HPE
MCID: HLP001
MIFTS: 64

Holoprosencephaly (HPE) malady

Genetic diseases, Rare diseases, Neuronal diseases, Endocrine diseases categories
Download this MalaCard

Summaries for Holoprosencephaly

About this section
Sources:
43NIH Rare Diseases, 44NINDS, 65Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
See all sources

Fully expand this MalaCard
NIH Rare Diseases:43 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 semilobar holoprosencephaly and lobar holoprosencephaly. An important gene associated with Holoprosencephaly is SIX3 (SIX homeobox 3), and among its related pathways are Transcription factors in neurogenesis and Glypican 3 network. The compounds 20(s)-hydroxycholesterol and ciliobrevin a have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and heart, and related mouse phenotypes are hearing/vestibular/ear and renal/urinary system.

NINDS:44 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:65 Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon... more...

Description from OMIM:47 157170, 142946, 236100, 609637, 610828 142945, 610829 more

GeneReviews summary for hpe-overview

Aliases & Classifications for Holoprosencephaly

About this section
Sources:
8Disease Ontology, 19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 44NINDS, 10DISEASES, 45Novoseek, 22GTR, 62UMLS, 47OMIM, 35MeSH, 40NCIt, 58SNOMED-CT
See all sources

Classifications:



Aliases & Descriptions:

holoprosencephaly 8 19 43 20 44 10 45
holoprosencephaly sequence 8 22
hirschsprung disease 1 62
hpe 43


External Ids:

Disease Ontology8 DOID:4621
SNOMED-CT58 30915001, 44519006
MeSH35 D016142
NCIt40 C74988

Related Diseases for Holoprosencephaly

About this section
Sources:
17GeneCards, 18GeneDecks
See all sources

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 174)
idRelated DiseaseScoreTop Affiliating Genes
1semilobar holoprosencephaly31.1SHH
2lobar holoprosencephaly31.0PTCH1
3single median maxillary central incisor30.5SHH
4cleft lip30.4SHH, GLI2
5microcephaly30.3TGIF1, SHH
6schizencephaly30.3SHH
7coloboma30.3SIX3
8polydactyly30.1SHH, PTCH1, GLI2, GLI1, DHCR7
9smith-lemli-opitz syndrome30.1DHCR7, SHH
10moyamoya disease29.9TGIF1
11spina bifida29.9ZIC2
12alobar holoprosencephaly10.7
13nonsyndromic holoprosencephaly10.4
14genoa syndrome10.3
15cerebritis10.2
16triploidy10.2
17hartsfield syndrome10.2
18diabetes insipidus10.2
19microphthalmia10.2
20holoprosencephaly caudal dysgenesis10.2
21steinfeld syndrome10.2
22septopreoptic holoprosencephaly10.2
23craniosynostosis10.1
24hydrocephalus10.1
25caudal regression syndrome10.1
26microcephaly, holoprosencephaly, and intrauterine growth retardation10.1
27morse-rawnsley-sargent syndrome10.1
28monosomy 18p10.1
29holoprosencephaly - postaxial polydactyly10.1
30midline interhemispheric variant of holoprosencephaly10.1
31aicardi syndrome10.1
32down syndrome10.1
33dysgnathia complex10.1
34encephalocele10.1
35holoprosencephaly, recurrent infections, and monocytosis10.1
36pseudotrisomy 13 syndrome10.1
37hpe6-related holoprosencephaly10.1
38ptch1-related holoprosencephaly10.1
39shh-related holoprosencephaly10.1
40gli2-related holoprosencephaly10.1
41hpe8-related holoprosencephaly10.1
42zic2-related holoprosencephaly10.1
43six3-related holoprosencephaly10.1
44tgif1-related holoprosencephaly10.1
45encephaloceles10.1
46agnathia-otocephaly complex10.1
47holoprosencephaly 1110.1
48congenital nasal pyriform aperture stenosis with holoprosencephaly10.1
49patau syndrome10.1SIX3, ZIC2
50pallister-hall syndrome10.0SHH, GLI1

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to holoprosencephaly

Symptoms for Holoprosencephaly

About this section
Sources:
47OMIM
See all sources


Clinical features from OMIM:

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

Drugs & Therapeutics for Holoprosencephaly

About this section
Sources:
42NIH Clinical Center, 6ClinicalTrials, 62UMLS, 41NDF-RT
See all sources

