HPE1
MCID: HLP023
MIFTS: 47

Holoprosencephaly 1 (HPE1)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Holoprosencephaly 1

MalaCards integrated aliases for Holoprosencephaly 1:

Name: Holoprosencephaly 1 57 12 29 6 15
Arhinencephaly 57 40 73
Cyclopia 57 29 55
Hpe1 57 12
Holoprosencephaly, Familial Alobar 57
Hpe, Familial; Hpec 57
Holoprosencephaly-1 13
Demyer Sequence 57
Hpe, Familial 57
Hpec 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant
isolated cases

Miscellaneous:
variable severity
genetic heterogeneity
incomplete penetrance
spectrum of malformations resulting from impaired midline cleavage of the embryonic forebrain



Classifications:



Summaries for Holoprosencephaly 1

OMIM : 57 Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain and occurs after failed or abbreviated midline cleavage of the developing brain during the third and fourth weeks of gestation. HPE occurs in up to 1 in 250 gestations, but only 1 in 8,000 live births (Lacbawan et al., 2009). Classically, 3 degrees of severity defined by the extent of brain malformation have been described. In the most severe form, 'alobar HPE,' there is a single ventricle and no interhemispheric fissure. The olfactory bulbs and tracts and the corpus callosum are typically absent. In 'semilobar HPE,' the most common type of HPE in neonates who survive, there is partial cortical separation with rudimentary cerebral hemispheres and a single ventricle. In 'lobar HPE,' the ventricles are separated, but there is incomplete frontal cortical separation (Corsello et al., 1990). An additional milder form, called 'middle interhemispheric variant' (MIHV) has also been delineated, in which the posterior frontal and parietal lobes are incompletely separated and the corpus callosum may be hypoplastic (Lacbawan et al., 2009). Finally, microforms of HPE include a single maxillary median incisor or hypotelorism without the typical brain malformations (summary by Mercier et al., 2011). Cohen (2001) discussed problems in the definition of holoprosencephaly, which can be viewed from 2 different perspectives: anatomic (fixed) and genetic (broad). When the main interest is description, the anatomic perspective is appropriate. In genetic perspective, a fixed definition of holoprosencephaly is not appropriate because the same mutational cause may result in either holoprosencephaly or some microform of holoprosencephaly. Cohen (2001) concluded that both fixed and broad definitions are equally valid and depend on context. Munke (1989) provided an extensive review of the etiology and pathogenesis of holoprosencephaly, emphasizing heterogeneity. See also schizencephaly (269160), which may be part of the phenotypic spectrum of HPE. (236100)

MalaCards based summary : Holoprosencephaly 1, also known as arhinencephaly, is related to semilobar holoprosencephaly and alobar holoprosencephaly. An important gene associated with Holoprosencephaly 1 is HPE1 (Holoprosencephaly 1, Alobar), and among its related pathways/superpathways is Signaling events mediated by the Hedgehog family. The drugs Tobramycin and Minocycline have been mentioned in the context of this disorder. Affiliated tissues include brain, olfactory bulb and parietal lobe, and related phenotypes are agenesis of corpus callosum and intellectual disability

Disease Ontology : 12 A holoprosencephaly that has material basis in variation in the chromosome region 21q22.3.

Related Diseases for Holoprosencephaly 1

Diseases in the Holoprosencephaly family:

Holoprosencephaly 3 Holoprosencephaly 4
Holoprosencephaly 2 Holoprosencephaly 1
Holoprosencephaly 6 Holoprosencephaly 8
Holoprosencephaly 5 Holoprosencephaly 7
Holoprosencephaly 9 Holoprosencephaly 11
Nonsyndromic Holoprosencephaly

Diseases related to Holoprosencephaly 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 53)
# Related Disease Score Top Affiliating Genes
1 semilobar holoprosencephaly 30.0 GAS1 SHH SIX3
2 alobar holoprosencephaly 30.0 GAS1 SHH SIX3
3 holoprosencephaly 29.5 GAS1 HPE1 LSS SHH SIX3 TRAPPC10
4 isolated arhinencephaly 12.2
5 iniencephaly 11.4
6 holoprosencephaly 9 11.1
7 perrault syndrome 1 11.1
8 xk aprosencephaly 11.1
9 patau syndrome 10.2
10 acquired schizencephaly 10.2 SHH SIX3
11 polydactyly 10.2
12 sirenomelia 10.2
13 triploidy 10.2
14 septopreoptic holoprosencephaly 10.2 GAS1 SHH SIX3
15 midline interhemispheric variant of holoprosencephaly 10.2 GAS1 SHH SIX3
16 lobar holoprosencephaly 10.1 GAS1 SHH SIX3
17 microform holoprosencephaly 10.1 GAS1 SHH SIX3
18 chromosome 18p deletion syndrome 10.1 SHH SIX3
19 ancylostomiasis 10.1 MT-CO1 SERPINA1
20 diphyllobothriasis 10.1 MT-CO1 SERPINA1
21 neural tube defects 10.1
22 neural tube defects, folate-sensitive 10.1
23 cleft lip 10.1
24 cleft lip/palate 10.1
25 mucinous cystadenofibroma 10.0 CEACAM5 SERPINA1
26 agnathia-otocephaly complex 10.0
27 brachydactyly, type a1 10.0 GAS1 SHH
28 pancreatic steatorrhea 10.0 CELA1 CELA3B
29 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 10.0 AIRE TRAPPC10
30 hydrocephalus 9.9
31 microphthalmia 9.9
32 microcephaly 9.9
33 encephalocele 9.9
34 exencephaly 9.9
35 sarcoma 9.9
36 alopecia 9.9
37 rapidly involuting congenital hemangioma 9.9
38 cytomegalovirus infection 9.9
39 mosaic trisomy 13 9.9
40 congenital cytomegalovirus 9.9
41 chromosome 3p duplication 9.9
42 situs inversus 9.9
43 gestational trophoblastic neoplasm 9.9
44 cystic lymphangioma 9.9
45 orbital cyst 9.9
46 bone resorption disease 9.9
47 myelomeningocele 9.9
48 patent ductus arteriosus 1 9.9
49 gonadal agenesis 9.9
50 opitz gbbb syndrome, type i 9.9

Graphical network of the top 20 diseases related to Holoprosencephaly 1:



Diseases related to Holoprosencephaly 1

Symptoms & Phenotypes for Holoprosencephaly 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
cerebellar hypoplasia
developmental delay
hypotonia
agenesis of the corpus callosum
more
Growth Height:
short stature

Endocrine Features:
diabetes insipidus
endocrine dysgenesis
pituitary agenesis
hypophyseal agenesis
hypothalamic dysfunction
more
Head And Neck Nose:
arrhinia
blind-ending proboscis
agenesis of nasal bones

Head And Neck Teeth:
central incisor

Head And Neck Head:
microcephaly
ethmocephaly
cebocephaly

Head And Neck Eyes:
microphthalmia
cyclopia
ocular hypotelorism
colobomata
varying degrees of doubling of intrinsic ocular structures

Head And Neck Face:
facial cleft
midface hypoplasia
premaxillary agenesis

Head And Neck Mouth:
median cleft lip/palate


Clinical features from OMIM:

236100

Human phenotypes related to Holoprosencephaly 1:

32 (show all 23)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 32 HP:0001274
2 intellectual disability 32 HP:0001249
3 seizures 32 HP:0001250
4 global developmental delay 32 HP:0001263
5 microcephaly 32 HP:0000252
6 short stature 32 HP:0004322
7 hypoglycemia 32 HP:0001943
8 cerebellar hypoplasia 32 HP:0001321
9 microphthalmia 32 HP:0000568
10 diabetes insipidus 32 HP:0000873
11 midface retrusion 32 HP:0011800
12 hypotelorism 32 HP:0000601
13 micropenis 32 HP:0000054
14 generalized hypotonia 32 HP:0001290
15 facial cleft 32 HP:0002006
16 median cleft lip and palate 32 HP:0008501
17 cyclopia 32 HP:0009914
18 adrenal hypoplasia 32 HP:0000835
19 aplasia of the nose 32 HP:0009927
20 proboscis 32 HP:0012806
21 ethmocephaly 32 HP:0030779
22 single ventricle 32 HP:0001750
23 alobar holoprosencephaly 32 HP:0006988

MGI Mouse Phenotypes related to Holoprosencephaly 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 vision/eye MP:0005391 9.17 AIRE CSTB GAS1 LSS SHH SIX3

Drugs & Therapeutics for Holoprosencephaly 1

Drugs for Holoprosencephaly 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Tobramycin Approved, Investigational Phase 1, Phase 2,Phase 2 32986-56-4 36294 5496
2
Minocycline Approved, Investigational Phase 1, Phase 2 10118-90-8 5281021
3 Anti-Infective Agents Phase 1, Phase 2,Phase 2
4 Anti-Bacterial Agents Phase 1, Phase 2,Phase 2
5
Caffeine Approved Not Applicable 58-08-2 2519
6
Clopidogrel Approved Not Applicable 113665-84-2, 120202-66-6 60606
7 Phosphodiesterase Inhibitors Not Applicable
8 Neurotransmitter Agents Not Applicable
9 Purinergic P1 Receptor Antagonists Not Applicable
10 Central Nervous System Stimulants Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis Completed NCT02035488 Phase 1, Phase 2 Tobramycin
2 DPI-Tobra-Kind Cyclops® in Children With Cystic Fibrosis Recruiting NCT03485456 Phase 1, Phase 2 Tobramycin
3 "Potential Effect of Acute and Chronic Caffeine Administration on Platelet Reactivity in Patient With Coronary Artery Disease on Dual Antiplatelet Therapy" Unknown status NCT02054988 Not Applicable
4 The Study of Psychological Status in Monophthalmic Patients With Ocular Surgery Recruiting NCT03603067

Search NIH Clinical Center for Holoprosencephaly 1

Genetic Tests for Holoprosencephaly 1

Genetic tests related to Holoprosencephaly 1:

# Genetic test Affiliating Genes
1 Holoprosencephaly 1 29
2 Cyclopia 29

Anatomical Context for Holoprosencephaly 1

MalaCards organs/tissues related to Holoprosencephaly 1:

41
Brain, Olfactory Bulb, Parietal Lobe, Bone, Pituitary, Adrenal Gland, Pancreas

Publications for Holoprosencephaly 1

Articles related to Holoprosencephaly 1:

(show all 30)
# Title Authors Year
1
Atypical synophthalmos with arhinencephaly unilateralis. ( 17913178 )
2007
2
Genetic susceptibility in the neural tube defects induced by ochratoxin A in the genetic arhinencephaly mouse, Pdn/Pdn. ( 16922921 )
2006
3
Suckling dysfunction caused by defects in the olfactory system in genetic arhinencephaly mice. ( 11093009 )
2000
4
Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum? ( 1734299 )
1992
5
Histopathological study of alobar holoprosencephaly. 1. Abnormal laminar architecture of the telencephalic cortex. ( 2750487 )
1989
6
Arhinencephaly. The spectrum of associated malformations. ( 3801853 )
1987
7
The arhinencephaly field defect. ( 3146302 )
1986
8
Arhinencephaly unilateralis. ( 6662578 )
1983
9
Bilateral cystic nephroblastomas and botryoid sarcoma involving vagina and urinary bladder in a child with microcephaly, arhinencephaly, and bilateral cataracts. ( 6268275 )
1981
10
Absent left hemidiaphragm, arhinencephaly, and cardiac malformations. ( 739533 )
1978
11
Arhinencephaly (holoprosencephaly) associated with external hydrocephaly. ( 605799 )
1977
12
Unilateral arhinencephaly in goldenhar-gorlin syndrome. ( 1158056 )
1975
13
Clinical and neuropathological investigations of four cases of holoprosencephaly with arhinencephaly. ( 5001028 )
1970
14
Arhinencephaly and its clinical significance. ( 4384000 )
1967
15
The radiological appearances in arhinencephaly. ( 5299683 )
1967
16
Holoprosencephaly/arhinencephaly: a case with no biochemical abnormalities. ( 5910775 )
1966
17
Roentgenology of holoprosencephaly (arhinencephaly). ( 5957829 )
1966
18
ARHINENCEPHALY-A SHORT REVIEW. ( 14286936 )
1965
19
FAMILIAL SHORT ARM DEFICIENCY OF CHROMOSOME 18 CONCOMITANT WITH ARHINENCEPHALY AND ALOPECIA CONGENITA. ( 14334740 )
1965
20
EEG IN HOLOPROSENCEPHALY (ARHINENCEPHALY). ( 14200659 )
1964
21
THE FACE PREDICTS THE BRAIN: DIAGNOSTIC SIGNIFICANCE OF MEDIAN FACIAL ANOMALIES FOR HOLOPROSENCEPHALY (ARHINENCEPHALY). ( 14211086 )
1964
22
A 46 CHROMOSOME CEBOCEPHALY, WITH REMARKS ON THE RELATION OF 13-15 TRISOMY TO HOLOPROSENCEPHALY (ARHINENCEPHALY). ( 14212871 )
1964
23
Arhinencephaly. ( 13928435 )
1963
24
Arhinencephaly, cyclopia and multiple congenital anomalies with endocrine dysgenesis. ( 13988355 )
1963
25
Meningeal angiomatosis, arhinencephaly, agenesis of the corpus callosum and large hamartoma of the brain, with neoplasia, in an infant having bilateral nasal proboscis. ( 13705778 )
1960
26
Orbital hypotelorism, arhinencephaly, and trigonocephaly. ( 13813361 )
1960
27
Arhinencephaly in an infant born to a diabetic mother. ( 13815477 )
1959
28
Arhinencephaly. ( 13594961 )
1958
29
Arhinencephaly and multiple developmental anomalies occurring in a human full-term foetus. ( 20238492 )
1947
30
ARHINENCEPHALY. ( 21610958 )
1939

Variations for Holoprosencephaly 1

ClinVar genetic disease variations for Holoprosencephaly 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GAS1 NM_002048.2(GAS1): c.599C> G (p.Thr200Arg) single nucleotide variant Uncertain significance rs387907165 GRCh37 Chromosome 9, 89561096: 89561096
2 GAS1 NM_002048.2(GAS1): c.599C> G (p.Thr200Arg) single nucleotide variant Uncertain significance rs387907165 GRCh38 Chromosome 9, 86946181: 86946181
3 GAS1 NM_002048.2(GAS1): c.776G> A (p.Gly259Glu) single nucleotide variant Uncertain significance rs387907166 GRCh37 Chromosome 9, 89560919: 89560919
4 GAS1 NM_002048.2(GAS1): c.776G> A (p.Gly259Glu) single nucleotide variant Uncertain significance rs387907166 GRCh38 Chromosome 9, 86946004: 86946004

Expression for Holoprosencephaly 1

Search GEO for disease gene expression data for Holoprosencephaly 1.

Pathways for Holoprosencephaly 1

Pathways related to Holoprosencephaly 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.1 GAS1 SHH

GO Terms for Holoprosencephaly 1

Biological processes related to Holoprosencephaly 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of cell proliferation GO:0042127 9.54 CELA1 SHH SIX3
2 developmental growth GO:0048589 9.32 GAS1 SHH
3 anatomical structure development GO:0048856 9.26 SHH SIX3
4 embryonic pattern specification GO:0009880 9.16 SHH SIM2
5 negative thymic T cell selection GO:0045060 8.96 AIRE SHH
6 telencephalon regionalization GO:0021978 8.62 SHH SIX3

Molecular functions related to Holoprosencephaly 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serine-type peptidase activity GO:0008236 8.8 CELA1 CELA3A CELA3B

Sources for Holoprosencephaly 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....