skin, nail, & hair defects</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Hypotonia</div></li></ul>
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</td></tr><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MED12</i>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MED12-</i>related FG syndrome (See <a href="/books/n/gene/fg/?report=reader"><i>MED12</i>-Related Disorders</a>.)</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Congenital heart defects</div></li><li class="half_rhythm"><div>Cryptorchidism</div></li><li class="half_rhythm"><div>DD/ID</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Congenital hypotonia w/joint hyperlaxity evolving into spasticity</div></li><li class="half_rhythm"><div>Chronic constipation</div></li><li class="half_rhythm"><div>Characteristic behavior (affable & eager to please)</div></li></ul>
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</td></tr><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SPECC1L</i>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SPECC1L</i> syndrome <sup>3</sup> (also referred to as AD Opitz G/BBB syndrome & Teebi hypertelorism syndrome 1 [OMIM <a href="https://omim.org/entry/145420" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">145420</a>])</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Cleft lip/palate</div></li><li class="half_rhythm"><div>Congenital heart defects</div></li><li class="half_rhythm"><div>DD/ID</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Congenital diaphragmatic hernias</div></li><li class="half_rhythm"><div>Bicornuate uterus</div></li><li class="half_rhythm"><div>Absence of hypospadias</div></li></ul>
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</td></tr><tr><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ZEB2</i>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mws/?report=reader">Mowat-Wilson syndrome</a>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Cardiovascular defects</div></li><li class="half_rhythm"><div>Hypospadias</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Hypoplasia or agenesis of corpus callosum</div></li></ul>
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</td><td headers="hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_1_4 hd_h_opitz.T.genes_of_interest_in_the_differe_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ocular & gastrointestinal abnormalities</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Pectus excavatum</div></li><li class="half_rhythm"><div>Hypotonia</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="opitz.TF.3.1"><p class="no_margin">It is now recognized that 22q11.2 deletion syndrome encompasses the phenotypes previously described as DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, some cases of autosomal dominant Opitz G/BBB syndrome, and Cayler cardiofacial syndrome (see <a href="/books/n/gene/gr_22q11deletion/?report=reader">22q11.2 Deletion Syndrome</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="opitz.TF.3.2"><p class="no_margin">An FG syndrome (FGS)-like phenotype has been suggested as a distinct <i>CASK</i>-related phenotype based on findings in affected males from two families (see <a href="/books/n/gene/cask-dis/?report=reader"><i>CASK</i> Disorders</a>). However, with the exception of <i>MED12-</i>related FGS, FGS is not clearly defined, and <i>CASK</i>-related FGS is not discernible as a phenotype. Thus, it seems more appropriate to subsume the phenotype described in these families under X-linked intellectual disability with or without nystagmus.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="opitz.TF.3.3"><p class="no_margin">
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<a class="bibr" href="#opitz.REF.bhoj.2019.103588" rid="opitz.REF.bhoj.2019.103588">Bhoj et al [2019]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzTmid1relatedopitzgbbbsyndrome1"><div id="opitz.T.mid1related_opitz_gbbb_syndrome_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>MID1</i>-Related Opitz G/BBB Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.mid1related_opitz_gbbb_syndrome_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>General</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Past medical history & physical exam w/attention to palate, heart, genitourinary system, & lower respiratory system</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft lip &/or palate</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral of persons w/cleft lip/palate to craniofacial surgeon</div></li><li class="half_rhythm"><div>Assessment of feeding & speech</div></li><li class="half_rhythm"><div>Dental assessment</div></li></ul>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Audiology eval in those at risk for hearing loss due to cleft lip/palate</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Urogenital abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of hypospadias by urologist, incl ultrasound exam to evaluate for urinary tract dysfunction in males w/severe hypospadias</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>LTE defects</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laryngoscopy & chest x-ray in persons who have choking w/feeding, recurrent pneumonia, &/or aspiration</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental delay</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental eval</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Congenital heart disease</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anal abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of anal position & patency</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic manifestations</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete ophthalmology eval incl assessment of visual acuity, refractive error, & ocular alignment for possible strabismus</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>MID1</i>-OS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By clinicians, wider care team, & family support organizations</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#opitz.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>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">LTE = laryngotracheoesophageal; <i>MID1</i>-OS = <i>MID1</i>-related Opitz G/BBB syndrome; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="opitz.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzTmid1relatedopitzgbbbsyndrome2"><div id="opitz.T.mid1related_opitz_gbbb_syndrome_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>MID1</i>-Related Opitz G/BBB Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.mid1related_opitz_gbbb_syndrome_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft lip &/or palate</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Surgical mgmt for cleft lip/palate & other craniofacial anomalies</div></li><li class="half_rhythm"><div>Standard treatments for hearing loss incl PE tubes for recurrent otitis</div></li><li class="half_rhythm"><div>Speech therapy for speech problems secondary to cleft lip/palate</div></li><li class="half_rhythm"><div>Standard dental treatments as needed for hypodontia</div></li></ul>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Urogenital abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical intervention as needed for hypospadias</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>LTE defects</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Surgical treatment of medically significant LTE abnormalities</div></li><li class="half_rhythm"><div>Anti-reflux pharmacologic therapy minimizes risk for aspiration until laryngeal competence is assured.