HPE
MCID: HLP001
MIFTS: 68

Holoprosencephaly (HPE) malady

Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases categories

Summaries for Holoprosencephaly

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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 based summary: Holoprosencephaly, also known as holoprosencephaly sequence, is related to semilobar holoprosencephaly and lobar holoprosencephaly, and has symptoms including autosomal recessive inheritance, micropenis and hypotelorism. 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 sant-1 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: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:64 Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon... more...

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

GeneReviews summary for hpe-overview

Aliases & Classifications for Holoprosencephaly

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Holoprosencephaly, Aliases & Descriptions:

Name: Holoprosencephaly 31 9 20 42 21 43 11 44
Holoprosencephaly Sequence 9 23
 
Hpe 42


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases, Fetal diseases
Anatomical: Neuronal diseases


External Ids:

Disease Ontology9 DOID:4621
NCIt39 C74988
SNOMED-CT56 44519006, 30915001
MeSH34 D016142

Related Diseases for Holoprosencephaly

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Diseases in the Holoprosencephaly-3 family:

holoprosencephaly 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-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 181)
idRelated DiseaseScoreTop Affiliating Genes
1semilobar holoprosencephaly31.7SHH
2lobar holoprosencephaly31.6PTCH1
3schizencephaly30.9SHH
4single median maxillary central incisor30.9SHH
5coloboma30.7SIX3
6cleft lip30.5SHH, GLI2
7moyamoya disease30.4TGIF1
8smith-lemli-opitz syndrome30.3DHCR7, SHH
9microcephaly30.3TGIF1, SHH
10spina bifida30.3ZIC2
11polydactyly29.6SHH, PTCH1, GLI2, GLI1, DHCR7
12alobar holoprosencephaly10.7
13nonsyndromic holoprosencephaly10.5
14genoa syndrome10.3
15cerebritis10.3
16patau syndrome10.3SIX3, ZIC2
17triploidy10.2
18hartsfield syndrome10.2
19diabetes insipidus10.2
20microphthalmia10.2
21dysgnathia complex10.2
22holoprosencephaly caudal dysgenesis10.2
23morse-rawnsley-sargent syndrome10.2
24steinfeld syndrome10.2
25septopreoptic holoprosencephaly10.2
26pallister-hall syndrome10.2SHH, GLI1
27craniosynostosis10.2
28hydrocephalus10.2
29caudal regression syndrome10.2
30iniencephaly10.2
31microcephaly, holoprosencephaly, and intrauterine growth retardation10.2
32pseudotrisomy 13 syndrome10.2
33holoprosencephaly-310.2
34monosomy 18p10.2
35holoprosencephaly - postaxial polydactyly10.2
36midline interhemispheric variant of holoprosencephaly10.2
37down syndrome10.1
38neuronitis10.1
39aicardi syndrome10.1
40agenesis of the corpus callosum10.1
41encephalocele10.1
42holoprosencephaly, recurrent infections, and monocytosis10.1
43septo-optic dysplasia10.1
44agnathia-otocephaly complex10.1
45holoprosencephaly 1110.1
46congenital nasal pyriform aperture stenosis with holoprosencephaly10.1
47ameloblastoma10.1PTCH1, GLI1
48vacterl association10.1SHH, GLI2
49endotheliitis10.0
50nevoid basal cell carcinoma syndrome10.0GLI1, SHH, PTCH1

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to holoprosencephaly

Symptoms for Holoprosencephaly

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Clinical features from OMIM:

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

HPO human phenotypes related to Holoprosencephaly:

(show all 10)
id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 micropenis HP:0000054
3 hypotelorism HP:0000601
4 adrenal hypoplasia HP:0000835
5 seizures HP:0001250
6 hypoglycemia HP:0001943
7 facial cleft HP:0002006
8 alobar holoprosencephaly HP:0006988
9 median cleft lip and palate HP:0008501
10 cyclopia HP:0009914

Drugs & Therapeutics for Holoprosencephaly

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Drug clinical trials:

Search ClinicalTrials for Holoprosencephaly

Search NIH Clinical Center for Holoprosencephaly

Genetic Tests for Holoprosencephaly

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Genetic tests related to Holoprosencephaly:

id Genetic test Affiliating Genes
1 Holoprosencephaly Multi-Gene Panels21
2 Holoprosencephaly21 ZIC2
3 Holoprosencephaly Sequence23

Anatomical Context for Holoprosencephaly

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MalaCards organs/tissues related to Holoprosencephaly:

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

Animal Models for Holoprosencephaly or affiliated genes

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MGI Mouse Phenotypes related to Holoprosencephaly:

36 (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

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Articles related to Holoprosencephaly:

(show top 50)    (show all 566)
idTitleAuthorsYear
1
Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism. (24706429)
2014
2
Cyclopia, proboscis and alobar holoprosencephaly representative for trisomy 13. (25365860)
2014
3
Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly and congenital heart defects. (24091065)
2014
4
STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly. (25218063)
2014
5
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. (23812909)
2013
6
Holoprosencephaly: report of four cases and genotype-phenotype correlations. (23640411)
2013
7
Thick corpus callosum: a clue to the diagnosis of fetal septopreoptic holoprosencephaly? (22006531)
2012
8
Congenital partial arhinia: a rare malformation of the nose coexisting with holoprosencephaly. (23692731)
2012
9
Duplication of the ZIC2 gene is not associated with holoprosencephaly. (22105922)
2012
10
Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis. (21204232)
2011
11
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
12
Two cases of single-stage lip and nostril reconstruction in holoprosencephaly. (21470822)
2011
13
Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation. (20104607)
2010
14
Clinical image. Middle interhemispheric variant of holoprosencephaly. (19997726)
2010
15
Moebius syndrome and holoprosencephaly following exposure to misoprostol. (20933185)
2010
16
Sonographic diagnosis of brain malformations, part 2: holoprosencephaly - hydranencephaly - agenesis of septum pellucidum - schizencephaly - septo-optical dysplasia. (21117007)
2010
17
Lobar holoprosencephaly with a median cleft: case report. (19929095)
2009
18
Holoprosencephaly spectrum, ano/microphthalmia, and first branchial arch defects: evidence for a new disorder. (18049080)
2008
19
Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. (18694563)
2008
20
Prenatal MRI image of a fetus with semilobar holoprosencephaly. (21654965)
2008
21
Holoprosencephaly: an antenatally-diagnosed case series and subject review. (18695774)
2008
22
Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation. (18617531)
2008
23
Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly. (18338389)
2008
24
A triploid fetus further expands etiological heterogeneity in holoprosencephaly-diencephalic hamartoblastoma. (17497722)
2007
25
A mechanism for mutational inactivation of the homeodomain protein TGIF in holoprosencephaly. (17158784)
2007
26
Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly. (16503393)
2006
27
Links between abnormal brain structure and cognition in holoprosencephaly. (17138007)
2006
28
Central roles of the roof plate in telencephalic development and holoprosencephaly. (16855091)
2006
29
White matter imaging in holoprosencephaly in children. (15021236)
2004
30
Lobar holoprosencephaly with vocal cord palsy. (12693788)
2003
31
Identification of unexpected parental Robertsonian (13q;14q) translocations following prenatal sonographic detection of holoprosencephaly. (12230460)
2002
32
Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly. (11857554)
2002
33
Mosaic trisomy 9 and lobar holoprosencephaly. (12210326)
2002
34
Hypodipsia-hypernatremia syndrome associated with holoprosencephaly in a child: a case report. (12405444)
2002
35
Prenatal diagnosis of agnathia-holoprosencephaly: three-dimensional imaging by helical computed tomography. (11180246)
2001
36
Problems in the definition of holoprosencephaly. (11745988)
2001
37
Holoprosencephaly: the Maastricht experience. (11693794)
2001
38
The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF. (10995736)
2000
39
Prenatal diagnosis of alobar holoprosencephaly by two-dimensional and three-dimensional ultrasound. (10820408)
2000
40
Heterotaxy-neural tube defect and holoprosencephaly occuring independently in two sib fetuses. (10340655)
1999
41
Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. (10441331)
1999
42
Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly, alobar holoprosencephaly and cebocephaly in a fetus. (9602489)
1998
43
Abnormal chromosome 18 in prenatal diagnosis with holoprosencephaly. (9316141)
1997
44
Midline interhemispheric fusion associated with atypical callosal dysgenesis: a mild type of holoprosencephaly. (8826753)
1996
45
Anterior callosal agenesis in mild, lobar holoprosencephaly. (7567274)
1995
46
Disorders of midline structures: holoprosencephaly, absence of corpus callosum, and Chiari malformations. (3078668)
1988
47
Aicardi syndrome with holoprosencephaly and cleft lip and palate. (3508052)
1987
48
Semilobar holoprosencephaly: embryologic, CSF dynamics and radiological considerations. (3962751)
1986
49
Acalvaria, holoprosencephaly, and facial dysmorphism syndrome. (3491120)
1986
50
FAMILIAL ALOBAR HOLOPROSENCEPHALY (ARHINENCEPHALY) WITH MEDIAN CLEFT LIP AND PALATE. REPORT OF PATIENT WITH 46 CHROMOSOMES. (14079950)
1963

Variations for Holoprosencephaly

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Expression for genes affiliated with Holoprosencephaly

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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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Compounds for genes affiliated with Holoprosencephaly

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Sources:
60Tocris Bioscience, 44Novoseek, 29IUPHAR, 25HMDB, 12DrugBank
See all sources

Compounds related to Holoprosencephaly according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1sant-1609.6SHH, GLI1
2ciliobrevin a609.5GLI1, SHH
320(s)-hydroxycholesterol609.4GLI1, SHH
4cyclopamine44 6010.2SHH, PTCH1, GLI1
5cholesterol44 29 25 1212.2SHH, TGIF1, DHCR7
6ay 9944 dihydrochloride609.1SHH, DHCR7, GLI1
7zinc44 258.5PTCH1, TGIF1, ZIC2, GLI2, GLI1

GO Terms for genes affiliated with Holoprosencephaly

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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:07200110.1SHH, PTCH1
3spinal cord motor neuron differentiationGO:02152210.0PTCH1, SHH
4positive regulation of skeletal muscle tissue developmentGO:04864310.0CDON, SHH
5cell fate specificationGO:0017089.9CDON, SHH
6embryonic limb morphogenesisGO:0303269.9SHH, PTCH1
7branching involved in ureteric bud morphogenesisGO:0016589.9SHH, PTCH1
8positive regulation of smoothened signaling pathwayGO:0458809.8SHH, GLI1
9hindgut morphogenesisGO:0074429.7SHH, GLI2
10spinal cord dorsal/ventral patterningGO:0215139.7GLI2, SHH
11brain developmentGO:0074209.7SIX3, PTCH1, ZIC2
12positive regulation of T cell differentiation in thymusGO:0330899.7SHH, GLI2
13neural tube closureGO:0018439.6ZIC2, TGIF1, PTCH1
14smoothened signaling pathway involved in dorsal/ventral neural tube patterningGO:0608319.6PTCH1, GLI2
15mammary gland duct morphogenesisGO:0606039.6PTCH1, GLI2
16hindbrain developmentGO:0309029.6SHH, GLI2
17osteoblast developmentGO:0020769.6GLI2, SHH
18regulation of cell proliferationGO:0421279.6SHH, DHCR7
19branching morphogenesis of an epithelial tubeGO:0487549.6SHH, GLI2
20embryonic digit morphogenesisGO:0427339.5SHH, GLI2
21notochord regressionGO:0600329.4GLI2, GLI1
22epidermal cell differentiationGO:0099139.4GLI2, GLI1
23negative regulation of canonical Wnt signaling pathwayGO:0900909.4GLI1, SHH
24cerebellar cortex morphogenesisGO:0216969.4GLI2, GLI1
25response to mechanical stimulusGO:0096129.4GLI2, PTCH1
26pattern specification processGO:0073899.4GLI2, SHH
27proximal/distal pattern formationGO:0099549.3GLI1, GLI2
28odontogenesis of dentin-containing toothGO:0424759.3GLI2, SHH
29anterior/posterior pattern specificationGO:0099529.3CDON, SHH
30pituitary gland developmentGO:0219839.3GLI2, GLI1
31positive regulation of DNA replicationGO:0457409.3GLI2, GLI1
32osteoblast differentiationGO:0016499.1GLI2, GLI1
33ventral midline developmentGO:0074189.1GLI2, SHH, 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, CDON, GLI2
36dorsal/ventral pattern formationGO:0099539.1TGIF1, GLI1, SHH, PTCH1
37regulation of smoothened signaling pathwayGO:0085899.0PTCH1, GLI2, GLI1
38negative regulation of transcription from RNA polymerase II promoterGO:0001228.8GLI2, SHH, PTCH1, TGIF1
39positive regulation of transcription, DNA-templatedGO:0458938.7SHH, GLI2, GLI1, ZIC2
40lung developmentGO:0303248.6GLI1, SHH, DHCR7, GLI2
41positive regulation of transcription from RNA polymerase II promoterGO:0459448.3SIX3, SHH, GLI2, GLI1, CDON
42smoothened signaling pathwayGO:0072248.2GLI1, SHH, PTCH1, GLI2, CDON

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

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Sources for Holoprosencephaly

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
29IUPHAR
30KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
57SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet