Agnathia - holoprosencephaly - situs inversus

General Information (adopted from Orphanet):

Synonyms, Signs: HOLOPROSENCEPHALY-AGNATHIA
OTOCEPHALY
DYSGNATHIA COMPLEX AGNATHIA-HOLOPROSENCEPHALY
AGOTC
Number of Symptoms 47
OrphanetNr: 990
OMIM Id: 202650
ICD-10: Q87.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 30 cases [Orphanet]
Inheritance: Unknown
Not applicable
[Orphanet]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare genetic intellectual deficit with developmental anomaly
 -Rare genetic disease
Rare intellectual deficit with developmental anomaly
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000054) Micropenis Very frequent [Orphanet] 257 / 7739
2
 (HPO:0009914) Cyclopia Very frequent [Orphanet] 11 / 7739
3
 (HPO:0100840) Aplasia/Hypoplasia of the eyebrow Very frequent [Orphanet] 117 / 7739
4
 (HPO:0009932) Single naris Very frequent [Orphanet] 10 / 7739
5
 (HPO:0000171) Microglossia Very frequent [Orphanet] 27 / 7739
6
 (HPO:0009924) Aplasia/Hypoplasia involving the nose Very frequent [Orphanet] 18 / 7739
7
 (HPO:0000606) Abnormality of the periorbital region Very frequent [Orphanet] 96 / 7739
8
 (HPO:0000347) Micrognathia 426 / 7739
9
 (HPO:0000494) Downslanted palpebral fissures 328 / 7739
10
 (HPO:0000160) Narrow mouth Very frequent [Orphanet] 188 / 7739
11
 (HPO:0000308) Microretrognathia Very frequent [Orphanet] 78 / 7739
12
 (HPO:0000175) Cleft palate 349 / 7739
13
 (HPO:0000478) Abnormality of the eye 126 / 7739
14
 (HPO:0000357) Abnormal location of ears Very frequent [Orphanet] 328 / 7739
15
 (HPO:0000356) Abnormality of the outer ear 85 / 7739
16
 (HPO:0100663) Synotia Very frequent [Orphanet] 1 / 7739
17
 (HPO:0000405) Conductive hearing impairment 164 / 7739
18
 (HPO:0008772) Aplasia/Hypoplasia of the external ear Very frequent [Orphanet] 67 / 7739
19
 (HPO:0001291) Abnormality of the cranial nerves Very frequent [Orphanet] 27 / 7739
20
 (HPO:0001561) Polyhydramnios Very frequent [Orphanet] 191 / 7739
21
 (HPO:0001696) Situs inversus totalis 44 / 7739
22
 (HPO:0003363) Abdominal situs inversus Very frequent [Orphanet] 19 / 7739
23
 (HPO:0002093) Respiratory insufficiency Very frequent [Orphanet] 410 / 7739
24
 (HPO:0005349) Hypoplasia of the epiglottis 7 / 7739
25
 (HPO:0008749) Laryngeal hypoplasia 5 / 7739
26
 (HPO:0002098) Respiratory distress 75 / 7739
27
 (HPO:0002779) Tracheomalacia 26 / 7739
28
 (HPO:0012443) Abnormality of brain morphology Very frequent [Orphanet] 45 / 7739
29
 (OMIM) Frontal proboscis 1 / 7739
30
 (OMIM) Trachea-oropharynx connection agenesis 1 / 7739
31
 (OMIM) Mandibular agenesis 3 / 7739
32
 (HPO:0002334) Abnormality of the cerebellar vermis Very frequent [Orphanet] 137 / 7739
33
 (HPO:0012730) Aglossia 3 / 7739
34
 (OMIM) Hypoplastic oropharynx 1 / 7739
35
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
36
 (OMIM) Blind-ended trachea 1 / 7739
37
 (HPO:0011420) Death Very frequent [Orphanet] 184 / 7739
38
 (MedDRA:10001501) Aglossia 2 / 7739
39
 (OMIM) Agnathia 1 / 7739
40
 (OMIM) Synophthalmia 1 / 7739
41
 (HPO:0001360) Holoprosencephaly 29 / 7739
42
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
43
 (HPO:0002139) Arrhinencephaly 13 / 7739
44
 (HPO:0003812) Phenotypic variability 129 / 7739
45
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739
46
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Very frequent [Orphanet] 180 / 7739
47
 (MedDRA:10058118) Otocephaly 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Agnathia-otocephaly is a rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular ...
Clinical Description OMIM Pauli et al. (1983) described an agnathia-holoprosencephaly syndrome in 2 stillborn sisters. One sister also had cardiac anomalies, stage-2 malrotation of the gut with a common mesentery, and a hypoplastic right kidney. The other sister had complete agenesis ...
Molecular genetics OMIM In a fetus with agnathia-otocephaly complex reported by Schiffer et al. (2002), Sergi and Kamnasaran (2011) identified a heterozygous loss-of-function mutation in the PRRX1 gene (F113S; 167420.0001). The PRRX1 gene was selected for sequencing because of its known ...
Population genetics OMIM Faye-Petersen et al. (2006) stated that otocephaly is identified in less than 1 in 70,000 births.