</div></li></ul>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Often tracheostomy is necessary initially to assure an adequate airway.</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychological & educational support</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many males w/<i>MID1</i>-OS require special educational programs.</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Congenital heart disease</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair as needed for congenital heart defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anal abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical intervention for imperforate anus</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic manifestations</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical treatment as needed by an ophthalmologist &/or refractive lenses</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">LTE = laryngotracheoesophageal; PE = pressure equalization</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzTmid1relatedopitzgbbbsyndrome3"><div id="opitz.T.mid1related_opitz_gbbb_syndrome_3" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>MID1</i>-Related Opitz G/BBB Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.T.mid1related_opitz_gbbb_syndrome_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.T.mid1related_opitz_gbbb_syndrome_3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft lip/palate</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniofacial team follow up for those w/cleft lip/palate</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per craniofacial specialists</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as needed</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Urogenital abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urology follow up for those w/significant hypospadias &/or other urinary tract abnormalities</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per urologist &/or nephrologist</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>LTE defects</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology, pulmonology, &/or surgical team follow up for those w/LTE defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitoring of developmental progress & educational needs</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_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_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Congenital heart disease</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac follow up for those w/cardiac defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per cardiologist</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anal abnormalities</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology &/or surgical follow up for those w/anal defects</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per gastroenterologist or surgical team</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic manifestations</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology assessment</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per ophthalmologist</td></tr><tr><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/Community</b>
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</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).</td><td headers="hd_h_opitz.T.mid1related_opitz_gbbb_syndrome_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">LTE = laryngotracheoesophageal</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzmolgenTA"><div id="opitz.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>MID1-Related Opitz G/BBB Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1327/table/opitz.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_opitz.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_opitz.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_opitz.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_opitz.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_opitz.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_opitz.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_opitz.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/4281" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>MID1</i>
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</a>
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</td><td headers="hd_b_opitz.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=4281" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Xp22<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_b_opitz.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/O15344" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">E3 ubiquitin-protein ligase Midline-1</a>
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</td><td headers="hd_b_opitz.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.LOVD.nl/MID1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MID1 @ LOVD</a>
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</td><td headers="hd_b_opitz.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=MID1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MID1</a>
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</td><td headers="hd_b_opitz.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MID1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MID1</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="opitz.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus 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/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobopitzmolgenTB"><div id="opitz.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for MID1-Related Opitz G/BBB Syndrome (<a href="/omim/300000,300552" 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/NBK1327/table/opitz.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__opitz.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/300000" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300000</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OPITZ GBBB SYNDROME; GBBB</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/300552" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">300552</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MIDLINE 1; MID1</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.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></div></div>
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