MCID: HLP001
MIFTS: 62

Holoprosencephaly malady

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

Aliases & Classifications for Holoprosencephaly

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Sources:
32LifeMap Discovery®, 10Disease Ontology, 21GeneReviews, 45NIH Rare Diseases, 22GeneTests, 46NINDS, 47Novoseek, 12DISEASES, 51Orphanet, 24GTR, 36MeSH, 29ICD9CM, 65UMLS, 42NCIt, 59SNOMED-CT, 66UMLS via Orphanet, 28ICD10 via Orphanet, 37MESH via Orphanet, 27ICD10
See all sources

Aliases & Descriptions for Holoprosencephaly:

Name: Holoprosencephaly 32 10 21 45 22 46 47 12 51 36
Holoprosencephaly Sequence 10 24
 
Hpe 45 51


Classifications:



Characteristics (Orphanet epidemiological data):

51
holoprosencephaly:
Inheritance: Multigenic/multifactorial,Not applicable; Prevalence: 1-5/10000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: any age


External Ids:

Disease Ontology10 DOID:4621
ICD9CM29 742.2
NCIt42 C74988
MeSH36 D016142
Orphanet51 2162
SNOMED-CT59 44519006, 30915001
UMLS via Orphanet66 C0079541
ICD10 via Orphanet28 Q04.2
MESH via Orphanet37 D016142
ICD1027 Q04.2

Summaries for Holoprosencephaly

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NIH Rare Diseases:45 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: 8/25/2015

MalaCards based summary: Holoprosencephaly, also known as holoprosencephaly sequence, is related to alobar holoprosencephaly and agnathia-otocephaly complex, and has symptoms including holoprosencephaly, abnormal facial shape and single median maxillary incisor. An important gene associated with Holoprosencephaly is ZIC2 (Zic Family Member 2), and among its related pathways are Glypican 3 network and Hedgehog Pathway. Affiliated tissues include brain, eye and lung, and related mouse phenotypes are hearing/vestibular/ear and normal.

Disease Ontology:10 A congenital nervous system abnormality characterized by failed or incomplete separation of the forebrain early in gestation; it is accompanied by a spectrum of characteristic craniofacial anomalies.

NINDS:46 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:68 Holoprosencephaly (HPE, once known as arhinencephaly) is a cephalic disorder in which the prosencephalon... more...

GeneReviews summary for hpe-overview

Related Diseases for Holoprosencephaly

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Diseases in the Holoprosencephaly family:

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

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

(show top 50)    (show all 209)
idRelated DiseaseScoreTop Affiliating Genes
1alobar holoprosencephaly31.2CDON, FGF8, GLI2, NODAL, PTCH1, SHH
2agnathia-otocephaly complex30.9FGF8, GLI2, NODAL, PRRX1, SHH
3single median maxillary central incisor30.7SHH, SIX3, TGIF1
4semilobar holoprosencephaly10.7
5lobar holoprosencephaly10.7
6nonsyndromic holoprosencephaly10.5
7cleft lip10.4
8holoprosencephaly 1110.4
9familial schizencephaly, six3-related10.4SHH, SIX3
10holoprosencephaly-910.4
11hartsfield syndrome10.4
12polydactyly, preaxial type ii10.4LSS, SHH
13acheiropody10.4LSS, SHH
14holzgreve syndrome10.4GLI2, PTCH1, SIX3
15calloso-genital dysplasia10.3GLI2, PTCH1
16syndactyly, type iv10.3LSS, SHH
17inherited blood coagulation disease10.3GLI2, PTCH1, SHH
18cerebritis10.3
19basal cell nevus syndrome10.3GLI2, PTCH1, SHH
20laurin-sandrow syndrome10.3LSS, SHH
21acute dacryocystitis10.3NODAL, SIX3, ZIC2
22polydactyly10.3
23genoa syndrome10.3
24holoprosencephaly caudal dysgenesis10.3
25triploidy10.3
26microform holoprosencephaly10.3
27paranoid schizophrenia10.3GLI2, PTCH1
28tryptophan hydroxylase deficiency10.3MNX1, SHH
29exercise induced anaphylaxis10.3HPE6, TGIF1
30holoprosencephaly-310.3
31holoprosencephaly-710.3
32microcephaly10.3
33microcephaly, holoprosencephaly, and intrauterine growth retardation10.3
34morse-rawnsley-sargent syndrome10.3
35septopreoptic holoprosencephaly10.3
36mansonelliasis10.3MNX1, NODAL
37brachydactyly, type a110.3PTCH1, SHH
38esophageal diverticulosis10.2CDON, FGFR1
39caudal regression syndrome10.2
40holoprosencephaly-210.2
41holoprosencephaly-510.2
42holoprosencephaly-410.2
43microphthalmia10.2
44diabetes insipidus10.2
45iniencephaly10.2
46midline interhemispheric variant of holoprosencephaly10.2
47congenital structural myopathy10.2CDON, GLI2, SHH, SIX3, TGIF1, ZIC2
48ideomotor apraxia10.2NODAL, SIX3
49schizencephaly10.2
50smith-lemli-opitz syndrome10.2

