HPE
MCID: HLP001
MIFTS: 61

Holoprosencephaly (HPE) malady

Summaries for Holoprosencephaly

Sources:
43NIH Rare Diseases, 44NINDS, 64Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
See all sources

Fully expand this MalaCard

Export 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 polydactyly. 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, kidney and cortex, and related mouse phenotypes are respiratory system and limbs/digits/tail.

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

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

GeneReviews summary for hpe-overview

Aliases & Classifications for Holoprosencephaly

Sources:
19GeneReviews, 8Disease Ontology, 43NIH Rare Diseases, 20GeneTests, 44NINDS, 10DISEASES, 45Novoseek, 22GTR, 61UMLS, 47OMIM, 57SNOMED-CT, 35MeSH, 40NCIt
See all sources

Aliases & Descriptions:

holoprosencephaly 8 19 43 20 44 10 45
holoprosencephaly sequence 8 22
hirschsprung disease 1 61
aganglionic megacolon 19
hscr 19
hpe 43


External Ids:

Disease Ontology8 DOID:4621
SNOMED-CT57 30915001, 44519006
MeSH35 D016142
NCIt40 C74988

Related Diseases for Holoprosencephaly

Sources:
17GeneCards, 18GeneDecks
See all sources

Diseases in the Holoprosencephaly family:

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 172)
idRelated DiseaseScoreTop Affiliating Genes
1semilobar holoprosencephaly30.9SHH
2polydactyly30.3SHH, GLI2, GLI1, FGF8, PTCH1, DHCR7
3microcephaly30.2TGIF1, SHH
4microphthalmia30.2SIX3
5coloboma30.1SIX3
6smith-lemli-opitz syndrome30.1SHH, DHCR7
7moyamoya disease29.7TGIF1
8spina bifida29.7ZIC2, ZIC1
9alobar holoprosencephaly10.7
10hirschsprung's disease10.7
11lobar holoprosencephaly10.6
12holoprosencephaly-110.5
13nonsyndromic holoprosencephaly10.5
14holoprosencephaly-710.3
15holoprosencephaly-210.3
16genoa syndrome10.2
17hartsfield syndrome10.2
18hirschsprung disease type 310.2
19hirschsprung disease type 210.2
20hirschsprung disease 410.2
21renal hypoplasia10.2
22cleft palate10.2
23n syndrome10.2
24triploidy10.2
25holoprosencephaly-310.2
26diabetes insipidus10.2
27steinfeld syndrome10.2
28central hypoventilation syndrome, congenital, with or without hirschsprung disease10.2
29caudal regression syndrome10.1
30holoprosencephaly caudal dysgenesis10.1
31microcephaly, holoprosencephaly, and intrauterine growth retardation10.1
32single median maxillary central incisor10.1
33holoprosencephaly 1110.1
34holoprosencephaly - postaxial polydactyly10.1
35septopreoptic holoprosencephaly10.1
36ret-related hirschsprung disease10.1
37nrtn-related hirschsprung disease10.1
38gdnf-related hirschsprung disease10.1
39ednrb-related hirschsprung disease10.1
40edn3-related hirschsprung disease10.1
41ece1-related hirschsprung disease10.1
42aicardi syndrome10.1
43micro syndrome10.1
44corpus callosum agenesis10.1
45dysgnathia complex10.1
46encephalocele10.1
47septo-optic dysplasia10.1
48schizencephaly10.1
49iniencephaly10.1
50hpe6-related holoprosencephaly10.1

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to holoprosencephaly

Clinical Features for Holoprosencephaly

Sources:
47OMIM
See all sources

Clinical features from OMIM:

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

Drugs & Therapeutics for Holoprosencephaly

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
See all sources

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

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

Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Holoprosencephaly:

33
Brain, Kidney, Cortex, Cerebellum, Retina, Heart, Pancreas, T cells, B lymphoblasts, B cells, Fetal brain, Temporal lobe, Occipital lobe, Thalamus, Pituitary

Animal Models for Holoprosencephaly or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
See all sources

Publications for Holoprosencephaly

Sources:
51PubMed
See all sources

Articles related to Holoprosencephaly:

(show top 50)    (show all 554)
idTitleAuthorsYear
1
Alobar holoprosencephaly with cyclopia - autopsy-based observations from one medical center. (23791929)
2013
2
Chromosome 18p deletion syndrome presenting holoprosencephaly and premaxillary agenesis: prenatal diagnosis and aCGH characterization using uncultured amniocytes. (23850725)
2013
3
Vertically oval corneas in a child with holoprosencephaly. (22800857)
2012
4
Genetic Overlap between Holoprosencephaly and Kallmann Syndrome. (22855648)
2012
5
An acardiac twin with advanced brain development and a minor form of holoprosencephaly and intracerebral retina-like pigmented tissue: a case report and review of the literature. (21488711)
2011
6
Holoprosencephaly in hungary: birth prevalence and clinical spectrum. (21515784)
2011
7
Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly. (19398181)
2010
8
Introduction to the American Journal of Medical Genetics Part C on holoprosencephaly. (20104593)
2010
9
Solitary median maxillary central incisor syndrome and holoprosencephaly: a case report. (21070710)
2010
10
Prenatal diagnosis and molecular analysis of triploidy in a fetus with intrauterine growth restriction, relative macrocephaly and holoprosencephaly. (19797034)
2009
11
Holoprosencephaly in an 8.5-week triploidy gestation. (19357506)
2009
12
Sonic hedgehog mutations identified in holoprosencephaly patients can act in a dominant negative manner. (19057928)
2009
13
Central tegmental tract lesion in a girl with holoprosencephaly presenting with West syndrome. (18692418)
2009
14
Selective depletion of molecularly defined cortical interneurons in human holoprosencephaly with severe striatal hypoplasia. (19234067)
2009
15
Prenatal MRI findings of polycystic kidney disease associated with holoprosencephaly. (19412520)
2009
16
Prenatal visualization of cebocephaly with a prominent nose in a second-trimester fetus with alobar holoprosencephaly and trisomy 13. (18400592)
2008
17
Alobar holoprosencephaly. (19203004)
2008
18
Sonic Hedgehog deletion and distal trisomy 3p in a patient with microphthalmia and microcephaly, lacking cerebral anomalies typical of holoprosencephaly. (18762283)
2008
19
Holoprosencephaly in Ibadan, Nigeria: a report of three cases and review of literature. (18390070)
2007
20
Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association. (17230485)
2007
21
Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype. (17269127)
2007
22
Abnormal sterol metabolism in holoprosencephaly: studies in cultured lymphoblasts. (17237122)
2007
23
Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog. (17525797)
2007
24
Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly. (16503393)
2006
25
Links between abnormal brain structure and cognition in holoprosencephaly. (17138007)
2006
26
Holoprosencephaly-like phenotype: clinical and genetic perspectives. (17001669)
2006
27
SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor. (15942952)
2005
28
Seven letters to the editor reporting new findings in patients with holoprosencephaly. (15942951)
2005
29
Plastic surgery considerations for holoprosencephaly patients. (15213551)
2004
30
First-trimester sonographic diagnosis of holoprosencephaly: value of the "butterfly" sign. (15244299)
2004
31
Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. (15523651)
2004
32
The interplay of genetic and environmental factors in craniofacial morphogenesis: holoprosencephaly and the role of cholesterol. (12692399)
2003
33
Semilobar holoprosencephaly diagnosed by MRI. (12152724)
2002
34
Investigation of the epidemiology and prenatal diagnosis of holoprosencephaly in the North of England. (11349198)
2001
35
Unusually prolonged survival and childhood-onset epilepsy in a case of alobar holoprosencephaly. (10392502)
1999
36
Coexistent holoprosencephaly and Chiari II malformation. (10543640)
1999
37
Association of holoprosencephaly, ectrodactyly, cleft lip/cleft palate and hypertelorism: a possible third case. (9689997)
1998
38
Isolation of a 370 kb YAC fragment spanning a translocation breakpoint at 3p14.1 associated with holoprosencephaly. (9842993)
1998
39
Absence of the superior labial frenulum in holoprosencephaly: a new diagnostic sign. (9672532)
1998
40
Segregation analysis in nonsyndromic holoprosencephaly. (9605287)
1998
41
Palate structure in human holoprosencephaly correlates with the facial malformation and demonstrates a new palatal developmental field. (9415463)
1997
42
Midline interhemispheric fusion associated with atypical callosal dysgenesis: a mild type of holoprosencephaly. (8826753)
1996
43
Holoprosencephaly and chromosomal anomalies. (8993141)
1996
44
Anterior callosal agenesis in mild, lobar holoprosencephaly. (7567274)
1995
45
Psychosis associated with lobar holoprosencephaly. (7987790)
1994
46
Autosomal recessive alobar holoprosencephaly with cyclops in three female sibs: prenatal ultrasonographic diagnosis at 18th week. (8281281)
1993
47
Holoprosencephaly and polydactyly: a possible expression of the hydrolethalus syndrome. (2407847)
1990
48
Disorders of midline structures: holoprosencephaly, absence of corpus callosum, and Chiari malformations. (3078668)
1988
49
Aicardi syndrome with holoprosencephaly and cleft lip and palate. (3508052)
1987
50
UNIQUE ANGIOGRAPHIC AND VENTRICULOGRAPHIC PATTERN OF ALOBAR HOLOPROSENCEPHALY (ARHINENCEPHALY). (14282709)
1965

Genetic Variations for Holoprosencephaly

Expression for genes affiliated with Holoprosencephaly

Sources:
1BioGPS, 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

Sources:
38NCBI BioSystems Database, 54Reactome, 12EMD Millipore, 60Tocris Bioscience, 4Cell Signaling Technology, 30KEGG
See all sources

Compounds for genes affiliated with Holoprosencephaly

Sources:
60Tocris Bioscience, 45Novoseek, 24HMDB
See all sources

Compounds related to Holoprosencephaly according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1ay 9944 dihydrochloride6010.5SHH, GLI1, DHCR7
2cyclopamine45 6011.4SHH, GLI1, PTCH1
3sant-16010.4SHH, GLI1
420(s)-hydroxycholesterol6010.3GLI1, SHH
5zinc45 2411.2TGIF1, ZIC1, ZIC2, GLI2, GLI1, FGF8
6ciliobrevin a6010.1SHH, GLI1

GO Terms for genes affiliated with Holoprosencephaly

Sources:
16Gene Ontology
See all sources

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

  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Holoprosencephaly

3CDC
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
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet