HOLOPROSENCEPHALY 2

General Information (adopted from Orphanet):

Synonyms, Signs: HPE2
Number of Symptoms 47
OrphanetNr:
OMIM Id: 157170
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant inheritance
Heterogeneous
Sporadic
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Symptom Information: Sort by abundance 

1
(HPO:0005273) Absent nasal septal cartilage 4 / 7739
2
(HPO:0000272) Malar flattening 277 / 7739
3
(HPO:0006315) Single median maxillary incisor 13 / 7739
4
(HPO:0008501) Median cleft lip and palate 7 / 7739
5
(HPO:0009927) Aplasia of the nose 3 / 7739
6
(HPO:0000601) Hypotelorism 83 / 7739
7
(HPO:0000193) Bifid uvula 66 / 7739
8
(HPO:0011800) Midface retrusion 221 / 7739
9
(HPO:0000568) Microphthalmia 183 / 7739
10
(HPO:0000252) Microcephaly 832 / 7739
11
(HPO:0000176) Submucous cleft hard palate 19 / 7739
12
(HPO:0009914) Cyclopia 11 / 7739
13
(HPO:0000589) Coloboma 47 / 7739
14
(HPO:0001249) Intellectual disability 1089 / 7739
15
(HPO:0001263) Global developmental delay 853 / 7739
16
(HPO:0001250) Seizures 1245 / 7739
17
(HPO:0010626) Anterior pituitary agenesis 2 / 7739
18
(HPO:0000873) Diabetes insipidus 34 / 7739
19
(HPO:0000835) Adrenal hypoplasia 23 / 7739
20
(HPO:0002650) Scoliosis 705 / 7739
21
(HPO:0002019) Constipation 194 / 7739
22
(HPO:0001324) Muscle weakness 859 / 7739
23
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
24
(HPO:0010547) Muscle flaccidity 466 / 7739
25
(HPO:0001252) Muscular hypotonia 990 / 7739
26
(HPO:0003829) Incomplete penetrance 85 / 7739
27
(HPO:0001425) Heterogeneous 132 / 7739
28
(HPO:0002139) Arrhinencephaly 13 / 7739
29
(OMIM) Hypothalamic dysfunction 4 / 7739
30
(OMIM) Agenesis of nasal bones 2 / 7739
31
(OMIM) Atelencephaly 1 / 7739
32
(OMIM) Varying degrees of doubling of intrinsic ocular structures 1 / 7739
33
(HPO:0001321) Cerebellar hypoplasia 114 / 7739
34
(HPO:0001274) Agenesis of corpus callosum 142 / 7739
35
(OMIM) Pituitary agenesis 3 / 7739
36
(HPO:0003828) Variable expressivity 130 / 7739
37
(OMIM) Blind-ending proboscis 1 / 7739
38
(HPO:0000006) Autosomal dominant inheritance 2518 / 7739
39
(OMIM) Lobar HPE shows clear interhemispheric fissure and 2 lateral ventricles 1 / 7739
40
(OMIM) Premaxillary agenesis 1 / 7739
41
(OMIM) Semilobar HPE shows posterior interhemispheric fissure with rudimentary cerebral hemispheres and single ventricle 1 / 7739
42
(HPO:0001360) Holoprosencephaly 29 / 7739
43
(OMIM) Endocrine dysgenesis 2 / 7739
44
(OMIM) Hypophyseal agenesis 1 / 7739
45
(OMIM) Alobar HPE shows absence of interhemispheric cleavage and single ventricle 1 / 7739
46
(HPO:0003745) Sporadic 131 / 7739
47
(OMIM) Central incisor 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Martin et al. (1977) described a kindred with 7 persons affected with a syndrome manifested by cleft lip and anterior cleft palate, hypotelorism, microcephaly, mental retardation, scoliosis, and chronic constipation. The disorder bore similarities to familial holoprosencephaly. Three ...
Genotype-Phenotype Correlations OMIM Among 34 patients with holoprosencephaly, Dubourg et al. (2004) observed that mutation in the SIX3 gene was associated with atelencephaly.

Lacbawan et al. (2009) identified SIX3 mutations in 4.7% of 800 probands and relatives with HPE. ...

Molecular genetics OMIM Wallis et al. (1999) demonstrated mutations in the SIX3 gene (603714.0001-603714.0003) in patients with holoprosencephaly.

In 6 Brazilian patients with HPE2, Ribeiro et al. (2006) identified 5 missense mutations and 2 frameshift mutations in the SIX3 ...

Population genetics OMIM In a targeted screening study of 4 genes in 186 Dutch patients with holoprosencephaly, Paulussen et al. (2010) found that 21 (24%) had heterozygous mutations in 1 of 3 of the genes. Three (3.5%) had mutations in the ...