HPE
MCID: HLP001
MIFTS: 61

Holoprosencephaly (HPE) malady

Summaries for Holoprosencephaly

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42NIH Rare Diseases, 43NINDS, 63Wikipedia, 46OMIM, 19GeneReviews, 32MalaCards
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NIH Rare Diseases:42 Holoprosencephaly is an abnormality of brain development that also affects the head and face. normally, the brain divides into two halves (hemispheres) during early development. holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. there are four types of holoprosencephaly according to the degree of brain division. from most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (mihv). the most severely affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. in the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). holoprosencephaly can be caused by mutations in a single gene, chromosome abnormalities, or substances that cause birth defects (teratogens). last updated: 9/30/2010

MalaCards: Holoprosencephaly, also known as holoprosencephaly sequence, is related to cleft lip and microcephaly. An important gene associated with Holoprosencephaly is SIX3 (SIX homeobox 3), and among its related pathways are Glypican 3 network and Signaling by NODAL. The compounds ay 9944 dihydrochloride and cyclopamine have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and heart, and related mouse phenotypes are respiratory system and limbs/digits/tail.

NINDS:43 Holoprosencephaly is a disorder caused by the failure of the (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. In most cases of holoprosencephaly, the malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose, and upper lip.

Wikipedia:63 Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon... more...

Description from OMIM:46 609637, 157170, 142945, 610829, 236100 142946, 610828 more

GeneReviews summary for hpe-overview

Aliases & Classifications for Holoprosencephaly

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8Disease Ontology, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 43NINDS, 10DISEASES, 44Novoseek, 22GTR, 60UMLS, 46OMIM, 56SNOMED-CT, 34MeSH, 39NCIt
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Aliases & Descriptions:

holoprosencephaly 8 19 42 20 43 10 44
holoprosencephaly sequence 8 22
hirschsprung disease 1 60
hpe 42


External Ids:

Disease Ontology8 DOID:4621
SNOMED-CT56 30915001, 44519006
MeSH34 D016142
NCIt39 C74988

Related Diseases for Holoprosencephaly

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17GeneCards, 18GeneDecks
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Diseases in the Holoprosencephaly family:

Hpe6-Related Holoprosencephaly Ptch1-Related Holoprosencephaly
Shh-Related Holoprosencephaly Gli2-Related Holoprosencephaly
Hpe8-Related Holoprosencephaly Nodal-Related Holoprosencephaly
Foxh1-Related Holoprosencephaly Cdon-Related Holoprosencephaly
Zic2-Related Holoprosencephaly Six3-Related Holoprosencephaly
Tgif1-Related Holoprosencephaly Nonsyndromic Holoprosencephaly
Holoprosencephaly-2 Holoprosencephaly-9
Holoprosencephaly-6 Holoprosencephaly-3
Holoprosencephaly-7 Holoprosencephaly 11
Holoprosencephaly-5 Holoprosencephaly-8
Holoprosencephaly-4 Holoprosencephaly-1

Diseases related to Holoprosencephaly via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 139)
idRelated DiseaseScoreTop Affiliating Genes
1cleft lip30.5SHH, GLI2
2microcephaly30.2TGIF1, SHH
3microphthalmia30.2SIX3
4polydactyly30.2SHH, GLI2, GLI1, FGF8, PTCH1, DHCR7
5semilobar holoprosencephaly30.2SHH
6coloboma30.1SIX3
7smith-lemli-opitz syndrome30.1SHH, DHCR7
8moyamoya disease29.7TGIF1
9spina bifida29.7ZIC2, ZIC1
10nonsyndromic holoprosencephaly10.4
11hirschsprung's disease10.3
12cerebritis10.2
13cleft palate10.2
14genoa syndrome10.2
15single median maxillary central incisor10.2
16diabetes insipidus10.2
17holoprosencephaly caudal dysgenesis10.2
18craniosynostosis10.1
19hydrocephalus10.1
20steinfeld syndrome10.1
21morse-rawnsley-sargent syndrome10.1
22microcephaly, holoprosencephaly, and intrauterine growth retardation10.1
23hartsfield syndrome10.1
24holoprosencephaly - postaxial polydactyly10.1
25midline interhemispheric variant of holoprosencephaly10.1
26neuronitis10.1
27aicardi syndrome10.1
28down syndrome10.1
29congenital heart defect10.1
30hpe6-related holoprosencephaly10.1
31ptch1-related holoprosencephaly10.1
32shh-related holoprosencephaly10.1
33gli2-related holoprosencephaly10.1
34hpe8-related holoprosencephaly10.1
35zic2-related holoprosencephaly10.1
36six3-related holoprosencephaly10.1
37tgif1-related holoprosencephaly10.1
38agnathia-otocephaly complex10.1
39holoprosencephaly 1110.1
40congenital nasal pyriform aperture stenosis with holoprosencephaly10.1
41septopreoptic holoprosencephaly10.1
42lobar holoprosencephaly10.1
43alobar holoprosencephaly10.1
44pallister-hall syndrome10.0GLI1, SHH
45syndactyly10.0FGF8, DHCR7
46vacterl association10.0GLI2, SHH
47meningioma10.0TGIF1, PTCH1
48dandy-walker syndrome10.0ZIC1, ZIC4
49nevoid basal cell carcinoma syndrome10.0PTCH1, SHH, GLI1
50skin benign neoplasm10.0GLI1, GLI2, PTCH1

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to holoprosencephaly

Clinical Features for Holoprosencephaly

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46OMIM
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Clinical features from OMIM:

609637,157170,142945,610829,236100,142946,610828

Drugs & Therapeutics for Holoprosencephaly

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Holoprosencephaly

Drug clinical trials:

Search ClinicalTrials for Holoprosencephaly

Search NIH Clinical Center for Holoprosencephaly

Search CenterWatch for Holoprosencephaly

Genetic Tests for Holoprosencephaly

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20GeneTests, 22GTR
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Genetic tests related to Holoprosencephaly:

id Genetic test Affiliating Genes
1 Holoprosencephaly Multi-Gene Panels20
2 Holoprosencephaly20 ZIC2
3 Holoprosencephaly Sequence22

Anatomical Context for Holoprosencephaly

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32MalaCards
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MalaCards organs/tissues related to Holoprosencephaly:

32
Brain, Eye, Heart, Pituitary, Bone, Cortex, Cerebellum, Retina, Kidney, Pancreas, Fetal brain, Thalamus

Animal Models for Holoprosencephaly or affiliated genes

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36MGI
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Publications for Holoprosencephaly

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50PubMed
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Articles related to Holoprosencephaly:

(show top 50)    (show all 554)
idTitleAuthorsYear
1
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. (23812909)
2013
2
Semilobar Holoprosencephaly with Neurogenic Hypernatraemia: Two new cases. (23984038)
2013
3
Relatively high frequency of non-synonymous GLI2 variants in patients with congenital hypopituitarism without holoprosencephaly. (22967285)
2013
4
Airway management in an infant with alobar holoprosencephaly and cebocephaly associated with maternal diabetes mellitus. (23599105)
2013
5
Thick corpus callosum: a clue to the diagnosis of fetal septopreoptic holoprosencephaly? (22006531)
2012
6
A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3a88Mb deletion encompassing GLI2. (22106008)
2012
7
Prenatal ultrasound diagnosis of holoprosencephaly and associated anomalies. (23010458)
2012
8
Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway. (22383895)
2012
9
Microduplication of Xq24 and Hartsfield syndrome with holoprosencephaly, ectrodactyly, and clefting. (22887648)
2012
10
Two cases of single-stage lip and nostril reconstruction in holoprosencephaly. (21470822)
2011
11
Holoprosencephaly-diencephalic hamartoma: sequence or pleiotropy? (20034093)
2010
12
The unfolding clinical spectrum of holoprosencephaly due to mutations in SHH, ZIC2, SIX3 and TGIF genes. (20531442)
2010
13
Holoprosencephaly and craniosynostosis: A report of two siblings and review of the literature. (20104614)
2010
14
A preterm infant with semilobar holoprosencephaly and hydrocephalus: a case report. (20180992)
2010
15
Zic-associated holoprosencephaly: zebrafish Zic1 controls midline formation and forebrain patterning by regulating Nodal, Hedgehog, and retinoic acid signaling. (19528322)
2009
16
Prenatal MRI image of a fetus with semilobar holoprosencephaly. (21654965)
2008
17
Holoprosencephaly: an antenatally-diagnosed case series and subject review. (18695774)
2008
18
Mutations in the human SIX3 gene in holoprosencephaly are loss of function. (18791198)
2008
19
Middle interhemispheric variant of holoprosencephaly associated with bilateral perisylvian polymicrogyria. (18353069)
2008
20
Upper limb amelia, facial clefts, holoprosencephaly, and interrupted aortic arch. (18075831)
2007
21
Holoprosencephaly at 9 weeks 6 days in a triploid fetus: two- and 3-dimensional sonographic findings. (17324996)
2007
22
Functional analysis of mutations in TGIF associated with holoprosencephaly. (16962354)
2007
23
Midline "brain in brain": an unusual variant of holoprosencephaly with anterior prosomeric cortical dysplasia. (17103005)
2007
24
SIX3 mutations with holoprosencephaly. (17001667)
2006
25
Congenital holoprosencephaly with severe otocephaly in a rottweiler puppy. (16617045)
2006
26
Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: an animal model of holoprosencephaly. (15699650)
2005
27
Semilobar holoprosencephaly in a Morgan horse. (15954555)
2005
28
Phenotypic variability in human embryonic holoprosencephaly in the Kyoto Collection. (15329827)
2004
29
Bilateral persistent fetal vasculature associated with holoprosencephaly. (15305535)
2004
30
Holoprosencephaly presenting as membranous aplasia cutis and diabetes insipidus: report of one case. (15493741)
2004
31
Minimal clinical expression of the holoprosencephaly spectrum and of Currarino syndrome due to different cytogenetic rearrangements deleting the Sonic Hedgehog gene and the HLXB9 gene at 7q36.3. (15211664)
2004
32
Middle interhemispheric variant of holoprosencephaly associated with diffuse polymicrogyria. (12637288)
2003
33
Prenatal diagnosis of iniencephaly and alobar holoprosencephaly with trisomy 13 mosaicism: a case report. (12478643)
2002
34
Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures. (11827887)
2002
35
Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. (12395298)
2002
36
Problems in the definition of holoprosencephaly. (11745988)
2001
37
Airway obstruction due to a rudimentary premaxilla in holoprosencephaly. (11386438)
2001
38
Holoprosencephaly and split hand/foot: an additional case with this rare association. (11666003)
2001
39
Molecular mechanisms of holoprosencephaly. (10527664)
1999
40
Towards a greater understanding of the pathogenesis of holoprosencephaly. (10598051)
1999
41
Cyclopamine-induced holoprosencephaly and associated craniofacial malformations in the golden hamster: anatomic and molecular events. (10463269)
1998
42
De novo 7q36 deletion: breakpoint analysis and types of holoprosencephaly. (9450876)
1998
43
Holoprosencephaly. (9621381)
1998
44
Holoprosencephaly and cerebellar hypoplasia in a neonate with multiple congenital malformations. (9257477)
1997
45
Transverse limb defects, holoprosencephaly and neuronal heterotopia--a new syndrome? (9354847)
1997
46
Anatomy of the circle of Willis in three cases of human fetal synophthalmic holoprosencephaly. (9010572)
1996
47
Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. (8896571)
1996
48
Surgical treatment of patients with lobar holoprosencephaly: a personal note. (8467017)
1993
49
Holoprosencephaly Overview (20301702)
1993
50
In utero sonographic diagnosis of semilobar holoprosencephaly. (3914909)
1985

Genetic Variations for Holoprosencephaly

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Expression for genes affiliated with Holoprosencephaly

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Holoprosencephaly

Search GEO for disease gene expression data for Holoprosencephaly.

Pathways for genes affiliated with Holoprosencephaly

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37NCBI BioSystems Database, 53Reactome, 12EMD Millipore, 59Tocris Bioscience, 4Cell Signaling Technology, 29KEGG
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Compounds for genes affiliated with Holoprosencephaly

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59Tocris Bioscience, 44Novoseek, 24HMDB
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Compounds related to Holoprosencephaly according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1ay 9944 dihydrochloride5910.5SHH, GLI1, DHCR7
2cyclopamine44 5911.4SHH, GLI1, PTCH1
3sant-15910.4SHH, GLI1
420(s)-hydroxycholesterol5910.3GLI1, SHH
5zinc44 2411.2TGIF1, ZIC1, ZIC2, GLI2, GLI1, FGF8
6ciliobrevin a5910.1SHH, GLI1

GO Terms for genes affiliated with Holoprosencephaly

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16Gene Ontology
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Cellular components related to Holoprosencephaly according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1primary ciliumGO:07237210.4PTCH1, GLI1

Biological processes related to Holoprosencephaly according to GeneCards/GeneDecks:

(show all 48)
idNameGO IDScoreTop Affiliating Genes
1notochord regressionGO:06003210.8GLI1, GLI2
2ventral midline developmentGO:00741810.8GLI1, GLI2, SHH
3smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferationGO:02193810.8GLI1, GLI2, SHH
4hindgut morphogenesisGO:00744210.8SHH, GLI2
5floor plate formationGO:02150810.8GLI2, FOXH1
6regulation of gastrulationGO:01047010.8NODAL, TGIF1
7nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetryGO:190016410.8FOXH1, NODAL
8formation of anatomical boundaryGO:04885910.8SHH, NODAL
9smoothened signaling pathway involved in dorsal/ventral neural tube patterningGO:06083110.8GLI2, PTCH1
10positive regulation of skeletal muscle tissue developmentGO:04864310.8SHH, CDON
11mammary gland duct morphogenesisGO:06060310.8PTCH1, GLI2
12dorsal/ventral pattern formationGO:00995310.8TGIF1, PTCH1, SHH, GLI1
13spinal cord dorsal/ventral patterningGO:02151310.8GLI2, SHH
14epidermal cell differentiationGO:00991310.8GLI2, GLI1
15regulation of smoothened signaling pathwayGO:00858910.8GLI2, PTCH1, GLI1, ZIC1
16cerebellar cortex morphogenesisGO:02169610.8GLI1, GLI2
17somite developmentGO:06105310.8PTCH1, SHH
18lung developmentGO:03032410.8GLI2, SHH, DHCR7, GLI1
19branching involved in ureteric bud morphogenesisGO:00165810.8PTCH1, SHH, FGF8
20neural tube closureGO:00184310.7TGIF1, PTCH1, ZIC2, ZIC5
21positive regulation of T cell differentiation in thymusGO:03308910.7SHH, GLI2
22heart loopingGO:00194710.7FOXH1, SHH, NODAL, FGF8
23smoothened signaling pathwayGO:00722410.7PTCH1, CDON, GLI1, GLI2, SHH
24renal system developmentGO:07200110.7PTCH1, SHH
25cell migration involved in gastrulationGO:04207410.7FOXH1, NODAL
26brain developmentGO:00742010.7NODAL, ZIC2, ZIC1, PTCH1, SIX3
27pattern specification processGO:00738910.7ZIC1, SHH, GLI2
28positive regulation of neuron differentiationGO:04566610.7GLI2, TGIF1, CDON
29branching involved in salivary gland morphogenesisGO:06044510.7SHH, FGF8
30aorta morphogenesisGO:03590910.7FOXH1, FGF8
31negative regulation of androgen receptor signaling pathwayGO:06076610.7FOXH1, NODAL
32positive regulation of protein import into nucleusGO:04230710.7ZIC1, SHH
33dorsal/ventral neural tube patterningGO:02190410.7MNX1, SHH
34negative regulation of transcription from RNA polymerase II promoterGO:00012210.7TGIF1, GLI2, PTCH1, SHH, FOXH1, NODAL
35positive regulation of transcription, DNA-dependentGO:04589310.7ZIC1, GLI1, SHH, GLI2, FOXH1, ZIC2
36pharyngeal system developmentGO:06003710.6PTCH1, FGF8
37spinal cord motor neuron differentiationGO:02152210.6SHH, PTCH1
38digestive tract morphogenesisGO:04854610.6GLI1, NODAL
39positive regulation of transcription from RNA polymerase II promoterGO:04594410.6NODAL, SIX3, CDON, GLI1, GLI2, FOXH1
40cell fate specificationGO:00170810.6CDON, SHH
41hindbrain developmentGO:03090210.6GLI2, SHH
42osteoblast developmentGO:00207610.6GLI2, SHH
43male genitalia developmentGO:03053910.5FGF8, SHH
44positive regulation of smoothened signaling pathwayGO:04588010.5SHH, GLI1
45pituitary gland developmentGO:02198310.4GLI1, GLI2
46thyroid gland developmentGO:03087810.4FGF8, SHH
47embryonic pattern specificationGO:00988010.3NODAL, SHH
48proximal/distal pattern formationGO:00995410.1GLI1, GLI2

Molecular functions related to Holoprosencephaly according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1morphogen activityGO:01601510.5SHH, NODAL
2patched bindingGO:00511310.4SHH, PTCH1
3co-SMAD bindingGO:07041010.4TGIF1, FOXH1
4sequence-specific DNA binding transcription factor activityGO:00370010.3TGIF1, ZIC1, ZIC5, ZIC2, FOXH1, MNX1
5sequence-specific DNA bindingGO:04356510.2GLI2, FOXH1, MNX1, TGIF1, SIX3
6RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:00370510.1FOXH1, SIX3, GLI1

Products for genes affiliated with Holoprosencephaly

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3CDC
13ExPASy
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25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
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40NDF-RT
43NINDS
44Novoseek
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47OMIM via Orphanet
50PubMed
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57SNOMED-CT via Orphanet
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