Drug clinical trials:

Search ClinicalTrials for Holoprosencephaly

Search NIH Clinical Center for Holoprosencephaly

Genetic Tests for Holoprosencephaly

About this section
Sources:
20GeneTests, 22GTR
See all sources

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

About this section
Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Holoprosencephaly:

33
Brain, Eye, Heart, Pituitary, Bone, Cortex, Cerebellum, Retina, Kidney, Pancreas, Fetal brain, Thalamus

Animal Models for Holoprosencephaly or affiliated genes

About this section
Sources:
37MGI
See all sources

MGI Mouse Phenotypes related to Holoprosencephaly:

37 (show all 21)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053778.9TGIF1, GLI2, SHH
2MP:00053678.7DHCR7, SHH, GLI1, PTCH1
3MP:00053698.4GLI2, PTCH1, SHH, DHCR7
4MP:00030128.3GLI1, SHH, GLI2, PTCH1
5MP:00053918.3CDON, GLI2, SIX3, PTCH1, SHH
6MP:00107718.2PTCH1, ZIC2, GLI2, SHH
7MP:00053798.2GLI2, GLI1, PTCH1, SHH
8MP:00053858.1SHH, PTCH1, TGIF1, DHCR7, CDON, ZIC2
9MP:00028738.0GLI1, GLI2, SHH, PTCH1, TGIF1
10MP:00053898.0GLI2, GLI1, PTCH1, TGIF1, SHH
11MP:00053847.5PTCH1, TGIF1, CDON, GLI1, GLI2, SHH
12MP:00053907.5TGIF1, ZIC2, SHH, CDON, GLI2, SIX3
13MP:00053887.2PTCH1, DHCR7, SIX3, GLI1, CDON, SHH
14MP:00053817.2PTCH1, DHCR7, SIX3, GLI2, GLI1, SHH
15MP:00053827.0CDON, GLI2, SIX3, DHCR7, TGIF1, PTCH1
16MP:00053787.0DHCR7, TGIF1, GLI2, GLI1, CDON, PTCH1
17MP:00053806.9TGIF1, CDON, GLI1, GLI2, SIX3, PTCH1
18MP:00053716.7GLI2, CDON, TGIF1, SHH, PTCH1, GLI1
19MP:00053866.7TGIF1, SHH, DHCR7, PTCH1, GLI2, GLI1
20MP:00036316.4GLI1, CDON, GLI2, SIX3, DHCR7, PTCH1
21MP:00107686.4GLI2, CDON, GLI1, SIX3, ZIC2, DHCR7

Publications for Holoprosencephaly

About this section
Sources:
52PubMed
See all sources

Articles related to Holoprosencephaly:

