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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MGI Mouse Phenotypes related to Holoprosencephaly:

36 (show all 16)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:000538810.5HCRT, MNX1, GLI1, CDON, DHCR7, SIX3
2MP:000537110.3ZIC2, SHH, GLI2, GLI1, CDON, FGF8
3MP:000538210.3ZIC5, ZIC2, FOXH1, SHH, GLI2, CDON
4MP:000538110.3FOXH1, SHH, MNX1, GLI2, GLI1, CDON
5MP:000538010.2ZIC5, ZIC2, FOXH1, SHH, GLI2, GLI1
6MP:000538910.2GLI2, GLI1, FGF8, NODAL, PTCH1, TGIF1
7MP:000536910.2HCRT, SHH, FOXH1, ZIC1, MNX1, GLI2
8MP:000539010.2SHH, ZIC2, ZIC5, ZIC1, GLI2, CDON
9MP:000539110.1ZIC5, SHH, GLI2, CDON, FGF8, SIX3
10MP:000538610.1SHH, ZIC2, ZIC4, ZIC5, ZIC1, HCRT
11MP:000537810.1HCRT, SHH, FOXH1, ZIC4, ZIC5, ZIC1
12MP:000538510.1HCRT, SHH, FOXH1, ZIC2, MNX1, CDON
13MP:001076810.1MNX1, SHH, FOXH1, ZIC2, ZIC4, ZIC5
14MP:000287310.1SHH, MNX1, GLI2, GLI1, FGF8, NODAL
15MP:000363110.0TGIF1, ZIC1, ZIC5, ZIC4, ZIC2, FOXH1
16MP:00053679.9FOXH1, SHH, GLI1, FGF8, DHCR7, PTCH1

Publications for Holoprosencephaly

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50PubMed
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Articles related to Holoprosencephaly:

(show top 50)    (show all 554)
idTitleAuthorsYear
1
Rescue of holoprosencephaly in fetal alcohol-exposed cdon mutant mice by reduced gene dosage of ptch1. (24244464)
2013
2
Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant geneA9gene interactions. (22310223)
2012
3
Oculo-auriculo-vertebral spectrum (OAVS) with large cerebral cyst: affinity to holoprosencephaly. (22992537)
2012
4
Exon trapping analysis of c.301-19GA >A A in intron 1 of the SHH gene in a patient with a microform of holoprosencephaly. (21044704)
2011
5
A novel heterozygous missense mutation G316D of SIX3 gene in a Brazilian patient with holoprosencephaly-like phenotype and Langerhans cell histiocytosis. (21368660)
2011
6
Sonographic diagnosis of brain malformations, part 2: holoprosencephaly - hydranencephaly - agenesis of septum pellucidum - schizencephaly - septo-optical dysplasia. (21117007)
2010
7
Genesis of teratogen-induced holoprosencephaly in mice. (20104601)
2010
8
Holoprosencephaly and ectrodactyly: Report of three new patients and review of the literature. (20104609)
2010
9
Abnormal sterol metabolism in holoprosencephaly. (20104605)
2010
10
The molecular genetics of holoprosencephaly. (20104595)
2010
11
3-D reconstruction of a human fetus with combined holoprosencephaly and cyclopia. (19563629)
2009
12
A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1. (19478089)
2009
13
Sensory function in severe semilobar holoprosencephaly. (19153870)
2009
14
Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. (18694563)
2008
15
Prenatal diagnosis of partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter) associated with abnormal sonographic findings of holoprosencephaly, orofacial clefts, pyelectasis and a unilateral duplex renal system. (18926951)
2008
16
Lobar holoprosencephaly in 18pter deletion resulting from the karyotype 45,X,-18,der(8;18)t(8; 18)(pter;p11.21). (19239091)
2008
17
Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly. (17468181)
2007
18
Prenatal diagnosis of alobar holoprosencephaly with cystic hygroma. (17197356)
2006
19
Prenatal diagnosis of holoprosencephaly with ethmocephaly via 3-dimensional sonography. (16788963)
2006
20
Holoprosencephaly: clinical evaluation on audiological and brainstem electrophysiological profiles. (16718676)
2006
21
Holoprosencephaly--report of two cases. (16083973)
2005
22
In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation. (15590697)
2005
23
Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. (16282375)
2005
24
Endocrine disorders associated with holoprosencephaly. (16355806)
2005
25
Lobar holoprosencephaly: prenatal MR diagnosis with postnatal MR correlation. (15849803)
2005
26
Middle interhemispheric variant of holoprosencephaly: a very mild clinical case. (15596788)
2004
27
Methanol exposure during gastrulation causes holoprosencephaly, facial dysgenesis, and cervical vertebral malformations in C57BL/6J mice. (15098201)
2004
28
SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. (12709790)
2003
29
Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly. (11857554)
2002
30
Neuroanatomy of holoprosencephaly as predictor of function: beyond the face predicting the brain. (12370462)
2002
31
Holoprosencephaly: genetic, neuroradiological, and clinical advances. (12523555)
2002
32
Molecular diagnosis of a novel heterozygous 268C-->T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis. (11810641)
2002
33
Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype. (11562938)
2001
34
Molecular genetics of holoprosencephaly. (10704430)
2000
35
Risk factors for cytogenetically normal holoprosencephaly in California: a population-based case-control study. (10710231)
2000
36
Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. (10441331)
1999
37
The molecular genetics of holoprosencephaly: a model of brain development for the next century. (10603005)
1999
38
First-trimester ultrasound diagnosis of holoprosencephaly: three case reports. (10380302)
1999
39
Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly, alobar holoprosencephaly and cebocephaly in a fetus. (9602489)
1998
40
Another holoprosencephaly locus at 7q21.2? (9678712)
1998
41
Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36 cause holoprosencephaly. (9254845)
1997
42
Cebocephaly, alobar holoprosencephaly, spina bifida, and sirenomelia in a stillbirth. (9132501)
1997
43
A unilateral cleft lip patient with holoprosencephaly. (9262780)
1997
44
Different proximal and distal rearrangements of chromosome 7q associated with holoprosencephaly. (9391882)
1997
45
Mutations in the human Sonic hedgehog gene cause holoprosencephaly. (8896572)
1996
46
A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. (7550324)
1995
47
Holoprosencephaly and primary craniosynostosis: the Genoa syndrome. (8291548)
1993
48
Holoprosencephaly and trisomy 13 in a fetus with maternal early gestational amphetamine abuse--a case report. (8207770)
1993
49
Lobar holoprosencephaly presenting as spastic diplegia. (3402680)
1988
50
A male infant with holoprosencephaly, associated with ring chromosome 21. (3568433)
1987

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, 4Cell Signaling Technology, 59Tocris Bioscience, 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 dihydrochloride5910.5DHCR7, GLI1, SHH
2cyclopamine44 5911.4PTCH1, GLI1, SHH
320(s)-hydroxycholesterol5910.4GLI1, SHH
4sant-15910.3GLI1, SHH
5zinc44 2411.2ZIC1, ZIC2, GLI2, GLI1, FGF8, PTCH1
6ciliobrevin a5910.1GLI1, SHH

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:06003210.8GLI2, GLI1
2ventral midline developmentGO:00741810.8GLI1, GLI2, SHH
3smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferationGO:02193810.8SHH, GLI2, GLI1
4hindgut morphogenesisGO:00744210.8SHH, GLI2
5floor plate formationGO:02150810.8FOXH1, GLI2
6formation of anatomical boundaryGO:04885910.8SHH, NODAL
7regulation of gastrulationGO:01047010.8NODAL, TGIF1
8nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetryGO:190016410.8FOXH1, NODAL
9smoothened signaling pathway involved in dorsal/ventral neural tube patterningGO:06083110.8GLI2, PTCH1
10mammary gland duct morphogenesisGO:06060310.8GLI2, PTCH1
11positive regulation of skeletal muscle tissue developmentGO:04864310.8SHH, CDON
12dorsal/ventral pattern formationGO:00995310.8SHH, GLI1, PTCH1, TGIF1
13spinal cord dorsal/ventral patterningGO:02151310.8SHH, GLI2
14cerebellar cortex morphogenesisGO:02169610.8GLI2, GLI1
15regulation of smoothened signaling pathwayGO:00858910.8ZIC1, GLI2, GLI1, PTCH1
16epidermal cell differentiationGO:00991310.8GLI2, GLI1
17somite developmentGO:06105310.8SHH, PTCH1
18lung developmentGO:03032410.8SHH, GLI2, GLI1, DHCR7
19branching involved in ureteric bud morphogenesisGO:00165810.8PTCH1, FGF8, SHH
20neural tube closureGO:00184310.7TGIF1, PTCH1, ZIC2, ZIC5
21heart loopingGO:00194710.7NODAL, FGF8, SHH, FOXH1
22smoothened signaling pathwayGO:00722410.7PTCH1, CDON, GLI1, GLI2, SHH
23positive regulation of T cell differentiation in thymusGO:03308910.7SHH, GLI2
24renal system developmentGO:07200110.7PTCH1, SHH
25cell migration involved in gastrulationGO:04207410.7FOXH1, NODAL
26brain developmentGO:00742010.7ZIC1, ZIC2, SIX3, NODAL, PTCH1
27pattern specification processGO:00738910.7GLI2, SHH, ZIC1
28positive regulation of neuron differentiationGO:04566610.7GLI2, CDON, TGIF1
29branching involved in salivary gland morphogenesisGO:06044510.7FGF8, SHH
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:00012210.7FOXH1, SHH, GLI2, NODAL, PTCH1, TGIF1
35positive regulation of transcription, DNA-dependentGO:04589310.7ZIC1, ZIC2, FOXH1, SHH, GLI2, GLI1
36pharyngeal system developmentGO:06003710.6FGF8, PTCH1
37spinal cord motor neuron differentiationGO:02152210.6SHH, PTCH1
38digestive tract morphogenesisGO:04854610.6GLI1, NODAL
39positive regulation of transcription from RNA polymerase II promoterGO:04594410.6FOXH1, SHH, GLI2, GLI1, CDON, SIX3
40cell fate specificationGO:00170810.6SHH, CDON
41hindbrain developmentGO:03090210.6SHH, GLI2
42positive regulation of smoothened signaling pathwayGO:04588010.6SHH, GLI1
43thyroid gland developmentGO:03087810.5SHH, FGF8
44male genitalia developmentGO:03053910.5SHH, FGF8
45osteoblast developmentGO:00207610.4SHH, GLI2
46pituitary gland developmentGO:02198310.4GLI1, GLI2
47embryonic pattern specificationGO:00988010.3SHH, NODAL
48proximal/distal pattern formationGO:00995410.1GLI1, GLI2

Molecular functions related to Holoprosencephaly according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1morphogen activityGO:01601510.5NODAL, SHH
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:04356510.2FOXH1, MNX1, GLI2, SIX3, TGIF1
6RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:00370510.1SIX3, GLI1, FOXH1

Products for genes affiliated with Holoprosencephaly

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Sources for Holoprosencephaly

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3CDC
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25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
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40NDF-RT
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