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to holoprosencephaly

Symptoms for Holoprosencephaly

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Symptoms:

 51 (show all 90)
  • facial dysmorphism
  • anomalies of mouth, lip and philtrum
  • lateral cleft lip/gingival cleft/paramedian nasal cleft
  • cleft lip and palate
  • solitary median incisor
  • structural anomalies of the nervous system
  • holoprosencephaly/arhinencephaly/unique lateral ventricle
  • autosomal dominant inheritance
  • stillbirth/neonatal death
  • microcephaly
  • hypotelorism
  • anophthalmos/anophthalmia/microphthalmos/microphthalmia
  • cyclopia
  • coloboma of iris
  • flattened nose
  • choanal atresia
  • anosmia/cacosmia/hypogeusia/hyposmia/olfactory bulb hypoplasia
  • anodontia/oligodontia/hypodontia
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • diabetes mellitus
  • hypoglycemia
  • corpus callosum/septum pellucidum total/partial agenesis
  • dystonia/torticollis/writer's cramp/blepharospasms
  • hypotonia
  • hypertonia/spasticity/rigidity/stiffness
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • muscle weakness/flaccidity
  • skull/cranial anomalies
  • macrocephaly/macrocrania/megalocephaly/megacephaly
  • brachycephaly/flat occiput
  • frontal bossing/prominent forehead
  • hypertelorism
  • upslanted palpebral fissures/mongoloid slanting palpebral fissures
  • deepset eyes/enophthalmos
  • flat cheek bones/malar hypoplasia
  • retinoschisis/retinal/chorioretinal coloboma
  • retinopathy
  • optic nerve anomaly/optic atrophy/anomaly of the papilla
  • thick/bushy eyebrows
  • synophris/synophrys
  • high arched eyebrows
  • ptosis
  • blepharophimosis/short palpebral fissures
  • epicanthic folds
  • nasal atrophy/hypoplasia/arhinia/rudimentary nose
  • single nare/abouphalia
  • anteverted nares/nostrils
  • short columella/depressed nasal tip
  • philtrum flat/large/featureless/absent cupidon bows
  • external ear anomalies
  • antihelix anomaly
  • tragus abnormal/absent
  • branchial archs anomalies
  • short neck
  • scoliosis
  • abnormal vertebral size/shape
  • omphalocele/exomphalos
  • short hand/brachydactyly
  • upper limb polydactyly/hexadactyly
  • talipes-varus/metatarsal varus
  • intestinal atresia/stenosis/absence/agenesis/hypoplasia (excludes duodenum)
  • constipation
  • asplenia/polysplenia/spleen lobulation/accessory spleen
  • hypoplastic lungs/pulmonary hypoplasia/agenesis
  • diaphragmatic hernia/defect/agenesis
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • pulmonary valve atresia/stenosis/narrowing
  • hypoplastic aorta/coarctation/stenosis/anomaly/aortic arch interruption
  • tetralogy of fallot/trilogy of fallot
  • ventricular septal defect/interventricular communication
  • cardiac rhythm disorder/arrhythmia
  • bladder and ureter anomalies
  • proteinuria
  • micropenis/small penis/agenesis
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • hypothalamic-hypophyseal axis functional anomalies/hypopituitarism
  • diabetes insipidus
  • neural tube defect
  • encephalocele/exencephaly
  • hydrocephaly
  • dandy-walker anomaly
  • agyria/micro/pachy/macrogyria/lissencephaly/gyration/neuronal migration defect
  • cerebellum/cerebellar vermis anomaly/agenesis/hypoplasia
  • motor deficit/trouble
  • chorea/athetosis/choreoathetosis/choreic syndrome
  • hyperextensible joints/articular hyperlaxity
  • hypernatremia
  • total/partial trisomy/duplication
  • failure to thrive/difficulties for feeding in infancy/growth delay

HPO human phenotypes related to Holoprosencephaly:

(show all 86)
id Description Frequency HPO Source Accession
1 holoprosencephaly hallmark (90%) HP:0001360
2 abnormal facial shape hallmark (90%) HP:0001999
3 single median maxillary incisor hallmark (90%) HP:0006315
4 non-midline cleft lip hallmark (90%) HP:0100335
5 microcephaly typical (50%) HP:0000252
6 choanal atresia typical (50%) HP:0000453
7 depressed nasal ridge typical (50%) HP:0000457
8 hypotelorism typical (50%) HP:0000601
9 iris coloboma typical (50%) HP:0000612
10 diabetes mellitus typical (50%) HP:0000819
11 seizures typical (50%) HP:0001250
12 muscular hypotonia typical (50%) HP:0001252
13 hypertonia typical (50%) HP:0001276
14 muscle weakness typical (50%) HP:0001324
15 hypoglycemia typical (50%) HP:0001943
16 abnormality of the sense of smell typical (50%) HP:0004408
17 aplasia/hypoplasia of the corpus callosum typical (50%) HP:0007370
18 aplasia/hypoplasia affecting the eye typical (50%) HP:0008056
19 reduced number of teeth typical (50%) HP:0009804
20 cyclopia typical (50%) HP:0009914
21 cognitive impairment typical (50%) HP:0100543
22 cryptorchidism occasional (7.5%) HP:0000028
23 proteinuria occasional (7.5%) HP:0000093
24 hydrocephalus occasional (7.5%) HP:0000238
25 macrocephaly occasional (7.5%) HP:0000256
26 epicanthus occasional (7.5%) HP:0000286
27 abnormality of the philtrum occasional (7.5%) HP:0000288
28 hypertelorism occasional (7.5%) HP:0000316
29 anteverted nares occasional (7.5%) HP:0000463
30 short neck occasional (7.5%) HP:0000470
31 retinopathy occasional (7.5%) HP:0000488
32 deeply set eye occasional (7.5%) HP:0000490
33 ptosis occasional (7.5%) HP:0000508
34 chorioretinal coloboma occasional (7.5%) HP:0000567
35 thick eyebrow occasional (7.5%) HP:0000574
36 blepharophimosis occasional (7.5%) HP:0000581
37 upslanted palpebral fissure occasional (7.5%) HP:0000582
38 optic atrophy occasional (7.5%) HP:0000648
39 synophrys occasional (7.5%) HP:0000664
40 congenital diaphragmatic hernia occasional (7.5%) HP:0000776
41 anterior hypopituitarism occasional (7.5%) HP:0000830
42 diabetes insipidus occasional (7.5%) HP:0000873
43 brachydactyly syndrome occasional (7.5%) HP:0001156
44 hand polydactyly occasional (7.5%) HP:0001161
45 dandy-walker malformation occasional (7.5%) HP:0001305
46 joint hypermobility occasional (7.5%) HP:0001382
47 omphalocele occasional (7.5%) HP:0001539
48 ventricular septal defect occasional (7.5%) HP:0001629
49 tetralogy of fallot occasional (7.5%) HP:0001636
50 abnormality of the pulmonary valve occasional (7.5%) HP:0001641
51 abnormality of the aorta occasional (7.5%) HP:0001679
52 abnormality of the spleen occasional (7.5%) HP:0001743
53 talipes occasional (7.5%) HP:0001883
54 frontal bossing occasional (7.5%) HP:0002007
55 constipation occasional (7.5%) HP:0002019
56 chorea occasional (7.5%) HP:0002072
57 encephalocele occasional (7.5%) HP:0002084
58 respiratory insufficiency occasional (7.5%) HP:0002093
59 abnormality of neuronal migration occasional (7.5%) HP:0002269
60 highly arched eyebrow occasional (7.5%) HP:0002553
61 scoliosis occasional (7.5%) HP:0002650
62 abnormality of chromosome segregation occasional (7.5%) HP:0002916
63 hypernatremia occasional (7.5%) HP:0003228
64 abnormal form of the vertebral bodies occasional (7.5%) HP:0003312
65 aplasia/hypoplasia of the lungs occasional (7.5%) HP:0006703
66 aplasia/hypoplasia of the cerebellum occasional (7.5%) HP:0007360
67 external ear malformation occasional (7.5%) HP:0008572
68 hypoplasia of penis occasional (7.5%) HP:0008736
69 abnormality of the antihelix occasional (7.5%) HP:0009738
70 branchial anomaly occasional (7.5%) HP:0009794
71 abnormality of the tragus occasional (7.5%) HP:0009912
72 aplasia/hypoplasia involving the nose occasional (7.5%) HP:0009924
73 spinal dysraphism occasional (7.5%) HP:0010301
74 hypoplasia of the zygomatic bone occasional (7.5%) HP:0010669
75 arrhythmia occasional (7.5%) HP:0011675
76 absent nares occasional (7.5%) HP:0100596
77 autosomal recessive inheritance HP:0000007
78 micropenis HP:0000054
79 hypotelorism HP:0000601
80 adrenal hypoplasia HP:0000835
81 seizures HP:0001250
82 hypoglycemia HP:0001943
83 facial cleft HP:0002006
84 alobar holoprosencephaly HP:0006988
85 median cleft lip and palate HP:0008501
86 cyclopia HP:0009914

Drugs & Therapeutics for Holoprosencephaly

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Study of the Experiences and Needs of Parents Continuing a Pregnancy Following a Prenatal Diagnosis of HolopresencephalyCompletedNCT00005016
2Genetic Analysis of Left-Right Axis FormationsCompletedNCT00341133
3Clinical and Genetic Studies on HoloprosencephalyRecruitingNCT00088426
4Genetic Analysis of Brain DisordersRecruitingNCT00341978
5A Study of the Genetic Analysis of Brain DisordersRecruitingNCT00645645

Search NIH Clinical Center for Holoprosencephaly


Cochrane evidence based reviews: Holoprosencephaly

Genetic Tests for Holoprosencephaly

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Genetic tests related to Holoprosencephaly:

id Genetic test Affiliating Genes
1 Holoprosencephaly22 ZIC2
2 Holoprosencephaly Sequence24

Anatomical Context for Holoprosencephaly

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MalaCards organs/tissues related to Holoprosencephaly:

33
Brain, Eye, Lung, Spleen, Bone, Cerebellum, Testes

LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Holoprosencephaly:
id TissueAnatomical CompartmentCell Relevance
1 Primitive StreakPrimitive Streak  Affected by disease

Animal Models for Holoprosencephaly or affiliated genes

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MGI Mouse Phenotypes related to Holoprosencephaly:

38 (show all 16)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:000537710.0FGF8, FGFR1, GLI2, LRP2, PRRX1, SHH
2MP:00028739.9FGF8, FGFR1, GLI2, MNX1, NODAL, PTCH1
3MP:00053719.7CDON, DHCR7, FGF8, FGFR1, GLI2, PRRX1
4MP:00053699.7DHCR7, FGF8, FGFR1, GLI2, MNX1, NODAL
5MP:00053849.6CDON, FGF8, FGFR1, GLI2, LRP2, MNX1
6MP:00053859.4CDON, DHCR7, FGF8, FGFR1, MNX1, NODAL
7MP:00053919.4CDON, FGF8, FGFR1, GLI2, LRP2, NODAL
8MP:00053819.3CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2
9MP:00053829.3CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2
10MP:00053889.3CDON, DHCR7, GLI2, LRP2, MNX1, NODAL
11MP:00053809.3CDON, FGF8, FGFR1, GLI2, LRP2, NODAL
12MP:00053909.2CDON, FGF8, FGFR1, GLI2, LRP2, MNX1
13MP:00053789.0CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2
14MP:00107688.8CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2
15MP:00036318.6CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2
16MP:00053868.6CDON, DHCR7, FGF8, FGFR1, GLI2, LRP2

Publications for Holoprosencephaly

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Articles related to Holoprosencephaly:

(show top 50)    (show all 595)
idTitleAuthorsYear
1
Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice. (25468951)
2015
2
Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism. (24706429)
2014
3
Cyclopia, proboscis and alobar holoprosencephaly representative for trisomy 13. (25365860)
2014
4
Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly and congenital heart defects. (24091065)
2014
5
STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly. (25218063)
2014
6
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. (23812909)
2013
7
Holoprosencephaly: report of four cases and genotype-phenotype correlations. (23640411)
2013
8
Thick corpus callosum: a clue to the diagnosis of fetal septopreoptic holoprosencephaly? (22006531)
2012
9
Congenital partial arhinia: a rare malformation of the nose coexisting with holoprosencephaly. (23692731)
2012
10
Duplication of the ZIC2 gene is not associated with holoprosencephaly. (22105922)
2012
11
Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis. (21204232)
2011
12
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
13
Two cases of single-stage lip and nostril reconstruction in holoprosencephaly. (21470822)
2011
14
Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation. (20104607)
2010
15
Clinical image. Middle interhemispheric variant of holoprosencephaly. (19997726)
2010
16
Moebius syndrome and holoprosencephaly following exposure to misoprostol. (20933185)
2010
17
Sonographic diagnosis of brain malformations, part 2: holoprosencephaly - hydranencephaly - agenesis of septum pellucidum - schizencephaly - septo-optical dysplasia. (21117007)
2010
18
Lobar holoprosencephaly with a median cleft: case report. (19929095)
2009
19
Holoprosencephaly spectrum, ano/microphthalmia, and first branchial arch defects: evidence for a new disorder. (18049080)
2008
20
Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. (18694563)
2008
21
Prenatal MRI image of a fetus with semilobar holoprosencephaly. (21654965)
2008
22
Holoprosencephaly: an antenatally-diagnosed case series and subject review. (18695774)
2008
23
Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation. (18617531)
2008
24
Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly. (18338389)
2008
25
A triploid fetus further expands etiological heterogeneity in holoprosencephaly-diencephalic hamartoblastoma. (17497722)
2007
26
A mechanism for mutational inactivation of the homeodomain protein TGIF in holoprosencephaly. (17158784)
2007
27
Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly. (16503393)
2006
28
Links between abnormal brain structure and cognition in holoprosencephaly. (17138007)
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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Clinvar genetic disease variations for Holoprosencephaly:

5 (show all 60)
id Gene Variation Type Significance SNP ID Assembly Location
1GLI2GLI2, 1-BP DEL, NT2274deletionPathogenic
2GLI2NM_005270.4(GLI2): c.1323G> A (p.Trp441Ter)single nucleotide variantPathogenicrs121917707GRCh37Chr 2, 121732640: 121732640
3GLI2NM_005270.4(GLI2): c.1435C> G (p.Arg479Gly)single nucleotide variantPathogenicrs121917708GRCh37Chr 2, 121736076: 121736076
4ZIC2NM_007129.3(ZIC2): c.1245T> G (p.His415Gln)single nucleotide variantLikely pathogenicrs794729641GRCh37Chr 13, 100637582: 100637582
5ZIC2ZIC2, 7-BP DEL, NT392deletionPathogenic
6CDONNM_016952.4(CDON): c.2065C> G (p.Pro689Ala)single nucleotide variantPathogenicrs387906995GRCh37Chr 11, 125871707: 125871707
7CDONNM_016952.4(CDON): c.2339T> A (p.Val780Glu)single nucleotide variantPathogenicrs387906996GRCh37Chr 11, 125867125: 125867125
8CDONNM_016952.4(CDON): c.2368A> G (p.Thr790Ala)single nucleotide variantPathogenicrs387906997GRCh37Chr 11, 125864942: 125864942
9CDONNM_016952.4(CDON): c.2818A> C (p.Ser940Arg)single nucleotide variantPathogenicrs369673018GRCh37Chr 11, 125853944: 125853944
10GLI2NM_005270.4(GLI2): c.864_865delCC (p.His289Profs)deletionPathogenicrs398122882GRCh37Chr 2, 121727987: 121727988
11GLI2NM_005270.4(GLI2): c.1885G> A (p.Glu629Lys)single nucleotide variantPathogenicrs387907277GRCh37Chr 2, 121742248: 121742248
12SIX3NM_005413.3(SIX3): c.676C> G (p.Leu226Val)single nucleotide variantPathogenicrs121917878GRCh37Chr 2, 45169919: 45169919
13SIX3NM_005413.3(SIX3): c.770G> C (p.Arg257Pro)single nucleotide variantPathogenicrs121917879GRCh37Chr 2, 45170013: 45170013
14SIX3NM_005413.3(SIX3): c.749T> C (p.Val250Ala)single nucleotide variantPathogenicrs121917880GRCh37Chr 2, 45169992: 45169992
15SIX3SIX3, 2-BP INS, 557GGinsertionPathogenic
16SIX3SIX3, 2-BP INS, 406GCinsertionPathogenic
17SIX3NM_005413.3(SIX3): c.206G> A (p.Gly69Asp)single nucleotide variantPathogenicrs121917881GRCh37Chr 2, 45169449: 45169449
18SIX3NM_005413.3(SIX3): c.339G> T (p.Trp113Cys)single nucleotide variantPathogenicrs137853021GRCh37Chr 2, 45169582: 45169582
19ZIC2NM_007129.3(ZIC2): c.936delG (p.Lys312Asnfs)deletionPathogenicrs397515499GRCh37Chr 13, 100635254: 100635254
201 bp del G 7deletionPathogenic
21ZIC2NM_007129.3(ZIC2): c.1091_1092delAG (p.Gln364Leufs)deletionPathogenicrs397515500GRCh37Chr 13, 100637215: 100637216
22SIX3NM_005413.3(SIX3): c.696_705delCCCCAGCAAG (p.Asn232Lysfs)deletionPathogenicrs397515502GRCh37Chr 2, 45169939: 45169948
23NM_000193.2: c.1308C> Tsingle nucleotide variantPathogenic
24SHHNM_000193.3(SHH): c.1210_1224delGGGGACCGCGGGGGC (p.Asp405_Gly409del)deletionPathogenicrs587778786GRCh37Chr 7, 155595759: 155595773
25SHHNM_000193.3(SHH): c.9_10insGCTG (p.Leu4Alafs)insertionPathogenicrs587778788GRCh37Chr 7, 155604807: 155604808
26SHHNM_000193.3(SHH): c.38_45delTCTCCTCG (p.Val13Alafs)deletionPathogenicrs587778789GRCh37Chr 7, 155604772: 155604779
27SHHNM_000193.3(SHH): c.300G> C (p.Gln100His)single nucleotide variantPathogenicrs587778792GRCh37Chr 7, 155604517: 155604517
28SHHNM_000193.3(SHH): c.474C> G (p.Tyr158Ter)single nucleotide variantPathogenicrs146990376GRCh37Chr 7, 155599078: 155599078
29SHHNM_000193.3(SHH): c.562G> C (p.Glu188Gln)single nucleotide variantPathogenicrs587778799GRCh37Chr 7, 155598990: 155598990
30SHHNM_000193.3(SHH): c.625C> T (p.Gln209Ter)single nucleotide variantPathogenicrs587778803GRCh37Chr 7, 155596358: 155596358
31SHHNM_000193.3(SHH): c.664G> A (p.Asp222Asn)single nucleotide variantPathogenicrs587778805GRCh37Chr 7, 155596319: 155596319
32SHHNM_000193.3(SHH): c.708C> A (p.Ser236Arg)single nucleotide variantPathogenicrs587778806GRCh37Chr 7, 155596275: 155596275
33ZIC2NM_007129.3(ZIC2): c.177_178ins56 (p.?)insertionPathogenicGRCh37Chr 13, 100634495: 100634496
34ZIC2NM_007129.3(ZIC2): c.1318dupC (p.Leu440Profs)duplicationPathogenicrs397515364GRCh37Chr 13, 100637655: 100637655
35ZIC2NM_007129.3(ZIC2): c.1366_1368(15_45)NT expansionPathogenicGRCh37Chr 13, 100637703: 100637705
36ZIC2NM_007129.3(ZIC2): c.1040_1046delCCGAGAA (p.Glu348Serfs)deletionPathogenicrs397515365GRCh37Chr 13, 100635358: 100635364
37ZIC2ZIC2, 2-BP DEL, 180ACdeletionPathogenic
38TGIF1NM_170695.3(TGIF1): c.470C> G (p.Ser157Cys)single nucleotide variantPathogenicrs121909066GRCh37Chr 18, 3456418: 3456418
39TGIF1NM_170695.3(TGIF1): c.575C> G (p.Pro192Arg)single nucleotide variantPathogenicrs121909067GRCh37Chr 18, 3456523: 3456523
40TGIF1NM_170695.3(TGIF1): c.838A> G (p.Thr280Ala)single nucleotide variantPathogenicrs121909068GRCh37Chr 18, 3457570: 3457570
41TGIF1NM_170695.3(TGIF1): c.872C> T (p.Ser291Phe)single nucleotide variantPathogenicrs121909069GRCh37Chr 18, 3457604: 3457604
42TGIF1NM_170695.3(TGIF1): c.177C> G (p.Tyr59Ter)single nucleotide variantPathogenicrs121909070GRCh37Chr 18, 3452154: 3452154
43TGIF1NM_170695.3(TGIF1): c.707A> T (p.Gln236Leu)single nucleotide variantPathogenicrs28939693GRCh37Chr 18, 3457439: 3457439
44PTCH1NM_000264.3(PTCH1): c.1177G> A (p.Ala393Thr)single nucleotide variantPathogenicrs199476091GRCh37Chr 9, 98241320: 98241320
45PTCH1NM_000264.3(PTCH1): c.2723T> G (p.Val908Gly)single nucleotide variantPathogenicrs199476093GRCh37Chr 9, 98222046: 98222046
46SHHNM_000193.3(SHH): c.91G> A (p.Gly31Arg)single nucleotide variantPathogenicrs28936675GRCh37Chr 7, 155604726: 155604726
47SHHNM_000193.3(SHH): c.298C> T (p.Gln100Ter)single nucleotide variantPathogenicrs104894044GRCh37Chr 7, 155604519: 155604519
48SHHNM_000193.3(SHH): c.313A> T (p.Lys105Ter)single nucleotide variantPathogenicrs104894045GRCh37Chr 7, 155599239: 155599239
49SHHNM_000193.3(SHH): c.349T> G (p.Trp117Gly)single nucleotide variantPathogenicrs104894040GRCh37Chr 7, 155599203: 155599203
50SHHNM_000193.3(SHH): c.349T> C (p.Trp117Arg)single nucleotide variantPathogenicrs104894040GRCh37Chr 7, 155599203: 155599203
51SHHNM_000193.3(SHH): c.671T> A (p.Val224Glu)single nucleotide variantPathogenicrs104894042GRCh37Chr 7, 155596312: 155596312
52SHHNM_000193.3(SHH): c.676G> A (p.Ala226Thr)single nucleotide variantPathogenicrs104894043GRCh37Chr 7, 155596307: 155596307
53SHHNM_000193.3(SHH): c.788_808del21 (p.Arg263_Ala269del)deletionPathogenicrs397515375GRCh37Chr 7, 155596175: 155596195
54SHHNM_000193.3(SHH): c.850G> T (p.Glu284Ter)single nucleotide variantPathogenicrs104894046GRCh37Chr 7, 155596133: 155596133
55SHHNM_000193.3(SHH): c.1147G> A (p.Ala383Thr)single nucleotide variantPathogenicrs137853341GRCh37Chr 7, 155595836: 155595836
56SHHNM_000193.3(SHH): c.1270C> G (p.Pro424Ala)single nucleotide variantPathogenicrs104894048GRCh37Chr 7, 155595713: 155595713
57SHHNM_000193.3(SHH): c.1132_1140delGCGCCCTTC (p.Ala378_Phe380del)deletionPathogenicrs397515376GRCh37Chr 7, 155595843: 155595851
58SHHNM_000193.3(SHH): c.263A> T (p.Asp88Val)single nucleotide variantPathogenicrs104894050GRCh37Chr 7, 155604554: 155604554
59SHHNM_000193.3(SHH): c.766G> T (p.Glu256Ter)single nucleotide variantPathogenicrs104894051GRCh37Chr 7, 155596217: 155596217
60SHHNM_000193.3(SHH): c.345C> A (p.Asn115Lys)single nucleotide variantPathogenicrs267607047GRCh37Chr 7, 155599207: 155599207

Expression for genes affiliated with Holoprosencephaly

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Search GEO for disease gene expression data for Holoprosencephaly.

Pathways for genes affiliated with Holoprosencephaly

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GO Terms for genes affiliated with Holoprosencephaly

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Biological processes related to Holoprosencephaly according to GeneCards Suite gene sharing:

(show top 50)    (show all 59)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of skeletal muscle tissue developmentGO:004864311.0CDON, SHH
2ventral midline developmentGO:000741811.0GLI2, SHH
3smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferationGO:002193811.0GLI2, SHH
4hindgut morphogenesisGO:000744211.0GLI2, SHH
5smoothened signaling pathway involved in dorsal/ventral neural tube patterningGO:006083110.9GLI2, PTCH1
6positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetryGO:190022410.9NODAL, ZIC2
7formation of anatomical boundaryGO:004885910.9NODAL, SHH
8embryonic morphogenesisGO:004859810.9CDON, SHH
9forebrain dorsal/ventral pattern formationGO:002179810.9FGF8, SIX3
10positive regulation of T cell differentiation in thymusGO:003308910.9GLI2, SHH
11somite developmentGO:006105310.9PTCH1, SHH
12pharyngeal system developmentGO:006003710.9FGF8, PTCH1
13organ inductionGO:000175910.9FGF8, FGFR1
14regulation of gastrulationGO:001047010.9NODAL, TGIF1
15nodal signaling pathwayGO:003809210.9NODAL, TGIF1
16telencephalon regionalizationGO:002197810.9SHH, SIX3
17lung-associated mesenchyme developmentGO:006048410.9FGFR1, SHH
18anatomical structure developmentGO:004885610.9GLI2, SHH
19cell proliferation in forebrainGO:002184610.9FGF8, SIX3
20striated muscle cell differentiationGO:005114610.8CDON, SHH
21central nervous system neuron developmentGO:002195410.8FGF8, FGFR1
22smoothened signaling pathwayGO:000722410.7GLI2, PTCH1, SHH
23positive regulation of mesenchymal cell proliferationGO:000205310.7FGFR1, PRRX1, SHH
24regulation of smoothened signaling pathwayGO:000858910.7GLI2, PTCH1, ZIC1
25mammary gland duct morphogenesisGO:006060310.7GLI2, PTCH1
26dorsal/ventral neural tube patterningGO:002190410.7GLI2, MNX1, PTCH1, SHH
27anatomical structure formation involved in morphogenesisGO:004864610.7GLI2, NODAL, SHH
28spinal cord motor neuron differentiationGO:002152210.7GLI2, PTCH1, SHH
29branching involved in salivary gland morphogenesisGO:006044510.7FGF8, FGFR1, SHH
30dorsal/ventral pattern formationGO:000995310.7GLI2, PTCH1, SHH, TGIF1
31cell fate commitmentGO:004516510.7FGF8, NODAL, SHH
32canonical Wnt signaling pathwayGO:006007010.6FGF8, LRP2, SHH
33heart loopingGO:000194710.6FGF8, NODAL, SHH
34generation of neuronsGO:004869910.6FGF8, FGFR1
35branching involved in ureteric bud morphogenesisGO:000165810.6FGF8, PTCH1, SHH
36anterior/posterior pattern specificationGO:000995210.6CDON, NODAL, SHH
37pattern specification processGO:000738910.6GLI2, PTCH1, SHH, ZIC1
38neural tube closureGO:000184310.6PTCH1, TGIF1, ZIC2
39embryonic limb morphogenesisGO:003032610.4FGFR1, PRRX1, PTCH1, SHH
40in utero embryonic developmentGO:000170110.4FGFR1, GLI2, NODAL, PTCH1
41regulation of cell proliferationGO:004212710.2DHCR7, FGFR1, PTCH1, SHH, SIX3
42positive regulation of cell proliferationGO:000828410.1FGF8, FGFR1, GLI2, NODAL, SHH
43inner ear morphogenesisGO:004247210.1FGF8, FGFR1, PRRX1, ZIC1
44heart developmentGO:000750710.1FGF8, GLI2, NODAL, SHH
45lung developmentGO:003032410.1DHCR7, FGF8, FGFR1, GLI2, NODAL, SHH
46determination of left/right symmetryGO:000736810.0FGF8, NODAL, SHH, TGIF1
47positive regulation of neuron differentiationGO:00456669.9CDON, FGFR1, GLI2, TGIF1
48brain developmentGO:00074209.8FGFR1, NODAL, PTCH1, SIX3, ZIC1, ZIC2
49positive regulation of transcription from RNA polymerase II promoterGO:00459449.6CDON, GLI2, NODAL, PRRX1, SHH, SIX3
50negative regulation of transcription from RNA polymerase II promoterGO:00001229.3FGFR1, GLI2, NODAL, PRRX1, PTCH1, SHH

Molecular functions related to Holoprosencephaly according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1morphogen activityGO:001601510.2NODAL, SHH
2patched bindingGO:000511310.0PTCH1, SHH

Sources for Holoprosencephaly

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet