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<meta name="keywords" content="C0266667, arhinencephaly, congenital abnormality, cyclocephaly, cyclopia, cyclopia defect, cyclopia sequence, cyclopian defect, cyclops, cyclops eye, demyer sequence, holoprosencephaly 1, holoprosencephaly 1, isolated cases, holoprosencephaly type 1, holoprosencephaly, familial alobar, hpe1, isolated arhinencephaly, monophthalmus, single central eye, synophthalmia, synophthalmus, autosomal dominant, autosomal recessive, birth defects, chromosomal disease, chromosome, clinical features, clinical findings, clinical genetics, clinical recommendations, clinvar, congenital chromosomal disease, consumer genetic resources, cytogenetic location, disease characteristics, disease definitions, disease descriptions, disease ontology, disease synonyms, disease vocabulary, dysmorphology, entrez, familial disease, gene, gene-disease relationship, genereviews, genetic disease, genetic disorder, genetic terminology, genetic testing registry, genetics home reference, genomic disease, gtr, hereditary disease, heritable disease, hpo, human phenotype ontology, inherited disease, management guidelines, maternal inheritance, medgen, medical genetics, medical subject headings, mesh, mitochondrial inheritance, mode of inheritance, national center for biotechnology information, national institutes of health, national library of medicine, ncbi, nih, nlm, omim, ordo, orphanet, paternal inheritance, phenome, position statements, professional practice guidelines, rare disease, reference sequence, refseq, snomed ct, syndrome, undiagnosed diseases, x-linked recessive" /><meta name="description" content="Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context.&#13; Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity.&#13; See also schizencephaly (269160), which may be part of the phenotypic spectrum of HPE.&#13; Genetic Heterogeneity of Holoprosencephaly&#13; Several loci for holoprosencephaly have been mapped to specific chromosomal sites and the molecular defects in some cases of HPE have been identified. Holoprosencephaly-1 (HPE1) maps to chromosome 21q22. See also HPE2 (157170), caused by mutation in the SIX3 gene (603714) on 2p21; HPE3 (142945), caused by mutation in the SHH gene (600725) on 7q36; HPE4 (142946), caused by mutation in the TGIF gene (602630) on 18p11; HPE5 (609637), caused by mutation in the ZIC2 gene (603073) on 13q32; HPE6 (605934), mapped to 2q37; HPE7 (610828), caused by mutation in the PTCH1 gene (601309) on 9q22; HPE8 (609408), mapped to 14q13; HPE9 (610829), caused by mutation in the GLI2 gene (165230) on 2q14; HPE10 (612530), mapped to 1q41-q42; HPE11 (614226), caused by mutation in the CDON gene (608707) on 11q24; HPE12 (618500), caused by mutation in the CNOT1 gene (604917) on 16q21; HPE13 (301043), caused by mutation in the STAG2 gene (300826) on Xq25; and HPE14 (619895), caused by mutation in the PLCH1 gene (612835) on 3q25.&#13; Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE.&#13; Mutations in genes involved in the multiprotein cohesin complex, including STAG2, have been shown to be involved in midline brain defects such as HPE. Mutations in some of those genes cause Cornelia de Lange syndrome (CDLS; see 122470), and some patients with severe forms of CDLS may have midline brain defects. See, for example, CDLS2 (300590), CDLS3 (610759), and CDLS4 (614701)." /><meta name="robots" content="index,nofollow,noarchive" />
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<!--
UID=78617
ConceptID=C0266667
-->
<!--imgCountBooks = 6--><div class="ncbi_carousel" data-ncbicarousel-config="imageWidth:'100px',numItemsVisible:2,toggler:false"><div class="nc_header"><span class="img_strip_title">Images (6)</span></div><div class="nc_content"><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image006.gif" src-large="/books/NBK1530/bin/hpe-overview-Image006.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F6/" title="GeneReviews" target="_blank">details</a></div><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image001.gif" src-large="/books/NBK1530/bin/hpe-overview-Image001.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F1/" title="GeneReviews" target="_blank">details</a></div><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image004.gif" src-large="/books/NBK1530/bin/hpe-overview-Image004.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F4/" title="GeneReviews" target="_blank">details</a></div><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image002.gif" src-large="/books/NBK1530/bin/hpe-overview-Image002.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F2/" title="GeneReviews" target="_blank">details</a></div><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image005.gif" src-large="/books/NBK1530/bin/hpe-overview-Image005.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F5/" title="GeneReviews" target="_blank">details</a></div><div class="nc_item"><a class="figpopup"><img alt="Image from GeneReviews" src="/books/NBK1530/bin/hpe-overview-Image003.gif" src-large="/books/NBK1530/bin/hpe-overview-Image003.jpg" /></a><br /><a href="/books/NBK1530/figure/hpe-overview.F3/" title="GeneReviews" target="_blank">details</a></div></div></div><h1 class="medgenTitle"><div class="MedGenTitleText">Holoprosencephaly 1<span class="h1sub">(HPE1)</span></div></h1><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>78617</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information."><span class="highlight" style="background-color:">C0266667</span></a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div><table class="medgenTable"><tbody><tr><td>Synonyms:</td>
<td>Cyclopia; DEMYER SEQUENCE</td></tr>
<tr><td><span class="bold">SNOMED CT: </span></td>
<td>Cyclocephaly (205798005); Cyclopia (205798005); Monophthalmus (205798005); Synophthalmus (205798005); Synophthalmia (205798005); Cyclops (205798005)</td></tr>
<tr><td colspan="2" class="small"> </td></tr><tr><td>HPO:</td>
<td><a target="_blank" title="Human Phenotype Ontology" href="https://hpo.jax.org/app/browse/term/HP:0009914">HP:0009914</a></td></tr>
<tr><td>Monarch Initiative:</td>
<td><a href="https://monarchinitiative.org/disease/MONDO:0009349" target="_blank">MONDO:0009349</a></td></tr>
<tr><td>OMIM<span class="superscript">®</span>:</td>
<td><a href="https://omim.org/entry/236100" target="_blank">236100</a></td></tr>
<tr><td>Orphanet:</td>
<td><a target="_blank" title="Orphanet: The portal for rare diseases and orphan drugs" href="http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&amp;Expert=268936">ORPHA268936</a></td></tr></tbody></table></div><div class="rprt-body jig-ncbiinpagenav" data-jigconfig="smoothScroll: false, gotoTopLink: true, gotoTopLinkText: '', gotoTopLinkAttrs: {'title': 'Go to the top of the page'},allHeadingLevels: ['h1'], topOfPageTOC: true, tocId: 'my-toc'"><div id="rprt-tabs-1" class="rprt-tab"><div id="tb-termsProp-1"><div class="leftCol mgCol"><div>
<div class="portlet mgSection" id="ID_100">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Definition">Definition</h1><a sid="100" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln">Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context.&#13; Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity.&#13; See also schizencephaly (269160), which may be part of the phenotypic spectrum of HPE.&#13; Genetic Heterogeneity of Holoprosencephaly&#13; Several loci for holoprosencephaly have been mapped to specific chromosomal sites and the molecular defects in some cases of HPE have been identified. Holoprosencephaly-1 (HPE1) maps to chromosome 21q22. See also HPE2 (157170), caused by mutation in the SIX3 gene (603714) on 2p21; HPE3 (142945), caused by mutation in the SHH gene (600725) on 7q36; HPE4 (142946), caused by mutation in the TGIF gene (602630) on 18p11; HPE5 (609637), caused by mutation in the ZIC2 gene (603073) on 13q32; HPE6 (605934), mapped to 2q37; HPE7 (610828), caused by mutation in the PTCH1 gene (601309) on 9q22; HPE8 (609408), mapped to 14q13; HPE9 (610829), caused by mutation in the GLI2 gene (165230) on 2q14; HPE10 (612530), mapped to 1q41-q42; HPE11 (614226), caused by mutation in the CDON gene (608707) on 11q24; HPE12 (618500), caused by mutation in the CNOT1 gene (604917) on 16q21; HPE13 (301043), caused by mutation in the STAG2 gene (300826) on Xq25; and HPE14 (619895), caused by mutation in the PLCH1 gene (612835) on 3q25.&#13; Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE.&#13; Mutations in genes involved in the multiprotein cohesin complex, including STAG2, have been shown to be involved in midline brain defects such as HPE. Mutations in some of those genes cause Cornelia de Lange syndrome (CDLS; see 122470), and some patients with severe forms of CDLS may have midline brain defects. See, for example, CDLS2 (300590), CDLS3 (610759), and CDLS4 (614701). [from <a title="Online Mendelian Inheritance in Man" href="http://www.omim.org" class="defSource" target="_blank">OMIM</a>]</div>
</div>
<div class="portlet mgSection" id="ID_102">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Clinical_features">Clinical features</h1><a sid="102" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln clinfeat"><strong>From HPO</strong><br />
<div class="divPopper rprt" id="clin_1633603"><div><strong>Micropenis</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1633603</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C4551492</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/1633603">Feature record</a> | <a href="/medgen?term=%22Micropenis%22%5BClinical%20Features%5D%20OR%201633603%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_56289"><div><strong>Single ventricle</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>56289</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0152424</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">The presence of only one working lower chamber in the heart, usually with a virtual absence of the ventricular septum and usually present in conjunction with double inlet left or right ventricle.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/56289">Feature record</a> | <a href="/medgen?term=%22Single%20ventricle%22%5BClinical%20Features%5D%20OR%2056289%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_87607"><div><strong>Short stature</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>87607</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0349588</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Finding</dd></dl></div></div></div>
<div class="spaceAbove">A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/87607">Feature record</a> | <a href="/medgen?term=%22Short%20stature%22%5BClinical%20Features%5D%20OR%2087607%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_20693"><div><strong>Seizure</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>20693</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0036572</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Sign or Symptom</dd></dl></div></div></div>
<div class="spaceAbove">A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/20693">Feature record</a> | <a href="/medgen?term=%22Seizure%22%5BClinical%20Features%5D%20OR%2020693%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_104498"><div><strong>Corpus callosum, agenesis of</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>104498</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0175754</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600).&#13; Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/104498">Feature record</a> | <a href="/medgen?term=%22Corpus%20callosum%2C%20agenesis%20of%22%5BClinical%20Features%5D%20OR%20104498%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_120578"><div><strong>Cerebellar hypoplasia</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>120578</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0266470</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/120578">Feature record</a> | <a href="/medgen?term=%22Cerebellar%20hypoplasia%22%5BClinical%20Features%5D%20OR%20120578%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_452352"><div><strong>Ethmocephaly</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>452352</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0266680</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Ethmocephaly is the rarest form of holoprosencephaly, which occurs due to an incomplete cleavage of the forebrain. Clinically, the disease presents with a proboscis, hypotelorism, microphthalmos and malformed ears.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/452352">Feature record</a> | <a href="/medgen?term=%22Ethmocephaly%22%5BClinical%20Features%5D%20OR%20452352%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_140909"><div><strong>Alobar holoprosencephaly</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>140909</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0431363</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">A type of holoprosencephaly characterized by the presence of a single ventricle and no separation of the cerebral hemisphere. The single midline ventricle is often greatly enlarged.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/140909">Feature record</a> | <a href="/medgen?term=%22Alobar%20holoprosencephaly%22%5BClinical%20Features%5D%20OR%20140909%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_107838"><div><strong>Global developmental delay</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>107838</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0557874</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Finding</dd></dl></div></div></div>
<div class="spaceAbove">A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/107838">Feature record</a> | <a href="/medgen?term=%22Global%20developmental%20delay%22%5BClinical%20Features%5D%20OR%20107838%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_811461"><div><strong>Intellectual disability</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>811461</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C3714756</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Mental or Behavioral Dysfunction</dd></dl></div></div></div>
<div class="spaceAbove">Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/811461">Feature record</a> | <a href="/medgen?term=%22Intellectual%20disability%22%5BClinical%20Features%5D%20OR%20811461%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_346841"><div><strong>Generalized hypotonia</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>346841</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1858120</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Finding</dd></dl></div></div></div>
<div class="spaceAbove">Generalized muscular hypotonia (abnormally low muscle tone).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/346841">Feature record</a> | <a href="/medgen?term=%22Generalized%20hypotonia%22%5BClinical%20Features%5D%20OR%20346841%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_1644158"><div><strong>Microcephaly</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1644158</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C4551563</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Finding</dd></dl></div></div></div>
<div class="spaceAbove">Head circumference below 2 standard deviations below the mean for age and gender.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/1644158">Feature record</a> | <a href="/medgen?term=%22Microcephaly%22%5BClinical%20Features%5D%20OR%201644158%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_6979"><div><strong>Hypoglycemia</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>6979</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0020615</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">A decreased concentration of glucose in the blood.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/6979">Feature record</a> | <a href="/medgen?term=%22Hypoglycemia%22%5BClinical%20Features%5D%20OR%206979%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_120555"><div><strong>Aplasia of the nose</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>120555</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0265740</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Complete absence of all nasal structures.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/120555">Feature record</a> | <a href="/medgen?term=%22Aplasia%20of%20the%20nose%22%5BClinical%20Features%5D%20OR%20120555%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_146898"><div><strong>Tessier cleft</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>146898</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0685787</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">A congenital malformation with a cleft (gap or opening) in the face.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/146898">Feature record</a> | <a href="/medgen?term=%22Tessier%20cleft%22%5BClinical%20Features%5D%20OR%20146898%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_342454"><div><strong>Median cleft upper lip</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>342454</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1850256</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">A type of cleft lip presenting as a midline (median) gap in the upper lip.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/342454">Feature record</a> | <a href="/medgen?term=%22Median%20cleft%20upper%20lip%22%5BClinical%20Features%5D%20OR%20342454%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_340670"><div><strong>Median cleft palate</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>340670</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1850968</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Cleft palate of the midline of the palate.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/340670">Feature record</a> | <a href="/medgen?term=%22Median%20cleft%20palate%22%5BClinical%20Features%5D%20OR%20340670%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_339938"><div><strong>Midface retrusion</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>339938</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1853242</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Anatomical Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/339938">Feature record</a> | <a href="/medgen?term=%22Midface%20retrusion%22%5BClinical%20Features%5D%20OR%20339938%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_1684306"><div><strong>Proboscis</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1684306</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C5194070</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">A fleshy, tube-like structure usually located in the midline of the face or just to one side of the midline.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/1684306">Feature record</a> | <a href="/medgen?term=%22Proboscis%22%5BClinical%20Features%5D%20OR%201684306%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_8349"><div><strong>Diabetes insipidus</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>8349</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0011848</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/8349">Feature record</a> | <a href="/medgen?term=%22Diabetes%20insipidus%22%5BClinical%20Features%5D%20OR%208349%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_337539"><div><strong>Adrenal hypoplasia</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>337539</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1846223</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Pathologic Function</dd></dl></div></div></div>
<div class="spaceAbove">Developmental hypoplasia of the adrenal glands.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/337539">Feature record</a> | <a href="/medgen?term=%22Adrenal%20hypoplasia%22%5BClinical%20Features%5D%20OR%20337539%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_10033"><div><strong>Microphthalmia</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>10033</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0026010</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/10033">Feature record</a> | <a href="/medgen?term=%22Microphthalmia%22%5BClinical%20Features%5D%20OR%2010033%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_78617"><div><strong>Holoprosencephaly 1</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>78617</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information."><span class="highlight" style="background-color:">C0266667</span></a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context.&#13; Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity.&#13; See also schizencephaly (269160), which may be part of the phenotypic spectrum of HPE.&#13; Genetic Heterogeneity of Holoprosencephaly&#13; Several loci for holoprosencephaly have been mapped to specific chromosomal sites and the molecular defects in some cases of HPE have been identified. Holoprosencephaly-1 (HPE1) maps to chromosome 21q22. See also HPE2 (157170), caused by mutation in the SIX3 gene (603714) on 2p21; HPE3 (142945), caused by mutation in the SHH gene (600725) on 7q36; HPE4 (142946), caused by mutation in the TGIF gene (602630) on 18p11; HPE5 (609637), caused by mutation in the ZIC2 gene (603073) on 13q32; HPE6 (605934), mapped to 2q37; HPE7 (610828), caused by mutation in the PTCH1 gene (601309) on 9q22; HPE8 (609408), mapped to 14q13; HPE9 (610829), caused by mutation in the GLI2 gene (165230) on 2q14; HPE10 (612530), mapped to 1q41-q42; HPE11 (614226), caused by mutation in the CDON gene (608707) on 11q24; HPE12 (618500), caused by mutation in the CNOT1 gene (604917) on 16q21; HPE13 (301043), caused by mutation in the STAG2 gene (300826) on Xq25; and HPE14 (619895), caused by mutation in the PLCH1 gene (612835) on 3q25.&#13; Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE.&#13; Mutations in genes involved in the multiprotein cohesin complex, including STAG2, have been shown to be involved in midline brain defects such as HPE. Mutations in some of those genes cause Cornelia de Lange syndrome (CDLS; see 122470), and some patients with severe forms of CDLS may have midline brain defects. See, for example, CDLS2 (300590), CDLS3 (610759), and CDLS4 (614701).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/78617">Feature record</a> | <a href="/medgen?term=%22Holoprosencephaly%201%22%5BClinical%20Features%5D%20OR%2078617%5Buid%5D">Search on this feature</a></div></div>
<div class="divPopper rprt" id="clin_96107"><div><strong>Hypotelorism</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>96107</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0424711</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Finding</dd></dl></div></div></div>
<div class="spaceAbove">Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/96107">Feature record</a> | <a href="/medgen?term=%22Hypotelorism%22%5BClinical%20Features%5D%20OR%2096107%5Buid%5D">Search on this feature</a></div></div><div class="TreeLite" data-jigconfig="closed: 1"><div class="concept-def"><a class="small" href="#" onclick="jQuery(&quot;.TreeLite&quot;,&quot;#ID_102&quot;).TreeLite().openAll(); return false;">Show all</a><a class="small" href="#" onclick="jQuery(&quot;.TreeLite&quot;,&quot;#ID_102&quot;).TreeLite().closeAll(); return false;">Hide all</a></div><ul><li><span class="TLline">Abnormality of head or neck</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_120555" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Aplasia of the nose</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_340670" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Median cleft palate</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_342454" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Median cleft upper lip</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_339938" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Midface retrusion</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_1684306" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Proboscis</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_146898" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Tessier cleft</a></span></li></ul></li><li><span class="TLline">Abnormality of metabolism/homeostasis</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_6979" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Hypoglycemia</a></span></li></ul></li><li><span class="TLline">Abnormality of the cardiovascular system</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_56289" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Single ventricle</a></span></li></ul></li><li><span class="TLline">Abnormality of the endocrine system</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_337539" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Adrenal hypoplasia</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_8349" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Diabetes insipidus</a></span></li></ul></li><li><span class="TLline">Abnormality of the eye</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_78617" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Holoprosencephaly 1</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_96107" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Hypotelorism</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_10033" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Microphthalmia</a></span></li></ul></li><li><span class="TLline">Abnormality of the genitourinary system</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_1633603" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Micropenis</a></span></li></ul></li><li><span class="TLline">Abnormality of the musculoskeletal system</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_346841" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Generalized hypotonia</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_1644158" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Microcephaly</a></span></li></ul></li><li><span class="TLline">Abnormality of the nervous system</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_140909" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Alobar holoprosencephaly</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_120578" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Cerebellar hypoplasia</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_104498" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Corpus callosum, agenesis of</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_452352" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Ethmocephaly</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_107838" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Global developmental delay</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_811461" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Intellectual disability</a></span></li><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_20693" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Seizure</a></span></li></ul></li><li><span class="TLline">Growth abnormality</span><ul><li class="TLline">
<span class="TLline"><a title="click for more information" class="jig-ncbipopper" href="#clin_87607" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Short stature</a></span></li></ul></li></ul></div></div>
</div>
<div class="portlet mgSection" id="ID_118">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Term_Hierarchy">Term Hierarchy</h1><a sid="118" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln HierarchyGTR"><div class="jig-ncbitabs"><ul><li><a href="#tabGTR">GTR</a></li><li><a href="#tabMGEN">MeSH</a></li></ul><div id="tabGTR"><div class="search_result"><div class="rprts"><div class="chiclet_legend"><span class="chiclet_list" style="position:static;"><span title="Clinical test" class="chiclet Ccolor round">C</span><span>Clinical test,  </span><span title="Research test" class="chiclet Rcolor round">R</span><span>Research test,  </span><span title="OMIM" class="chiclet Ocolor ">O</span><span>OMIM,  </span><span title="GeneReview" class="chiclet Gcolor">G</span><span><em>GeneReviews</em>,  </span><span title="ClinVar" class="chiclet Vcolor">V</span><span>ClinVar  </span></span></div><div id="hierarchy" class="margin_t1"><div class="ds_tree"><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C0079541[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=38214">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=38214" target="_blank" href="/omim/236100">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=38214">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=38214" ref="ncbi_uid=38214">V</a></span></span><span class="TLline"><a href="/medgen/38214" ref="tree=GTR&amp;ncbi_uid=38214&amp;link_uid=38214" title="View MedGen record for 'Holoprosencephaly sequence'">Holoprosencephaly sequence</a></span><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C0265242[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=78541">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=78541" target="_blank" href="/omim/167420">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=78541">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=78541" ref="ncbi_uid=78541">V</a></span></span><span class="TLline"><a href="/medgen/78541" ref="tree=GTR&amp;ncbi_uid=78541&amp;link_uid=78541" title="View MedGen record for 'Agnathia-otocephaly complex'">Agnathia-otocephaly complex</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C2675857[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=382704">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=382704" target="_blank" href="/omim/612530">O</a></span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=382704" ref="ncbi_uid=382704">V</a></span></span><span class="TLline"><a href="/medgen/382704" ref="tree=GTR&amp;ncbi_uid=382704&amp;link_uid=382704" title="View MedGen record for 'Chromosome 1q41-q42 deletion syndrome'">Chromosome 1q41-q42 deletion syndrome</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1845146[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=335111">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=335111" target="_blank" href="/omim/136350">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/?term=(NBK1530%20OR%20NBK349073)%20AND%20gene%5Bbook%5D&amp;showtype=onebook" ref="ncbi_uid=335111">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=335111" ref="ncbi_uid=335111">V</a></span></span><span class="TLline"><a href="/medgen/335111" ref="tree=GTR&amp;ncbi_uid=335111&amp;link_uid=335111" title="View MedGen record for 'Hartsfield-Bixler-Demyer syndrome'">Hartsfield-Bixler-Demyer syndrome</a></span></li><li class="matched_ds"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C0266667[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=78617">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=78617" target="_blank" href="/omim/236100">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=78617">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=78617" ref="ncbi_uid=78617">V</a></span></span><span class="TLline">Holoprosencephaly 1</span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1834877[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=322517">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=322517" target="_blank" href="/omim/157170">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=322517">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=322517" ref="ncbi_uid=322517">V</a></span></span><span class="TLline"><a href="/medgen/322517" ref="tree=GTR&amp;ncbi_uid=322517&amp;link_uid=322517" title="View MedGen record for 'Holoprosencephaly 2'">Holoprosencephaly 2</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1840529[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=327125">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=327125" target="_blank" href="/omim/142945">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=327125">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=327125" ref="ncbi_uid=327125">V</a></span></span><span class="TLline"><a href="/medgen/327125" ref="tree=GTR&amp;ncbi_uid=327125&amp;link_uid=327125" title="View MedGen record for 'Holoprosencephaly 3'">Holoprosencephaly 3</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1840528[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=374488">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=374488" target="_blank" href="/omim/142946">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=374488">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=374488" ref="ncbi_uid=374488">V</a></span></span><span class="TLline"><a href="/medgen/374488" ref="tree=GTR&amp;ncbi_uid=374488&amp;link_uid=374488" title="View MedGen record for 'Holoprosencephaly 4'">Holoprosencephaly 4</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1864827[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=355304">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=355304" target="_blank" href="/omim/603073">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=355304">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=355304" ref="ncbi_uid=355304">V</a></span></span><span class="TLline"><a href="/medgen/355304" ref="tree=GTR&amp;ncbi_uid=355304&amp;link_uid=355304" title="View MedGen record for 'Holoprosencephaly 5'">Holoprosencephaly 5</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1853830[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=342979">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=342979" target="_blank" href="/omim/605934">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=342979">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/342979" ref="tree=GTR&amp;ncbi_uid=342979&amp;link_uid=342979" title="View MedGen record for 'Holoprosencephaly 6'">Holoprosencephaly 6</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1835820[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=372134">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=372134" target="_blank" href="/omim/601309">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=372134">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=372134" ref="ncbi_uid=372134">V</a></span></span><span class="TLline"><a href="/medgen/372134" ref="tree=GTR&amp;ncbi_uid=372134&amp;link_uid=372134" title="View MedGen record for 'Holoprosencephaly 7'">Holoprosencephaly 7</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1836254[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=322873">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=322873" target="_blank" href="/omim/609408">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=322873">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/322873" ref="tree=GTR&amp;ncbi_uid=322873&amp;link_uid=322873" title="View MedGen record for 'Holoprosencephaly 8'">Holoprosencephaly 8</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1835819[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=324369">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=324369" target="_blank" href="/omim/165230">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=324369">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=324369" ref="ncbi_uid=324369">V</a></span></span><span class="TLline"><a href="/medgen/324369" ref="tree=GTR&amp;ncbi_uid=324369&amp;link_uid=324369" title="View MedGen record for 'Holoprosencephaly 9'">Holoprosencephaly 9</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=441620">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/441620" ref="tree=GTR&amp;ncbi_uid=441620&amp;link_uid=441620" title="View MedGen record for 'Holoprosencephaly caudal dysgenesis'">Holoprosencephaly caudal dysgenesis</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=441187">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/441187" ref="tree=GTR&amp;ncbi_uid=441187&amp;link_uid=441187" title="View MedGen record for 'Holoprosencephaly deletion 2p'">Holoprosencephaly deletion 2p</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=441188">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/441188" ref="tree=GTR&amp;ncbi_uid=441188&amp;link_uid=441188" title="View MedGen record for 'Holoprosencephaly ectrodactyly cleft lip palate'">Holoprosencephaly ectrodactyly cleft lip palate</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=441189">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/441189" ref="tree=GTR&amp;ncbi_uid=441189&amp;link_uid=441189" title="View MedGen record for 'Holoprosencephaly radial heart renal anomalies'">Holoprosencephaly radial heart renal anomalies</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=343987" target="_blank" href="/omim/610680">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=343987">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/343987" ref="tree=GTR&amp;ncbi_uid=343987&amp;link_uid=343987" title="View MedGen record for 'Holoprosencephaly, recurrent infections, and monocytosis'">Holoprosencephaly, recurrent infections, and monocytosis</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=330464" target="_blank" href="/omim/601370">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=330464">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/330464" ref="tree=GTR&amp;ncbi_uid=330464&amp;link_uid=330464" title="View MedGen record for 'Holoprosencephaly-craniosynostosis syndrome'">Holoprosencephaly-craniosynostosis syndrome</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=336097" target="_blank" href="/omim/306990">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=336097">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=336097" ref="ncbi_uid=336097">V</a></span></span><span class="TLline"><a href="/medgen/336097" ref="tree=GTR&amp;ncbi_uid=336097&amp;link_uid=336097" title="View MedGen record for 'Holoprosencephaly-hypokinesia-congenital contractures syndrome'">Holoprosencephaly-hypokinesia-congenital contractures syndrome</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=340382" target="_blank" href="/omim/264480">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=340382">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/340382" ref="tree=GTR&amp;ncbi_uid=340382&amp;link_uid=340382" title="View MedGen record for 'Holoprosencephaly-postaxial polydactyly syndrome'">Holoprosencephaly-postaxial polydactyly syndrome</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet unavailable round" title="Clinical test">C</span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=343380" target="_blank" href="/omim/245552">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1530/" ref="ncbi_uid=343380">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/343380" ref="tree=GTR&amp;ncbi_uid=343380&amp;link_uid=343380" title="View MedGen record for 'Lambotte syndrome'">Lambotte syndrome</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN120371[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=468539">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/468539" ref="tree=GTR&amp;ncbi_uid=468539&amp;link_uid=468539" title="View MedGen record for 'NODAL-Related Holoprosencephaly'">NODAL-Related Holoprosencephaly</a></span></li></ul></li></ul></div></div></div></div></div><div id="tabMGEN"><div class="ds_tree"><ul><li><span class="TLline"><a href="/medgen/867443" ref="tree=MeSH" title="MedGen record for Phenotypic abnormality">Phenotypic abnormality</a></span><ul><li><span class="TLline"><a href="/medgen/1370071" ref="tree=MeSH" title="MedGen record for Abnormality of the eye">Abnormality of the eye</a></span><ul><li><span class="TLline"><a href="/medgen/868526" ref="tree=MeSH" title="MedGen record for Abnormal eye morphology">Abnormal eye morphology</a></span><ul><li><span class="TLline"><a href="/medgen/867563" ref="tree=MeSH" title="MedGen record for Abnormality of globe location">Abnormality of globe location</a></span><ul><li><span class="matched_ds">Holoprosencephaly 1</span></li></ul></li></ul></li></ul></li></ul></li></ul></div></div></div></div>
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Conditions_with_this_feature">Conditions with this feature</h1><a sid="112" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
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<div class="divPopper rprt" id="rdis_78617"><div><strong>Holoprosencephaly 1</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>78617</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information."><span class="highlight" style="background-color:">C0266667</span></a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context.&#13; Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity.&#13; See also schizencephaly (269160), which may be part of the phenotypic spectrum of HPE.&#13; Genetic Heterogeneity of Holoprosencephaly&#13; Several loci for holoprosencephaly have been mapped to specific chromosomal sites and the molecular defects in some cases of HPE have been identified. Holoprosencephaly-1 (HPE1) maps to chromosome 21q22. See also HPE2 (157170), caused by mutation in the SIX3 gene (603714) on 2p21; HPE3 (142945), caused by mutation in the SHH gene (600725) on 7q36; HPE4 (142946), caused by mutation in the TGIF gene (602630) on 18p11; HPE5 (609637), caused by mutation in the ZIC2 gene (603073) on 13q32; HPE6 (605934), mapped to 2q37; HPE7 (610828), caused by mutation in the PTCH1 gene (601309) on 9q22; HPE8 (609408), mapped to 14q13; HPE9 (610829), caused by mutation in the GLI2 gene (165230) on 2q14; HPE10 (612530), mapped to 1q41-q42; HPE11 (614226), caused by mutation in the CDON gene (608707) on 11q24; HPE12 (618500), caused by mutation in the CNOT1 gene (604917) on 16q21; HPE13 (301043), caused by mutation in the STAG2 gene (300826) on Xq25; and HPE14 (619895), caused by mutation in the PLCH1 gene (612835) on 3q25.&#13; Wallis and Muenke (2000) gave an overview of mutations in holoprosencephaly. They indicated that at least 12 different loci had been associated with HPE.&#13; Mutations in genes involved in the multiprotein cohesin complex, including STAG2, have been shown to be involved in midline brain defects such as HPE. Mutations in some of those genes cause Cornelia de Lange syndrome (CDLS; see 122470), and some patients with severe forms of CDLS may have midline brain defects. See, for example, CDLS2 (300590), CDLS3 (610759), and CDLS4 (614701).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/78617">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_322517"><div><strong>Holoprosencephaly 2</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>322517</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1834877</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">A rare disorder characterized by the partial separation of the cerebral hemispheres. It is associated with mutations in the SIX3 gene.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/322517">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_326686"><div><strong>Solitary median maxillary central incisor syndrome</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>326686</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1840235</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Congenital Abnormality</dd></dl></div></div></div>
<div class="spaceAbove">Solitary median maxillary central incisor (SMMCI) may occur as an isolated anomaly or with various associated features, primarily short stature, choanal atresia, midnasal stenosis, and holoprosencephaly (Hall et al., 1997).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/326686">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_327125"><div><strong>Holoprosencephaly 3</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>327125</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1840529</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">Any holoprosencephaly in which the cause of the disease is a mutation in the SHH gene.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/327125">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_340382"><div><strong>Holoprosencephaly-postaxial polydactyly syndrome</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>340382</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C1849649</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">Holoprosencephaly-postaxial polydactyly syndrome associates, in chromosomally normal neonates, holoprosencephaly, severe facial dysmorphism, postaxial polydactyly and other congenital abnormalities, suggestive of trisomy 13. Incidence is unknown. Dysmorphic features include hypotelorism, severe eye anomalies such as microphthalmia or anophthalmia, premaxillary region aplasia and cleft lip and palate. Congenital cardiac anomalies are common. The condition seems to be inherited as an autosomal recessive trait. Prognosis is poor.</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/340382">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_1714826"><div><strong>Holoprosencephaly 13, X-linked</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1714826</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C5393308</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">X-linked holoprosencephaly-13 (HPE13) is a neurologic disorder characterized by midline developmental defects that mainly affect the brain and craniofacial structure. The severity and manifestations are variable: some patients may have full alobar HPE with cyclopia, whereas others have semilobar HPE or septooptic dysplasia. Dysmorphic features include microcephaly, hypotelorism, low-set ears, micrognathia, and cleft lip/palate. Patients with a more severe phenotype may die in the newborn period, whereas those with a less severe phenotype show global developmental delay. Additional variable features include congenital heart defects and vertebral anomalies. Phenotypic variability may be related to the type of mutation, X-inactivation status, and possible incomplete penetrance. The STAG2 protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; HPE13 can thus be classified as a 'cohesinopathy' (summary by Kruszka et al., 2019).&#13; For a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/1714826">Condition Record</a></div></div>
<div class="divPopper rprt" id="rdis_1811868"><div><strong>Holoprosencephaly 14</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>1811868</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C5676994</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Disease or Syndrome</dd></dl></div></div></div>
<div class="spaceAbove">Holoprosencephaly-14 (HPE14) is an autosomal recessive condition characterized by severe developmental delay secondary to brain malformations within the holoprosencephaly spectrum (Drissi et al., 2022).&#13; For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).</div>
<div class="spaceAbove nowrap">See: <a href="/medgen/1811868">Condition Record</a></div></div>
<div class="hangingIndent"><a title="click for more information" class="jig-ncbipopper" href="#rdis_78617" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Holoprosencephaly 1</a></div>
<div class="hangingIndent"><a title="click for more information" class="jig-ncbipopper" href="#rdis_1714826" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Holoprosencephaly 13, X-linked</a></div>
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<div class="portlet mgSection" id="ID_105">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Professional_guidelines">Professional guidelines</h1><a sid="105" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><h3 class="subhead">PubMed<a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#guidelinesHelpPM"><img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a></h3>
<div class="nl"><a target="_blank" href="/pubmed/24754790">Cyclopamine: from cyclops lambs to cancer treatment.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Lee ST,
Welch KD,
Panter KE,
Gardner DR,
Garrossian M,
Chang CW</span><br />
<span class="medgenPMjournal">J Agric Food Chem</span>
2014 Jul 30;62(30):7355-62.
Epub 2014 Apr 22
doi: 10.1021/jf5005622.
<span class="bold">PMID: </span><a href="/pubmed/24754790" target="_blank">24754790</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(holoprosencephaly%201)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">See all (1)</a></div></div>
</div>
<div class="display-none help-popup" id="guidelinesHelpPM">These guidelines are articles in PubMed that match specific search criteria developed by MedGen to capture the most relevant practice guidelines. This list may not be comprehensive and may include broader topics as well. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div><div class="display-none help-popup" id="guidelinesHelpCurated">These guidelines are manually curated by the MedGen team
to supplement articles available in PubMed. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div>
<div class="portlet mgSection" id="ID_103">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Recent_clinical_studies">Recent clinical studies</h1><a sid="103" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><h3 class="subhead">Etiology</h3>
<div class="nl"><a target="_blank" href="/pubmed/20887106">Magnetic resonance imaging versus ultrasonography for the in utero evaluation of central nervous system anomalies.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Peruzzi P,
Corbitt RJ,
Raffel C</span><br />
<span class="medgenPMjournal">J Neurosurg Pediatr</span>
2010 Oct;6(4):340-5.
doi: 10.3171/2010.7.PEDS09511.
<span class="bold">PMID: </span><a href="/pubmed/20887106" target="_blank">20887106</a></div>
<div class="nl"><a target="_blank" href="/pubmed/15613950">Maternal obesity, gestational diabetes, and central nervous system birth defects.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Anderson JL,
Waller DK,
Canfield MA,
Shaw GM,
Watkins ML,
Werler MM</span><br />
<span class="medgenPMjournal">Epidemiology</span>
2005 Jan;16(1):87-92.
doi: 10.1097/01.ede.0000147122.97061.bb.
<span class="bold">PMID: </span><a href="/pubmed/15613950" target="_blank">15613950</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Holoprosencephaly%201%22%20AND%20Etiology%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div><h3 class="subhead">Diagnosis</h3>
<div class="nl"><a target="_blank" href="/pubmed/22752774">Role of foetal MRI in the evaluation of ischaemic-haemorrhagic lesions of the foetal brain.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Manganaro L,
Bernardo S,
La Barbera L,
Noia G,
Masini L,
Tomei A,
Fierro F,
Vinci V,
Sollazzo P,
Silvestri E,
Giancotti A,
Marini M</span><br />
<span class="medgenPMjournal">J Perinat Med</span>
2012 Apr 13;40(4):419-26.
doi: 10.1515/jpm-2011-0182.
<span class="bold">PMID: </span><a href="/pubmed/22752774" target="_blank">22752774</a></div>
<div class="nl"><a target="_blank" href="/pubmed/20887106">Magnetic resonance imaging versus ultrasonography for the in utero evaluation of central nervous system anomalies.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Peruzzi P,
Corbitt RJ,
Raffel C</span><br />
<span class="medgenPMjournal">J Neurosurg Pediatr</span>
2010 Oct;6(4):340-5.
doi: 10.3171/2010.7.PEDS09511.
<span class="bold">PMID: </span><a href="/pubmed/20887106" target="_blank">20887106</a></div>
<div class="nl"><a target="_blank" href="/pubmed/17139695">Familial diseases revealed by a fetal anomaly.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Robyr R,
Bernard JP,
Roume J,
Ville Y</span><br />
<span class="medgenPMjournal">Prenat Diagn</span>
2006 Dec;26(13):1224-34.
doi: 10.1002/pd.1593.
<span class="bold">PMID: </span><a href="/pubmed/17139695" target="_blank">17139695</a></div>
<div class="nl"><a target="_blank" href="/pubmed/8942027">Cerebellar dysgenesis in infants and children: an experience of 22 cases.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Yang MT,
Chen CH,
Chi CS,
Mak SC</span><br />
<span class="medgenPMjournal">Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi</span>
1996 Sep-Oct;37(5):342-8.
<span class="bold">PMID: </span><a href="/pubmed/8942027" target="_blank">8942027</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Holoprosencephaly%201%22%20AND%20Diagnosis%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (4)</a></div><h3 class="subhead">Therapy</h3>
<div class="nl"><a target="_blank" href="/pubmed/20887106">Magnetic resonance imaging versus ultrasonography for the in utero evaluation of central nervous system anomalies.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Peruzzi P,
Corbitt RJ,
Raffel C</span><br />
<span class="medgenPMjournal">J Neurosurg Pediatr</span>
2010 Oct;6(4):340-5.
doi: 10.3171/2010.7.PEDS09511.
<span class="bold">PMID: </span><a href="/pubmed/20887106" target="_blank">20887106</a></div>
<div class="nl"><a target="_blank" href="/pubmed/15613950">Maternal obesity, gestational diabetes, and central nervous system birth defects.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Anderson JL,
Waller DK,
Canfield MA,
Shaw GM,
Watkins ML,
Werler MM</span><br />
<span class="medgenPMjournal">Epidemiology</span>
2005 Jan;16(1):87-92.
doi: 10.1097/01.ede.0000147122.97061.bb.
<span class="bold">PMID: </span><a href="/pubmed/15613950" target="_blank">15613950</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Holoprosencephaly%201%22%20AND%20Therapy%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div><h3 class="subhead">Prognosis</h3>
<div class="nl"><a target="_blank" href="/pubmed/20887106">Magnetic resonance imaging versus ultrasonography for the in utero evaluation of central nervous system anomalies.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Peruzzi P,
Corbitt RJ,
Raffel C</span><br />
<span class="medgenPMjournal">J Neurosurg Pediatr</span>
2010 Oct;6(4):340-5.
doi: 10.3171/2010.7.PEDS09511.
<span class="bold">PMID: </span><a href="/pubmed/20887106" target="_blank">20887106</a></div>
<div class="nl"><a target="_blank" href="/pubmed/8942027">Cerebellar dysgenesis in infants and children: an experience of 22 cases.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Yang MT,
Chen CH,
Chi CS,
Mak SC</span><br />
<span class="medgenPMjournal">Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi</span>
1996 Sep-Oct;37(5):342-8.
<span class="bold">PMID: </span><a href="/pubmed/8942027" target="_blank">8942027</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Holoprosencephaly%201%22%20AND%20Prognosis%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div><h3 class="subhead">Clinical prediction guides</h3>
<div class="nl"><a target="_blank" href="/pubmed/8942027">Cerebellar dysgenesis in infants and children: an experience of 22 cases.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Yang MT,
Chen CH,
Chi CS,
Mak SC</span><br />
<span class="medgenPMjournal">Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi</span>
1996 Sep-Oct;37(5):342-8.
<span class="bold">PMID: </span><a href="/pubmed/8942027" target="_blank">8942027</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Holoprosencephaly%201%22%20AND%20Clinical%20prediction%20guides%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (1)</a></div></div>
</div>
</div></div></div></div></div></div></div>
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<div class="supplemental col three_col last">
<h2 class="offscreen_noflow">Supplemental Content</h2>
<div>
<!-- MedGen supplemental column starts here -->
<div class="rightCol mgCol">
<div class="portlet mgSection" id="ID_113">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Table_of_contents">Table of contents</h1><a sid="113" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul id="my-toc"></ul></div>
</div>
<div class="portlet mgSection" id="ID_106">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Genetic_Testing_Registry">Genetic Testing Registry</h1><a sid="106" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul><li><a href="/gtr/tests?term=C0266667%5bDISCUI%5d&amp;filter=method%3A2%5F8" target="_blank">Deletion/duplication analysis (5)</a></li>
<li><a href="/gtr/tests?term=C0266667%5bDISCUI%5d&amp;filter=method%3A2%5F7" target="_blank">Sequence analysis of the entire coding region (2)</a></li>
<li class="portletSeeAll portletSeeAllPad"><total><a href="/gtr/tests?term=C0266667%5bDISCUI%5d" target="_blank">See all (7)</a></total></li>
</ul></div>
</div>
<div class="portlet mgSection" id="ID_119">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Clinical_resources">Clinical resources</h1><a sid="119" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul><li><a href="https://www.omim.org/search?index=entry&amp;start=1&amp;limit=10&amp;sort=score%20desc&amp;field=number&amp;search=236100" target="_blank">OMIM</a></li><li><a href="http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=268936" target="_blank">Orphanet</a></li><li><a href="https://clinicaltrials.gov/search?cond=Holoprosencephaly%201" target="_blank">ClinicalTrials.gov</a></li></ul></div>
</div>
<div class="portlet mgSection" id="ID_121">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Practice_guidelines">Practice guidelines</h1><a sid="121" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul class="a_poppers"><li><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(holoprosencephaly%201)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">PubMed</a><div class="help-popup">See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div></li></ul></div>
</div>
<div class="portlet mgSection" id="ID_115">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Molecular_resources">Molecular resources</h1><a sid="115" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul><li><a href="https://catalog.coriell.org/Search?q=236100" target="_blank">Coriell Institute for Medical Research</a></li></ul></div>
</div>
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Consumer_resources">Consumer resources</h1><a sid="116" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul><li><a href="https://www.malacards.org/card/holoprosencephaly_1_2" target="_blank">MalaCards</a></li><li><a href="https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v:project=medlineplus&amp;query=Holoprosencephaly%201" target="_blank">MedlinePlus</a></li></ul></div>
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<div class="portlet_title">
<h3>Reviews</h3>
</div>
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<li>
<a href="/pubmed/20301702" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=1&amp;linkpostotal=3" target="_blank"><span class="gene_reviews">GeneReviews</span></a>
</li>
<li>
<a href="/pubmed/clinical?term=Holoprosencephaly%201" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=2&amp;linkpostotal=3" target="_blank">PubMed Clinical Queries</a>
</li>
<li>
<a href="/pubmed?term=Holoprosencephaly%201%20AND%20humans[mesh]%20AND%20review[publication%20type]" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=3&amp;linkpostotal=3" target="_blank">Reviews in PubMed</a>
</li>
</ul>
</div>
</div>
<!-- MedGen supplemental column ends here -->
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<h3>Related information</h3>
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<div class="portlet_content DiscoveryDbLinks">
<ul>
<li class="brieflinkpopper">
<a class="brieflinkpopperctrl" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=78617" ref="log$=recordlinks">ClinVar</a>
<div class="brieflinkpop offscreen_noflow">Related medical variations</div>
</li>
<li class="brieflinkpopper">
<a class="brieflinkpopperctrl" href="/gtr/tests?term=C0266667[DISCUI]" ref="log$=recordlinks">GTR</a>
<div class="brieflinkpop offscreen_noflow">Related information in GTR</div>
</li>
<li class="brieflinkpopper">
<a class="brieflinkpopperctrl" href="/gtr/tests?term=C0266667[DISCUI]&amp;test_type=Clinical" ref="log$=recordlinks">GTR(Clinical)</a>
<div class="brieflinkpop offscreen_noflow">Clinical tests in GTR</div>
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