(show top 50)    (show all 548)
idTitleAuthorsYear
1
Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly and congenital heart defects. (24091065)
2014
2
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. (23812909)
2013
3
Holoprosencephaly: report of four cases and genotype-phenotype correlations. (23640411)
2013
4
Thick corpus callosum: a clue to the diagnosis of fetal septopreoptic holoprosencephaly? (22006531)
2012
5
Congenital partial arhinia: a rare malformation of the nose coexisting with holoprosencephaly. (23692731)
2012
6
Duplication of the ZIC2 gene is not associated with holoprosencephaly. (22105922)
2012
7
Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis. (21204232)
2011
8
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
9
Two cases of single-stage lip and nostril reconstruction in holoprosencephaly. (21470822)
2011
10
Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation. (20104607)
2010
11
Clinical image. Middle interhemispheric variant of holoprosencephaly. (19997726)
2010
12
Moebius syndrome and holoprosencephaly following exposure to misoprostol. (20933185)
2010
13
Lobar holoprosencephaly with a median cleft: case report. (19929095)
2009
14
Prenatal diagnosis and molecular analysis of triploidy in a fetus with intrauterine growth restriction, relative macrocephaly and holoprosencephaly. (19797034)
2009
15
Holoprosencephaly spectrum, ano/microphthalmia, and first branchial arch defects: evidence for a new disorder. (18049080)
2008
16
Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. (18694563)
2008
17
Prenatal MRI image of a fetus with semilobar holoprosencephaly. (21654965)
2008
18
Holoprosencephaly: an antenatally-diagnosed case series and subject review. (18695774)
2008
19
Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation. (18617531)
2008
20
Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly. (18338389)
2008
21
A triploid fetus further expands etiological heterogeneity in holoprosencephaly-diencephalic hamartoblastoma. (17497722)
2007
22
A mechanism for mutational inactivation of the homeodomain protein TGIF in holoprosencephaly. (17158784)
2007
23
Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly. (16503393)
2006
24
Links between abnormal brain structure and cognition in holoprosencephaly. (17138007)
2006
25
Central roles of the roof plate in telencephalic development and holoprosencephaly. (16855091)
2006
26
Anatomically corrected malposition of the great arteries in the setting of aortopulmonary window associated with holoprosencephaly. (16437257)
2006
27
White matter imaging in holoprosencephaly in children. (15021236)
2004
28
Lobar holoprosencephaly with vocal cord palsy. (12693788)
2003
29
Identification of unexpected parental Robertsonian (13q;14q) translocations following prenatal sonographic detection of holoprosencephaly. (12230460)
2002
30
Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly. (11857554)
2002
31
Mosaic trisomy 9 and lobar holoprosencephaly. (12210326)
2002
32
Hypodipsia-hypernatremia syndrome associated with holoprosencephaly in a child: a case report. (12405444)
2002
33
Prenatal diagnosis of agnathia-holoprosencephaly: three-dimensional imaging by helical computed tomography. (11180246)
2001
34
Problems in the definition of holoprosencephaly. (11745988)
2001
35
Holoprosencephaly: the Maastricht experience. (11693794)
2001
36
Holoprosencephaly (lobar form) associated with bilateral vocal cord palsy. (11785509)
2001
37
The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF. (10995736)
2000
38
Prenatal diagnosis of alobar holoprosencephaly by two-dimensional and three-dimensional ultrasound. (10820408)
2000
39
Heterotaxy-neural tube defect and holoprosencephaly occuring independently in two sib fetuses. (10340655)
1999
40
Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. (10441331)
1999
41
Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly, alobar holoprosencephaly and cebocephaly in a fetus. (9602489)
1998
42
Abnormal chromosome 18 in prenatal diagnosis with holoprosencephaly. (9316141)
1997
43
Midline interhemispheric fusion associated with atypical callosal dysgenesis: a mild type of holoprosencephaly. (8826753)
1996
44
Anterior callosal agenesis in mild, lobar holoprosencephaly. (7567274)
1995
45
Disorders of midline structures: holoprosencephaly, absence of corpus callosum, and Chiari malformations. (3078668)
1988
46
Aicardi syndrome with holoprosencephaly and cleft lip and palate. (3508052)
1987
47
Semilobar holoprosencephaly: embryologic, CSF dynamics and radiological considerations. (3962751)
1986
48
Acalvaria, holoprosencephaly, and facial dysmorphism syndrome. (3491120)
1986
49
An anatomical study of three cases of alobar holoprosencephaly. (7157189)
1982
50
FAMILIAL ALOBAR HOLOPROSENCEPHALY (ARHINENCEPHALY) WITH MEDIAN CLEFT LIP AND PALATE. REPORT OF PATIENT WITH 46 CHROMOSOMES. (14079950)
1963

Variations for Holoprosencephaly

About this section

Expression for genes affiliated with Holoprosencephaly

About this section
Sources:
2BioGPS, 15Gene Expression Omnibus DataSets
See all sources
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

About this section
Sources:
50PathCards, 12EMD Millipore, 38NCBI BioSystems Database, 30KEGG, 61Tocris Bioscience, 5Cell Signaling Technology, 60Thomson Reuters
See all sources

Compounds for genes affiliated with Holoprosencephaly

About this section
Sources:
61Tocris Bioscience, 45Novoseek, 29IUPHAR, 24HMDB, 11DrugBank
See all sources

Compounds related to Holoprosencephaly according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
120(s)-hydroxycholesterol619.6SHH, GLI1
2ciliobrevin a619.5SHH, GLI1
3sant-1619.4SHH, GLI1
4cyclopamine45 6110.2GLI1, PTCH1, SHH
5cholesterol45 29 24 1112.2DHCR7, TGIF1, SHH
6ay 9944 dihydrochloride619.1GLI1, DHCR7, SHH
7zinc45 248.5PTCH1, TGIF1, ZIC2, GLI2, GLI1

