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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2024/03/07" /><meta name="citation_author" content="Ebba Alkhunaizi" /><meta name="citation_author" content="David Chitayat" /><meta name="citation_pmid" content="34499436" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK573670/" /><meta name="citation_keywords" content="Protein phosphatase 1 regulatory subunit 12A" /><meta name="citation_keywords" content="PPP1R12A" /><meta name="citation_keywords" content="PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Ebba Alkhunaizi" /><meta name="DC.Contributor" content="David Chitayat" /><meta name="DC.Date" content="2024/03/07" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK573670/" /><meta name="description" content="Individuals with PPP1R12A-related urogenital and/or brain malformation syndrome (UBMS) usually present with multiple congenital anomalies, most commonly involving the brain and/or urogenital systems. The brain abnormalities are variable, with the most severe belonging to the holoprosencephaly spectrum and associated with moderate-to-profound intellectual disability, seizures, and feeding difficulties. In individuals without brain involvement, variable degrees of developmental delay and/or intellectual disability may be present, although normal intelligence has been seen in a minority of affected individuals. Eye (strabismus, microphthalmia/anophthalmia) and skeletal abnormalities (kyphoscoliosis, joint contractures) can also be present in affected individuals of either sex. Regardless of the presence of a brain malformation, affected individuals with a 46,XY chromosome complement may have a difference of sex development (DSD) with gonadal dysgenesis associated with ambiguous genitalia or phenotypic female genitalia." /><meta name="og:title" content="PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Individuals with PPP1R12A-related urogenital and/or brain malformation syndrome (UBMS) usually present with multiple congenital anomalies, most commonly involving the brain and/or urogenital systems. The brain abnormalities are variable, with the most severe belonging to the holoprosencephaly spectrum and associated with moderate-to-profound intellectual disability, seizures, and feeding difficulties. In individuals without brain involvement, variable degrees of developmental delay and/or intellectual disability may be present, although normal intelligence has been seen in a minority of affected individuals. Eye (strabismus, microphthalmia/anophthalmia) and skeletal abnormalities (kyphoscoliosis, joint contractures) can also be present in affected individuals of either sex. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK573670_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK573670_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/pot1-tpd/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/ppp2r1a-ndd/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK573670_"><span class="title" itemprop="name"><i>PPP1R12A</i>-Related Urogenital and/or Brain Malformation Syndrome</span></h1><p class="contrib-group"><span itemprop="author">Ebba Alkhunaizi</span>, MD and <span itemprop="author">David Chitayat</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK573670_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK573670_ai__"><div class="contrib half_rhythm"><span itemprop="author">Ebba Alkhunaizi</span>, MD<div class="affiliation small">Department of Clinical Genetics<br />North York General Hospital<br />Toronto, Ontario, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.lligcm.liam@izianuhkla.abbe" class="oemail">ac.lligcm.liam@izianuhkla.abbe</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">David Chitayat</span>, MD<div class="affiliation small">The Prenatal Diagnosis and Medical Genetics Program<br />Department of Obstetrics and Gynecology<br />Mount Sinai Hospital;<br />Division of Clinical and Metabolic Genetics<br />Department of Pediatrics<br />The Hospital for Sick Children<br />University of Toronto<br />Toronto, Ontario, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.htlaehianis@tayatihc.divad" class="oemail">ac.htlaehianis@tayatihc.divad</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 9, 2021</span>; Last Revision: <span itemprop="dateModified">March 7, 2024</span>.</p><p><em>Estimated reading time: 20 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="ppp1r12a-ubm.Summary" itemprop="description"><h2 id="_ppp1r12a-ubm_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Individuals with <i>PPP1R12A</i>-related urogenital and/or brain malformation syndrome (UBMS) usually present with multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies, most commonly involving the brain and/or urogenital systems. The brain abnormalities are variable, with the most severe belonging to the holoprosencephaly spectrum and associated with moderate-to-profound intellectual disability, seizures, and feeding difficulties. In individuals without brain involvement, variable degrees of developmental delay and/or intellectual disability may be present, although normal intelligence has been seen in a minority of affected individuals. Eye (strabismus, microphthalmia/anophthalmia) and skeletal abnormalities (kyphoscoliosis, joint contractures) can also be present in affected individuals of either sex. Regardless of the presence of a brain malformation, affected individuals with a 46,XY <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> complement may have a difference of sex development (DSD) with gonadal dysgenesis associated with ambiguous genitalia or phenotypic female genitalia.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>PPP1R12A</i>-related UBMS is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>PPP1R12A</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Gonadectomy should be considered in individuals with dysgenetic gonads; referral of 46,XY undervirilized individuals to a urologist or gynecologist for consideration of surgery to address hypospadias, bifid scrotum, urogenital sinus abnormalities, and cryptorchidism; referral to an endocrinologist for treatment for induction of puberty and postpubertal hormonal issues for those with gonadal abnormalities; referral to a psychologist or multidisciplinary DSD clinic, if available. Treatment of feeding difficulties including consideration of gastrostomy tube placement for those with persistent feeding issues or failure to thrive; standard treatment for renal anomalies, epilepsy, developmental delay/intellectual disability, constipation, bowel atresia, hearing impairment, vision abnormalities/strabismus, kyphoscoliosis, and joint contractures, as needed.</p><p><i>Surveillance:</i> Regular follow up by an interdisciplinary DSD team (if available) including endocrinology, genetics, gynecology, psychology, and urology for those who had DSD as part of their features. Measurement of growth parameters, evaluation of nutritional status and safety of oral intake, assessment for constipation, monitoring of developmental progress and educational needs, monitoring for changes in seizures, and assessment for new neurologic manifestations at each visit; monitoring for timing and progression of puberty at each visit starting in late childhood through adolescence; assessment for scoliosis or kyphosis at each visit until growth is complete; ophthalmology and audiology evaluations annually or as clinically indicated.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>PPP1R12A</i>-related UBMS is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. If the <i>PPP1R12A</i> pathogenic variant identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>. Once the <i>PPP1R12A</i> pathogenic variant has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="ppp1r12a-ubm.Diagnosis"><h2 id="_ppp1r12a-ubm_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for <i>PPP1R12A-</i>related urogenital and/or brain malformation syndrome (<i>PP1R12A</i>-related UBMS) have been published.</p><div id="ppp1r12a-ubm.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>PPP1R12A</i>-related UBMS <b>should be suspected</b> in individuals with the following clinical and imaging findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Atypical external genitalia in individuals with a 46,XY <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> complement, including:</div><ul><li class="half_rhythm"><div>Normal female external genitalia</div></li><li class="half_rhythm"><div>Urogenital sinus abnormalities</div></li><li class="half_rhythm"><div>Undervirilized male external genitalia with a high <a class="def" href="/books/n/gene/glossary/def-item/insertion/">insertion</a> of the scrotum, bifid scrotum with or without cryptorchidism, micropenis, hypospadias with or without chordee, and anterior positioning of the anus.</div></li></ul></li><li class="half_rhythm"><div>Microcephaly or macrocephaly with variable degrees of developmental delay, intellectual disability, and/or autistic features</div></li><li class="half_rhythm"><div>Brain malformations (See <b>Imaging findings</b>.)</div></li><li class="half_rhythm"><div>Eye abnormalities such as strabismus, microphthalmia/anophthalmia</div></li><li class="half_rhythm"><div>Skeletal anomalies (e.g., unilateral or bilateral fifth-finger clinodactyly, syndactyly of the toes, kyphoscoliosis)</div></li></ul><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div>Brain MRI imaging demonstrating:</div><ul><li class="half_rhythm"><div>Alobar, semilobar, or middle interhemispheric variant holoprosencephaly</div></li><li class="half_rhythm"><div>Abnormalities of the corpus callosum</div></li><li class="half_rhythm"><div>Anencephaly</div></li><li class="half_rhythm"><div>Cortical dysplasia (polymicrogyria, heterotopia)</div></li></ul></li><li class="half_rhythm"><div>Abdominal/pelvic ultrasound/MRI demonstrating:</div><ul><li class="half_rhythm"><div>Abnormal internal genitalia in 46,XY individuals, including müllerian duct remnants (uterine structure, cervix and/or upper part of the vagina)</div></li><li class="half_rhythm"><div>Structural renal abnormalities including duplicated renal collecting system</div></li></ul></li></ul></div><div id="ppp1r12a-ubm.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>PPP1R12A</i>-related UBMS <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>PPP1R12A</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK573670/table/ppp1r12a-ubm.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobppp1r12aubmTmoleculargenetictesting">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#ppp1r12a-ubm.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include any likely pathogenic variants. (2) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>PPP1R12A</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> and <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Individuals with the distinctive findings described in <a href="#ppp1r12a-ubm.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#ppp1r12a-ubm.Option_1">Option 1</a>), whereas those with a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> indistinguishable from many other inherited disorders with undervirilization in 46,XY individuals and/or brain malformations are more likely to be diagnosed using genomic testing (see <a href="#ppp1r12a-ubm.Option_2">Option 2</a>).</p><div id="ppp1r12a-ubm.Option_1"><h4>Option 1</h4><p>When the phenotypic and imaging findings suggest the diagnosis of <i>PPP1R12A</i>-related UBMS, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>PPP1R12A</i> is performed first to detect <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A differences of sex development or brain malformation <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>PPP1R12A</i> and other genes of interest (see <a href="#ppp1r12a-ubm.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="ppp1r12a-ubm.Option_2"><h4>Option 2</h4><p>When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other inherited disorders characterized by brain malformations and/or undervirilization in a 46,XY individual, comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing may be considered. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="ppp1r12a-ubm.T.molecular_genetic_testing" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>PPP1R12A</i>-Related Urogenital and/or Brain Malformation Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.molecular_genetic_testing/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.molecular_genetic_testing_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_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_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2, 3</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PPP1R12A</i>
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</td><td headers="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></td><td headers="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12/12 <sup>5</sup></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>6</sup></td><td headers="hd_h_ppp1r12a-ubm.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>7</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="ppp1r12a-ubm.TF.1.1"><p class="no_margin">See <a href="/books/NBK573670/#ppp1r12a-ubm.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="ppp1r12a-ubm.TF.1.2"><p class="no_margin">See <a href="#ppp1r12a-ubm.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="ppp1r12a-ubm.TF.1.3"><p class="no_margin">Fourteen additional individuals with contiguous <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions (not included in these calculations) have been reported in the literature [<a class="bk_pop" href="#ppp1r12a-ubm.REF.niclass.2020.2133">Niclass et al 2020</a>] or in the Decipher database (see <a href="#ppp1r12a-ubm.Genetically_Related_Allelic">Genetically Related Disorders</a>).</p></div></dd><dt>4. </dt><dd><div id="ppp1r12a-ubm.TF.1.4"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>5. </dt><dd><div id="ppp1r12a-ubm.TF.1.5"><p class="no_margin">
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<a class="bk_pop" href="#ppp1r12a-ubm.REF.hughes.2020.121">Hughes et al [2020]</a>
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</p></div></dd><dt>6. </dt><dd><div id="ppp1r12a-ubm.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>7. </dt><dd><div id="ppp1r12a-ubm.TF.1.7"><p class="no_margin">No data on detection rate of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> are available.</p></div></dd></dl></div></div></div></div></div></div><div id="ppp1r12a-ubm.Clinical_Characteristics"><h2 id="_ppp1r12a-ubm_Clinical_Characteristics_">Clinical Characteristics</h2><div id="ppp1r12a-ubm.Clinical_Description"><h3>Clinical Description</h3><p>Individuals with <i>PPP1R12A</i>-related UBMS present with multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies including brain abnormalities (holoprosencephaly spectrum and others) and urogenital malformations. To date, 12 individuals have been identified with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>PPP1R12A</i> [<a class="bk_pop" href="#ppp1r12a-ubm.REF.hughes.2020.121">Hughes et al 2020</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="ppp1r12a-ubm.T.ppp1r12arelated_urogenita" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>PPP1R12A</i>-Related Urogenital and/or Brain Malformation Syndrome: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.ppp1r12arelated_urogenita/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.ppp1r12arelated_urogenita_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons<br />w/Feature</th><th id="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_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_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">46,XY DSD & genitourinary anomalies</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9/12</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/12</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain malformations</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5/12</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically along the holoprosencephaly spectrum</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eye or vision problems</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3/12</td><td headers="hd_h_ppp1r12a-ubm.T.ppp1r12arelated_urogenita_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DSD = disorders/differences of sex development</p></div></dd></dl></div></div></div><p><b>46,XY differences of sex development (DSD) / genitourinary anomalies</b> are the primary manifestations in <i>PPP1R12A</i>-related UBMS.</p><ul><li class="half_rhythm"><div>Atypical external genitalia in individuals with a 46,XY <a class="def" href="/books/n/gene/glossary/def-item/karyotype/">karyotype</a> range from mild to severe undervirilization and can include:</div><ul><li class="half_rhythm"><div>Micropenis</div></li><li class="half_rhythm"><div>Chordee</div></li><li class="half_rhythm"><div>Variable degrees of hypospadias</div></li><li class="half_rhythm"><div>Bifid and high <a class="def" href="/books/n/gene/glossary/def-item/insertion/">insertion</a> of the scrotum</div></li><li class="half_rhythm"><div>Urogenital sinus abnormalities</div></li><li class="half_rhythm"><div>Normal appearing female external genitalia</div></li></ul></li><li class="half_rhythm"><div>Gonadal abnormalities can range from cryptorchidism to complete gonadal dysgenesis.</div><ul><li class="half_rhythm"><div>Gonads may be dysgenetic.</div></li><li class="half_rhythm"><div>In the most severe cases, streak gonads have been found.</div></li></ul></li><li class="half_rhythm"><div>Müllerian structures, including fallopian tubes, uterus, and upper part of the vagina, may be present.</div></li></ul><p><b>Neurologic.</b> Variable degrees of developmental delay and intellectual disability were reported in seven of 12 affected individuals. Neurodevelopmental abnormalities included attention-deficit/hyperactivity disorder (ADHD) and autistic features. Other neurologic features reported in single individuals include dystonia, appendicular hypotonia with foot pronation, unsteady gait, and seizure disorder. Normal intelligence has also been reported in some cases.</p><p><b>Brain imaging findings.</b> Two individuals with holoprosencephaly (semilobar and syntelencephaly/middle interhemispheric variant) and two with corpus callosum abnormalities have been reported. Other anomalies reported in single individuals include: encephalocele, colpocephaly, acrania/exencephaly, absent septum pellucidum, Chiari malformation, cortical dysplasia/polymicrogyria, leukomalacia, and gray matter heterotopia.</p><p><b>Feeding.</b> In individuals with a severe brain malformation, feeding may be difficult. Neonates with feeding difficulties can develop hyperbilirubinemia. Feeding often improves during the first few months of life, but typically worsens if seizures develop.</p><ul><li class="half_rhythm"><div>Poor feeding in newborns is usually managed by nasogastric tube feedings, as the feeding problems often improve during the first weeks of life (see Management, <a href="#ppp1r12a-ubm.Treatment_of_Manifestations">Treatment of Manifestations</a>).</div></li><li class="half_rhythm"><div>Feeding may worsen with intercurrent illnesses and with advancing age and size. In this scenario, gastrostomy tube placement may be considered.</div></li><li class="half_rhythm"><div>Individuals with low central tone frequently develop constipation.</div></li></ul><p><b>Eye findings.</b> Three of 12 affected individuals were reported with various eye abnormalities including strabismus, astigmatism, hyperopia, unilateral or alternating esotropia, rod and cone dysfunction, decreased vision, and latent nystagmus.</p><p><b>Limb/skeletal anomalies</b> have included fifth-finger clinodactyly, syndactyly of all toes, kyphoscoliosis, joint contractures (not otherwise specified), and ulnar deviation of the hand</p><p>
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<b>Manifestations reported in single individuals</b>
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</p><ul><li class="half_rhythm"><div>Growth abnormalities: microcephaly, macrocephaly, intrauterine growth restriction (IUGR), postnatal growth restriction/failure to thrive (FTT) and decreased subcutaneous fat</div></li><li class="half_rhythm"><div>Dysmorphic features including long face, facial asymmetry, arched eyebrows, widely-spaced eyes, hypotelorism/closely-spaced eyes, ptosis, long or short palpebral fissures, long eyelashes, epicanthal folds, short and upturned nose, micrognathia, large low-set and protruding ears, preauricular pit, earlobe creases, long philtrum</div></li><li class="half_rhythm"><div>Gastrointestinal: omphalocele; jejunal and ileal atresia with aberrant mesenteric blood supply</div></li><li class="half_rhythm"><div>Pyelectasis</div></li><li class="half_rhythm"><div>Patent ductus arteriosus</div></li></ul></div><div id="ppp1r12a-ubm.GenotypePhenotype_Correlati"><h3>Genotype-Phenotype Correlations</h3><p>No <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been identified.</p></div><div id="ppp1r12a-ubm.Prevalence"><h3>Prevalence</h3><p><i>PPP1R12A</i>-related UBMS is rare: 12 individuals have been reported to date [<a class="bk_pop" href="#ppp1r12a-ubm.REF.hughes.2020.121">Hughes et al 2020</a>]. The prevalence has not been determined.</p></div></div><div id="ppp1r12a-ubm.Genetically_Related_Allelic"><h2 id="_ppp1r12a-ubm_Genetically_Related_Allelic_">Genetically Related (Allelic) Disorders</h2><p><b>Deletion 12q21.</b> Fourteen individuals with a <a class="def" href="/books/n/gene/glossary/def-item/contiguous-gene-deletion/">contiguous gene deletion</a> involving <i>PPP1R12A</i> and surrounding genes in the 12q21 region have been reported in the literature [<a class="bk_pop" href="#ppp1r12a-ubm.REF.niclass.2020.2133">Niclass et al 2020</a>] or in the <a href="https://www.deciphergenomics.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Decipher</a> database. Variable features were reported in individuals with partial or complete deletion of the whole gene include <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> facial features, developmental delay, hydrocephalus or ventriculomegaly, growth restriction, ectodermal anomalies, spastic diplegia or axial hypotonia, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart defects, and renal malformations. No individuals with 46,XY DSD were identified in this group of individuals [<a class="bk_pop" href="#ppp1r12a-ubm.REF.niclass.2020.2133">Niclass et al 2020</a>].</p><p><b>Sporadic tumors.</b> Somatic copy number variants in <i>PPP1R12A</i> or fusion proteins with <i>PPP1R12A</i> at the 12q21.1 to 12q21.31 <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> that are not present in the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> [<a class="bk_pop" href="#ppp1r12a-ubm.REF.zhang.2015.417184">Zhang et al 2015</a>, <a class="bk_pop" href="#ppp1r12a-ubm.REF.gupta.2019.48">Gupta et al 2019</a>] have been reported in colorectal cancer and alveolar and sarcomatoid rhabdomyosarcoma. In these circumstances predisposition to these tumors is not heritable. For more information, see <a href="#ppp1r12a-ubm.Cancer_and_Benign_Tumors">Cancer and Benign Tumors</a>.</p></div><div id="ppp1r12a-ubm.Differential_Diagnosis"><h2 id="_ppp1r12a-ubm_Differential_Diagnosis_">Differential Diagnosis</h2><div id="ppp1r12a-ubm.T.genes_of_interest_in_the" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of <i>PPP1R12A</i>-Related Urogenital and/or Brain Malformation Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.genes_of_interest_in_the/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.genes_of_interest_in_the_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of DiffDx Disorder</th></tr><tr><th headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4" id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<i>PPP1R12A</i>-related UBMS</th><th headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4" id="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from <i>PPP1R12A</i>-related UBMS</th></tr></thead><tbody><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Conditions w/genitourinary abnormalities</b>
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</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AR</i>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/androgen/">Androgen insensitivity syndrome</a>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GU abnormalities & sex reversal</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lack of multiple malformation & DD/ID</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATRX</i>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/xlmr/">Alpha-thalassemia X-linked intellectual disability syndrome</a>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GU malformation incl abnormal genitalia & sex reversal</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinctive craniofacial features; mild anemia secondary to alpha-thalassemia</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>WT1</i>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Denys-Drash syndrome (See <a href="/books/n/gene/wt1-dis/"><i>WT1</i> Disorder</a>.)</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GU malformation incl ambiguous genitalia & müllerian structures on ultrasound</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diffuse mesangial sclerosis on renal biopsy; Wilms tumor; lack of DD/ID</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CDKN1C</i>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/image/">IMAGe syndrome</a>
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</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">IUGR; GU abnormalities (males)</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adrenal hypoplasia congenita; metaphyseal dysplasia</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Conditions w/genitourinary abnormalities & brain malformations</b>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DHCR7</i>
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||
</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/slo/">Smith-Lemli-Opitz syndrome</a>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypospadias; ambiguous genitalia; 2-3 toe syndactyly; microcephaly; holoprosencephaly; IUGR/short stature</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Characteristic facial features (narrow forehead, epicanthal folds, ptosis, short mandible w/preservation of jaw width, short nose, anteverted nares, & low-set ears); postaxial polydactyly; cleft palate</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ARX</i>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> lissencephaly w/ambiguous genitalia (OMIM <a href="https://omim.org/entry/300215" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300215</a>)</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GU malformation incl ambiguous genitalia; brain malformations incl cortical malformation & corpus callosum abnormalities</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Perinatal encephalopathy w/intractable seizures; lissencephaly a predominant finding; chronic diarrhea; high male lethality in 1st 3 mos of life</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>RAB18</i>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Warburg micro syndrome (OMIM <a href="https://omim.org/entry/614222" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614222</a>)</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GU malformation incl hypogonadism; microcephaly; corpus callosum abnormalities</td><td headers="hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_1_4 hd_h_ppp1r12a-ubm.T.genes_of_interest_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic abnormalities incl <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cataracts, atonic pupils, optic nerve atrophy, microphthalmia, microcornea</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; DD = developmental delay; DiffDx = differential diagnosis; GU = genitourinary; ID = intellectual disability; IUGR = intrauterine growth restriction; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd></dl></div></div></div><p>Other disorders to consider in the differential diagnosis of <i>PPP1R12A</i>-related UBMS include the following (shared clinical findings indicated in parentheses):</p><ul><li class="half_rhythm"><div>Trisomy 13 (holoprosencephaly, GU malformation)</div></li><li class="half_rhythm"><div>Pseudotrisomy 13 syndrome (OMIM <a href="https://omim.org/entry/264480" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">264480</a>) (holoprosencephaly)</div></li></ul></div><div id="ppp1r12a-ubm.Management"><h2 id="_ppp1r12a-ubm_Management_">Management</h2><p>No clinical practice guidelines for <i>PPP1R12A</i>-related UBMS have been published.</p><div id="ppp1r12a-ubm.Evaluations_Following_Initi"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>PPP1R12A</i>-related UBMS, the evaluations summarized in <a href="/books/NBK573670/table/ppp1r12a-ubm.T.recommended_evaluations_f/?report=objectonly" target="object" rid-ob="figobppp1r12aubmTrecommendedevaluationsf">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="ppp1r12a-ubm.T.recommended_evaluations_f" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>PPP1R12A</i>-Related Urogenital and/or Brain Malformations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.recommended_evaluations_f/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.recommended_evaluations_f_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_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_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genitourinary</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of external genitalia for anomalies, incl:
|
||
<ul><li class="half_rhythm"><div>Attempt to palpate gonads in the scrotum/labioscrotal folds</div></li><li class="half_rhythm"><div>Inspection of scrotum / labioscrotal folds, phallic structure for length, breadth, chordee, foreskin, & location of urethral opening, labio/scrotal-anal distance</div></li><li class="half_rhythm"><div>Presence of vaginal dimple/introitus</div></li><li class="half_rhythm"><div>Assessment of labioscrotal folds for fusion, rugation, & pigmentation</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to a multidisciplinary DSD team incl urology, endocrinology, genetics, gynecology, & psychology, if possible.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider <a class="def" href="/books/n/gene/glossary/def-item/karyotype/">karyotype</a> w/<a class="def" href="/books/n/gene/glossary/def-item/fish/">FISH</a> for <i>SRY</i> or <a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a>.</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In those w/external genital anomalies & in phenotypic females</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Renal/abdominal/pelvic ultrasound</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for renal anomalies & müllerian structures</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrinology</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider obtaining hormone studies <sup>1</sup> between age 2 wks & 3 mos & at pubertal age to assess gonadal function.</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to endocrinologist in those w/46,XY DSD.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurology</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurology eval</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl brain MRI</div></li><li class="half_rhythm"><div>Consider EEG if seizures are a concern.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech-language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constitutional</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of growth parameters</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl weight, length/height, & head circumference</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>GI/Feeding</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology/nutrition/feeding team eval in those w/feeding issues &/or FTT</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of nutritional status & aspiration risk</div></li><li class="half_rhythm"><div>Consider eval for nasogastric or gastrostomy tube placement in those w/severe feeding issues, dysphagia, &/or aspiration risk.</div></li><li class="half_rhythm"><div>Consider eval for structural GI issues, if signs/symptoms are consistent w/obstruction.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmology</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for strabismus, cone/rod dysfunction, & refractive error</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Audiology <sup>2</sup></b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for hearing loss in those w/speech delay &/or a known brain malformation</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for digital & joint anomalies.</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral for orthopedics assessment / hand surgery if needed.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>3</sup></td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_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>PPP1R12A</i>-related UBMS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#ppp1r12a-ubm.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_evaluations_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DSD = differences of sex development; <a class="def" href="/books/n/gene/glossary/def-item/fish/">FISH</a> = fluorescence in situ hybridization; FTT = failure to thrive; GI = gastrointestinal; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="ppp1r12a-ubm.TF.4.1"><p class="no_margin">Including but not limited to total testosterone, dihydrotestosterone, inhibin B, anti-müllerian hormone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) to assess for gonadal function</p></div></dd><dt>2. </dt><dd><div id="ppp1r12a-ubm.TF.4.2"><p class="no_margin">Although hearing loss is not a primary feature of <i>PPP1R12A</i>-related UBMS, assessment of hearing in an individual with significant developmental delay and/or brain malformation is recommended.</p></div></dd><dt>3. </dt><dd><div id="ppp1r12a-ubm.TF.4.3"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="ppp1r12a-ubm.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="ppp1r12a-ubm.T.treatment_of_manifestatio" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>PPP1R12A</i>-Related Urogenital and/or Brain Malformations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.treatment_of_manifestatio/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.treatment_of_manifestatio_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_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_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>46,XY DSD</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consider gonadectomay in those w/dysgenetic gonads.</div></li><li class="half_rhythm"><div>In 46,XY undervirilized persons, referral to urologist or gynecologist for standard treatment of atypical genitalia/hypospadias, cryptorchidism, &/or urogenital sinus anomalies</div></li><li class="half_rhythm"><div>Standard treatment of hormonal issues at & after puberty, incl sex HRT</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consider referral to endocrinologist for hormonal issues.</div></li><li class="half_rhythm"><div>Consider referral to psychologist or a multidisciplinary DSD clinic, if available.</div></li><li class="half_rhythm"><div>For further details on 46,XY DSD mgmt see <a href="/books/n/gene/gonad-dys-46xy/">Nonsyndromic Disorders of Testicular Development.</a></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal anomalies</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per nephrologist &/or urologist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Epilepsy</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment w/ASM by experienced neurologist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DD/ID</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#ppp1r12a-ubm.Developmental_Delay__Intell">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Poor weight</b>
|
||
<br />
|
||
<b>gain/FTT/</b>
|
||
<br />
|
||
<b>GERD/</b>
|
||
<br />
|
||
<b>Aspiration</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Feeding therapy</div></li><li class="half_rhythm"><div>Gastrostomy tube placement may be required for persistent feeding issues or FTT.</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia, incl episodes of aspiration pneumonia</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constipation</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Stool softeners, prokinetics, osmotic agents, or laxatives as needed</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Bowel atresia</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per surgeon & gastroenterologist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
<br />
|
||
<b>impairment</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard therapy per audiologist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Abnormal</b>
|
||
<br />
|
||
<b>vision &/or</b>
|
||
<br />
|
||
<b>strabismus</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by ophthalmologist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community vision services through early intervention or school district</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Kyphoscoliosis/</b>
|
||
<br />
|
||
<b>Joint contractures</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per orthopedist</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/</b>
|
||
<br />
|
||
<b>Community</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications & supplies.</div></li><li class="half_rhythm"><div>Ensure psychological support for those w/gender identity concerns.</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.treatment_of_manifestatio_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or <a href="https://www.specialolympics.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Special Olympics</a>.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DSD = differences of sex development; ASM = anti-seizure medication; DD = developmental delay; FTT = failure to thrive; GERD = gastroesophageal reflux disease; HRT = hormone replacement therapy; ID = intellectual disability; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="ppp1r12a-ubm.TF.5.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div><div id="ppp1r12a-ubm.Developmental_Delay__Intell"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="ppp1r12a-ubm.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li><li class="half_rhythm"><div>For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox<sup>®</sup>, anti-parkinsonian medications, or orthopedic procedures.</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction</b> should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.</p></div><div id="ppp1r12a-ubm.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat ADHD, when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="ppp1r12a-ubm.Surveillance"><h3>Surveillance</h3><div id="ppp1r12a-ubm.T.recommended_surveillance" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>PPP1R12A</i>-Related Urogenital and/or Brain Malformations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.T.recommended_surveillance/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.T.recommended_surveillance_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_ppp1r12a-ubm.T.recommended_surveillance_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_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measurement of growth parameters</div></li><li class="half_rhythm"><div>Eval of nutritional status & safety of oral intake</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_3" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for constipation & feeding difficulties.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor those w/seizures as clinically indicated.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assess for new manifestations such as seizures, changes in tone, movement disorders.</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>DSD <sup>1</sup></b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor timing & progression of puberty & need for puberty induction & hormone replacement therapy.</div></li><li class="half_rhythm"><div>Assess for gender identity concerns.</div></li></ul>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit starting in late childhood & through adolescence</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor skeletal complications such as scoliosis or kyphosis.</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit until growth is completed</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology eval</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as clinically indicated</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td></tr><tr><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Miscellaneous/</b>
|
||
<br />
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td><td headers="hd_h_ppp1r12a-ubm.T.recommended_surveillance_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">DSD = disorder/differences of sex development</p></div></dd><dt>1. </dt><dd><div id="ppp1r12a-ubm.TF.6.1"><p class="no_margin">Routine follow up by an interdisciplinary DSD team (if available) including endocrinology, genetics, obstetrics/gynecology, psychology, and urology.</p></div></dd></dl></div></div></div></div><div id="ppp1r12a-ubm.Evaluation_of_Relatives_at"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#ppp1r12a-ubm.Genetic_Counseling">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="ppp1r12a-ubm.Therapies_Under_Investigati"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="ppp1r12a-ubm.Genetic_Counseling"><h2 id="_ppp1r12a-ubm_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="ppp1r12a-ubm.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>PPP1R12A</i>-related urogenital and/or brain malformation syndrome (<i>PPP1R12A</i>-related UBMS) is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="ppp1r12a-ubm.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>All probands reported to date with <i>PPP1R12A</i>-related UBMS whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm their genetic status and to allow reliable counseling regarding <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> and <a class="def" href="/books/n/gene/glossary/def-item/prenatal-diagnosis/">prenatal diagnosis</a> options.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bk_pop" href="#ppp1r12a-ubm.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from a parent with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (or somatic and germline) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. (To date, parental mosaicism has not been reported in <i>PPP1R12A</i>-related UBMS.) Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> and will not detect a pathogenic variant that is present in the germ cells only.</div></li></ul></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is known to have the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs for inheriting the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>If the <i>PPP1R12A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#ppp1r12a-ubm.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with <i>PPP1R12A</i>-related UBMS has a 50% chance of inheriting the <i>PPP1R12A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p><p><b>Other family members.</b> Given that all probands with <i>PPP1R12A</i>-related UBMS reported to date have the disorder as a result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the risk to other family members is presumed to be low.</p></div><div id="ppp1r12a-ubm.Related_Genetic_Counseling"><h3>Related Genetic Counseling Issues</h3><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to parents of affected individuals.</div></li></ul></div><div id="ppp1r12a-ubm.Prenatal_Testing_and_Preimp"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Risk to future pregnancies is presumed to be low as the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> most likely has a <i>de novo PPP1R12A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. There is, however, a <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> (~1%) to sibs based on the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#ppp1r12a-ubm.REF.rahbari.2016.126">Rahbari et al 2016</a>]. Given this risk, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> may be considered.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="ppp1r12a-ubm.Resources"><h2 id="_ppp1r12a-ubm_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>National Human Genome Research Institute (NHGRI)</b>
|
||
</div><div>
|
||
<a href="https://www.genome.gov/Genetic-Disorders/Holoprosencephaly" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Learning About Holoprosencephaly</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Accord Alliance</b>
|
||
</div><div><b>Phone:</b> 602-492-4144</div><div>
|
||
<a href="http://www.AccordAlliance.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.AccordAlliance.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Families for Hope</b>
|
||
</div><div>1219 North Wittfield Street</div><div>Indianapolis IN 46229</div><div><b>Phone:</b> 888-533-4443</div><div><b>Email:</b> Info@FamiliesforHoPE.org</div><div>
|
||
<a href="https://familiesforhope.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.familiesforhope.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Genetic and Rare Diseases Information Center (GARD)</b>
|
||
</div><div>
|
||
<a href="https://rarediseases.info.nih.gov/diseases/6665/holoprosencephaly/cases/27877" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Holoprosencephaly</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>INCIID</b>
|
||
</div><div>InterNational Council on Infertility Information Dissemination</div><div><b>Email:</b> INCIIDinfo@inciid.org</div><div>
|
||
<a href="http://www.inciid.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">inciid.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
|
||
</div><div>PO Box 5801</div><div>Bethesda MD 20824</div><div><b>Phone:</b> 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)</div><div>
|
||
<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Holoprosencephaly-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Holoprosencephaly Information Page</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Organization for Rare Disorders (NORD)</b>
|
||
</div><div>
|
||
<a href="https://rarediseases.org/rare-diseases/holoprosencephaly/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Holoprosencephaly</a>
|
||
</div></li></ul>
|
||
</div><div id="ppp1r12a-ubm.Molecular_Genetics"><h2 id="_ppp1r12a-ubm_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="ppp1r12a-ubm.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK573670/table/ppp1r12a-ubm.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/4659" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>PPP1R12A</i>
|
||
</a>
|
||
</td><td headers="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=4659" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12q21<wbr style="display:inline-block"></wbr>.2-q21.31</a>
|
||
</td><td headers="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/O14974" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein phosphatase 1 regulatory subunit 12A</a>
|
||
</td><td headers="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PPP1R12A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PPP1R12A</a>
|
||
</td><td headers="hd_b_ppp1r12a-ubm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=PPP1R12A[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PPP1R12A</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="ppp1r12a-ubm.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="ppp1r12a-ubm.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for PPP1R12A-Related Urogenital and/or Brain Malformation Syndrome (<a href="/omim/602021,618820" 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/NBK573670/table/ppp1r12a-ubm.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ppp1r12a-ubm.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/602021" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">602021</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 12A; PPP1R12A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/618820" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">618820</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME; GUBS</td></tr></tbody></table></div></div><div id="ppp1r12a-ubm.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>PPP1R12A</i> encodes a component of myosin phosphatase (MP), a key enzyme instrumental in the regulation of cell morphology and motility [<a class="bk_pop" href="#ppp1r12a-ubm.REF.grassie.2011.147">Grassie et al 2011</a>, <a class="bk_pop" href="#ppp1r12a-ubm.REF.kiss.2019.2">Kiss et al 2019</a>]. MP activates when PP1c is unphosphorylated and bound. Phosphorylation of specific consensus sites on PPP1R12A by protein kinases leads to inhibition of its activity [<a class="bk_pop" href="#ppp1r12a-ubm.REF.ito.2004.197">Ito et al 2004</a>]. Pathogenic variants in <i>PPP1R12A</i> prevent PPP1R12A from binding to PP1c and result in a nonfunctional MP [<a class="bk_pop" href="#ppp1r12a-ubm.REF.huang.2008.3209">Huang et al 2008</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p></div><div id="ppp1r12a-ubm.Cancer_and_Benign_Tumors"><h3>Cancer and Benign Tumors</h3><p>The number of copies of <i>PPP1R12A</i> was correlated with the prediction of recurrence and survival in individuals with Stage III colorectal cancer treated with oxaliplatin-based chemotherapy [<a class="bk_pop" href="#ppp1r12a-ubm.REF.zhang.2015.417184">Zhang et al 2015</a>]. Moreover, both a pure alveolar and sarcomatoid rhabdomyosarcoma of the urinary bladder demonstrated a novel fusion involving <i>PPP1R12A</i> fusions at the 12q21.1 to 12q21.31 <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a>; the exact role of this fusion has not been defined [<a class="bk_pop" href="#ppp1r12a-ubm.REF.gupta.2019.48">Gupta et al 2019</a>].</p></div></div><div id="ppp1r12a-ubm.Chapter_Notes"><h2 id="_ppp1r12a-ubm_Chapter_Notes_">Chapter Notes</h2><div id="ppp1r12a-ubm.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>7 March 2024 (ea) Revision: removed information regarding individuals with a 46,XX <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> complement</div></li><li class="half_rhythm"><div>9 September 2021 (ma) Review posted live</div></li><li class="half_rhythm"><div>8 January 2021 (ea) Original submission</div></li></ul></div></div><div id="ppp1r12a-ubm.References"><h2 id="_ppp1r12a-ubm_References_">References</h2><div id="ppp1r12a-ubm.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.grassie.2011.147">Grassie
|
||
ME, Moffat
|
||
LD, Walsh
|
||
MP, MacDonald
|
||
JA. The myosin phosphatase targeting protein (MYPT) family: A regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1δ.
|
||
Arch Biochem Biophys.
|
||
2011;510:147–59.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/21291858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21291858</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.gupta.2019.48">Gupta
|
||
S, Sosa
|
||
CP, Kosari
|
||
F, Folpe
|
||
A, Bhinge
|
||
KN, Yang
|
||
L, Agahi
|
||
A, Johnson
|
||
SH, Frank
|
||
I, Boorjian
|
||
SA, Hansel
|
||
DE, Al-Ahmadie
|
||
HA, Reuter
|
||
VE, Vasmatzis
|
||
G, Jimenez
|
||
RE, Herrera-Hernandez
|
||
L, Cheville
|
||
JC. A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.
|
||
Hum Pathol.
|
||
2019;88:48–59.
|
||
[<a href="/pmc/articles/PMC8078053/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8078053</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30946934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30946934</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.huang.2008.3209">Huang
|
||
H, Ruan
|
||
H, Aw
|
||
MY, Hussain
|
||
A, Guo
|
||
L, Gao
|
||
C, Qian
|
||
F, Leung
|
||
T, Song
|
||
H, Kimelman
|
||
D, Wen
|
||
Z, Peng
|
||
J. Mypt1-mediated spatial positioning of Bmp2-producing cells is essential for liver organogenesis.
|
||
Development.
|
||
2008;135:3209–18.
|
||
[<a href="/pmc/articles/PMC5574253/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5574253</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18776143" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18776143</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.hughes.2020.121">Hughes
|
||
JJ, Alkhunaizi
|
||
E, Kruszka
|
||
P, Pyle
|
||
LC, Grange
|
||
DK, Berger
|
||
SI, Payne
|
||
KK, Masser-Frye
|
||
D, Hu
|
||
T, Christie
|
||
MR, Clegg
|
||
NJ, Everson
|
||
JL, Martinez
|
||
AF, Walsh
|
||
LE, Bedoukian
|
||
E, Jones
|
||
MC, Harris
|
||
CJ, Riedhammer
|
||
KM, Choukair
|
||
D, Fechner
|
||
PY, Rutter
|
||
MM, Hufnagel
|
||
SB, Roifman
|
||
M, Kletter
|
||
GB, Delot
|
||
E, Vilain
|
||
E, Lipinski
|
||
RJ, Vezina
|
||
CM, Muenke
|
||
M, Chitayat
|
||
D. Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital malformations.
|
||
Am J Hum Genet.
|
||
2020;106:121–8.
|
||
[<a href="/pmc/articles/PMC7042489/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7042489</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31883643" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31883643</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.ito.2004.197">Ito
|
||
M, Nakano
|
||
T, Erdödi
|
||
F, Hartshorne
|
||
DJ. Myosin phosphatase: Structure, regulation and function.
|
||
Mol Cell Biochem.
|
||
2004;259:197–209.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15124925" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15124925</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.kiss.2019.2">Kiss
|
||
A, Erdődi
|
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Myosin phosphatase: Unexpected functions of a long-known enzyme.
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Biochim Biophys Acta Mol Cell Res.
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2019;1866:2–15.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/30076859" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30076859</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.niclass.2020.2133">Niclass
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Joubert Madeleine, Pizzuti A, Grazia Giuffrida M, Bernardini L, Gilbert-Dussardier B, Bilan F, Egloff M. 12q21 deletion syndrome: narrowing the critical region down to 1.6 MB including SYT1 and PPP1R12A.
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Am J Med Genet A.
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2020;182:2133–8.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/32633079" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32633079</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.rahbari.2016.126">Rahbari
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[<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="ppp1r12a-ubm.REF.richards.2015.405">Richards
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PPP1R12A copy number is associated with clinical outcomes of stage III CRC receiving oxaliplatin-based chemotherapy.
|
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[<a href="/pmc/articles/PMC4465766/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4465766</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26113782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26113782</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> SATB2-Associated Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Zarate YA, Bosanko K, Fish J. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/28406602" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Myhre Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop 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