MCID: HLP023
MIFTS: 44

Holoprosencephaly 1

Categories: Neuronal diseases, Genetic diseases, Rare diseases, Endocrine diseases, Fetal 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 alobar holoprosencephaly and 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 Anti-Bacterial Agents have been mentioned in the context of this disorder. Affiliated tissues include olfactory bulb, brain and parietal lobe, and related phenotypes are micropenis and microcephaly

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

Related Diseases for Holoprosencephaly 1

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

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

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
Olfactory Bulb, Brain, Parietal Lobe, Pituitary, Adrenal Gland, Bone, Cortex

Publications for Holoprosencephaly 1

Articles related to Holoprosencephaly 1:

# Title Authors Year
1
Histopathological study of alobar holoprosencephaly. 1. Abnormal laminar architecture of the telencephalic cortex. ( 2750487 )
1989

Variations for Holoprosencephaly 1

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
10.14 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 developmental growth GO:0048589 9.26 GAS1 SHH
2 embryonic pattern specification GO:0009880 9.16 SHH SIM2
3 negative thymic T cell selection GO:0045060 8.96 AIRE SHH
4 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
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