GO Terms for genes affiliated with Holoprosencephaly

About this section
Sources:
16Gene Ontology
See all sources

Cellular components related to Holoprosencephaly according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1primary ciliumGO:0723729.4GLI1, PTCH1

Biological processes related to Holoprosencephaly according to GeneCards/GeneDecks:

(show all 42)
idNameGO IDScoreTop Affiliating Genes
1somite developmentGO:06105310.1SHH, PTCH1
2renal system developmentGO:07200110.1PTCH1, SHH
3spinal cord motor neuron differentiationGO:02152210.0PTCH1, SHH
4positive regulation of skeletal muscle tissue developmentGO:04864310.0SHH, CDON
5cell fate specificationGO:0017089.9CDON, SHH
6embryonic limb morphogenesisGO:0303269.9SHH, PTCH1
7branching involved in ureteric bud morphogenesisGO:0016589.9PTCH1, SHH
8positive regulation of smoothened signaling pathwayGO:0458809.8GLI1, SHH
9hindgut morphogenesisGO:0074429.7GLI2, SHH
10brain developmentGO:0074209.7PTCH1, ZIC2, SIX3
11spinal cord dorsal/ventral patterningGO:0215139.7SHH, GLI2
12positive regulation of T cell differentiation in thymusGO:0330899.7GLI2, SHH
13neural tube closureGO:0018439.6ZIC2, TGIF1, PTCH1
14smoothened signaling pathway involved in dorsal/ventral neural tube patterningGO:0608319.6GLI2, PTCH1
15mammary gland duct morphogenesisGO:0606039.6PTCH1, GLI2
16hindbrain developmentGO:0309029.6GLI2, SHH
17osteoblast developmentGO:0020769.6SHH, GLI2
18regulation of cell proliferationGO:0421279.6DHCR7, SHH
19branching morphogenesis of an epithelial tubeGO:0487549.6GLI2, SHH
20embryonic digit morphogenesisGO:0427339.5GLI2, SHH
21notochord regressionGO:0600329.4GLI1, GLI2
22cerebellar cortex morphogenesisGO:0216969.4GLI2, GLI1
23negative regulation of canonical Wnt signaling pathwayGO:0900909.4GLI1, SHH
24epidermal cell differentiationGO:0099139.4GLI2, GLI1
25response to mechanical stimulusGO:0096129.4PTCH1, GLI2
26odontogenesis of dentin-containing toothGO:0424759.4SHH, GLI2
27proximal/distal pattern formationGO:0099549.3GLI1, GLI2
28pattern specification processGO:0073899.3SHH, GLI2
29anterior/posterior pattern specificationGO:0099529.3CDON, SHH
30pituitary gland developmentGO:0219839.3GLI2, GLI1
31positive regulation of DNA replicationGO:0457409.3GLI1, GLI2
32osteoblast differentiationGO:0016499.1GLI1, GLI2
33ventral midline developmentGO:0074189.1SHH, GLI2, GLI1
34smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferationGO:0219389.1SHH, GLI2, GLI1
35positive regulation of neuron differentiationGO:0456669.1TGIF1, GLI2, CDON
36dorsal/ventral pattern formationGO:0099539.1GLI1, TGIF1, PTCH1, SHH
37regulation of smoothened signaling pathwayGO:0085899.0PTCH1, GLI2, GLI1
38negative regulation of transcription from RNA polymerase II promoterGO:0001228.8SHH, PTCH1, TGIF1, GLI2
39positive regulation of transcription, DNA-templatedGO:0458938.7GLI1, GLI2, ZIC2, SHH
40lung developmentGO:0303248.6GLI1, GLI2, DHCR7, SHH
41positive regulation of transcription from RNA polymerase II promoterGO:0459448.3SHH, SIX3, GLI2, GLI1, CDON
42smoothened signaling pathwayGO:0072248.2CDON, GLI1, GLI2, PTCH1, SHH

Molecular functions related to Holoprosencephaly according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1patched bindingGO:0051139.7PTCH1, SHH
2RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:0037059.5GLI1, SIX3
3sequence-specific DNA bindingGO:0435658.6TGIF1, SIX3, GLI2
4chromatin bindingGO:0036828.5GLI1, GLI2, TGIF1

Products for genes affiliated with Holoprosencephaly

About this section
  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Holoprosencephaly

About this section
4CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
59SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet