MCID: AGN012
MIFTS: 48

Agnathia-Otocephaly Complex

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

Aliases & Classifications for Agnathia-Otocephaly Complex

MalaCards integrated aliases for Agnathia-Otocephaly Complex:

Name: Agnathia-Otocephaly Complex 54 12 24 71 13 14
Otocephaly 12 71 69
Agnathia-Holoprosencephaly-Situs Inversus Syndrome 12 56
Dysgnathia Complex Agnathia-Holoprosencephaly 12 71
Holoprosencephaly-Agnathia 12 71
Dysgnathia Complex 69
Jaw Abnormalities 42
Agotc 71

Characteristics:

Orphanet epidemiological data:

56
agnathia-holoprosencephaly-situs inversus syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive

Miscellaneous:
variable phenotype
most cases occur de novo
autosomal recessive inheritance has been reported in 1 case
usually lethal in the neonatal period
incidence is less than 1 in 70,000 births


HPO:

32
agnathia-otocephaly complex:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Agnathia-Otocephaly Complex

OMIM : 54
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 anomalies, and situs inversus have been reported. The disorder is almost always lethal (review by Faye-Petersen et al., 2006). (202650)

MalaCards based summary : Agnathia-Otocephaly Complex, also known as otocephaly, is related to dysgnathia complex and dysmorphism abnormal vocalization mental retardation, and has symptoms including polyhydramnios, respiratory distress and agenesis of corpus callosum. An important gene associated with Agnathia-Otocephaly Complex is PRRX1 (Paired Related Homeobox 1), and among its related pathways/superpathways are Pathways in cancer and Mesodermal Commitment Pathway. Affiliated tissues include trachea, eye and cerebellum, and related phenotypes are growth/size/body region and embryo

UniProtKB/Swiss-Prot : 71 Agnathia-otocephaly complex: 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 anomalies, and situs inversus have been reported. The disorder is almost always lethal.

Disease Ontology : 12 A physical disorder 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 anomalies and situs inversus have been reported.

Related Diseases for Agnathia-Otocephaly Complex

Graphical network of the top 20 diseases related to Agnathia-Otocephaly Complex:



Diseases related to Agnathia-Otocephaly Complex

Symptoms & Phenotypes for Agnathia-Otocephaly Complex

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Face:
mandibular hypoplasia
mandibular agenesis
agnathia

Respiratory:
respiratory distress

Head And Neck- Head:
otocephaly

Head And Neck- Nose:
frontal proboscis

Respiratory- Airways:
blind-ended trachea
tracheomalacia

Neurologic- Central Nervous System:
holoprosencephaly (variable)
agenesis of the corpus callosum (variable)

Head And Neck- Mouth:
cleft palate
microstomia
microglossia
aglossia
hypoplastic oropharynx

Head And Neck- Ears:
hearing loss, conductive
synotia
ear anomalies

Head And Neck- Eyes:
synophthalmia
downslanted palpebral fissures

Respiratory- Larynx:
hypoplastic epiglottis
hypoplastic larynx
trachea-oropharynx connection agenesis

Abdomen:
situs inversus (variable)


Clinical features from OMIM:

202650

Human phenotypes related to Agnathia-Otocephaly Complex:

56 32 (show all 27)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 polyhydramnios 56 32 hallmark (90%) Very frequent (99-80%) HP:0001561
2 respiratory distress 56 32 hallmark (90%) Very frequent (99-80%) HP:0002098
3 agenesis of corpus callosum 56 32 hallmark (90%) Very frequent (99-80%) HP:0001274
4 synotia 56 32 hallmark (90%) Very frequent (99-80%) HP:0100663
5 microglossia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000171
6 low-set, posteriorly rotated ears 56 32 hallmark (90%) Very frequent (99-80%) HP:0000368
7 holoprosencephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0001360
8 cyclopia 56 32 hallmark (90%) Very frequent (99-80%) HP:0009914
9 narrow mouth 56 32 hallmark (90%) Very frequent (99-80%) HP:0000160
10 hypoplasia of penis 56 32 hallmark (90%) Very frequent (99-80%) HP:0008736
11 abnormality of the eye 56 32 Very frequent (99-80%) HP:0000478
12 aplasia/hypoplasia of the cerebellum 56 32 hallmark (90%) Very frequent (99-80%) HP:0007360
13 aplasia/hypoplasia of the eyebrow 56 32 hallmark (90%) Very frequent (99-80%) HP:0100840
14 narrow internal auditory canal 56 32 hallmark (90%) Very frequent (99-80%) HP:0011386
15 situs inversus totalis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001696
16 aplasia/hypoplasia involving the nose 56 32 hallmark (90%) Very frequent (99-80%) HP:0009924
17 absent nares 56 32 hallmark (90%) Very frequent (99-80%) HP:0100596
18 abnormality of the cranial nerves 56 32 hallmark (90%) Very frequent (99-80%) HP:0001291
19 mandibular aplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0009939
20 micrognathia 32 HP:0000347
21 cleft palate 32 HP:0000175
22 laryngeal hypoplasia 32 HP:0008749
23 hypoplasia of the epiglottis 32 HP:0005349
24 downslanted palpebral fissures 32 HP:0000494
25 aglossia 32 HP:0012730
26 tracheomalacia 32 HP:0002779
27 conductive hearing impairment 32 HP:0000405

UMLS symptoms related to Agnathia-Otocephaly Complex:


respiratory distress

MGI Mouse Phenotypes related to Agnathia-Otocephaly Complex:

44 (show all 19)
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.41 FGF8 GLI2 HHAT LBX1 MSX1 NODAL
2 embryo MP:0005380 10.38 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
3 craniofacial MP:0005382 10.37 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
4 behavior/neurological MP:0005386 10.36 ALX3 BMP4 DCX FGF8 GLI2 LBX1
5 mortality/aging MP:0010768 10.34 GLI2 HHAT LBX1 MSX1 NODAL OTX1
6 digestive/alimentary MP:0005381 10.33 ALX3 BMP4 FGF8 GLI2 HHAT MSX1
7 cardiovascular system MP:0005385 10.27 BMP4 CRKL FGF8 HHAT LBX1 MSX1
8 nervous system MP:0003631 10.27 HHAT LBX1 MSX1 NODAL OTX1 OTX2
9 endocrine/exocrine gland MP:0005379 10.26 GLI2 HHAT MSX1 OTX1 OTX2 PGAP1
10 cellular MP:0005384 10.22 OTX2 SHH ALX3 BMP4 FGF8 GLI2
11 homeostasis/metabolism MP:0005376 10.22 ALX3 BMP4 FGF8 GLI2 HHAT MSX1
12 hearing/vestibular/ear MP:0005377 10.19 BMP4 CRKL FGF8 GLI2 MSX1 OTX1
13 limbs/digits/tail MP:0005371 10.16 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
14 muscle MP:0005369 10.06 BMP4 FGF8 GLI2 LBX1 MSX1 NODAL
15 reproductive system MP:0005389 10 ALX3 BMP4 DCX FGF8 GLI2 HHAT
16 respiratory system MP:0005388 9.9 OTX2 PGAP1 PRRX1 SHH ALX3 BMP4
17 normal MP:0002873 9.87 BMP4 FGF8 GLI2 LBX1 NODAL OTX2
18 skeleton MP:0005390 9.8 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
19 vision/eye MP:0005391 9.47 MSX1 NODAL OTX1 OTX2 PGAP1 PLCB4

Drugs & Therapeutics for Agnathia-Otocephaly Complex

Search Clinical Trials , NIH Clinical Center for Agnathia-Otocephaly Complex

Cochrane evidence based reviews: jaw abnormalities

Genetic Tests for Agnathia-Otocephaly Complex

Genetic tests related to Agnathia-Otocephaly Complex:

id Genetic test Affiliating Genes
1 Agnathia-Otocephaly Complex 24 PRRX1

Anatomical Context for Agnathia-Otocephaly Complex

MalaCards organs/tissues related to Agnathia-Otocephaly Complex:

39
Trachea, Eye, Cerebellum

Publications for Agnathia-Otocephaly Complex

Articles related to Agnathia-Otocephaly Complex:

id Title Authors Year
1
Cyclopia: isolated and with agnathia-otocephaly complex. ( 28855214 )
2017
2
Severe Agnathia-Otocephaly Complex: Surgical Management and Longitudinal Follow-up From Birth Through Adulthood. ( 26517463 )
2015
3
Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an in-frame duplication in OTX2. ( 25589041 )
2015
4
Severe Agnathia-Otocephaly Complex: Surgical Management and Longitudinal Follow-Up of 4 Patients from Birth Through Adulthood. ( 26397488 )
2015
5
Agnathia-otocephaly complex: a case report and examination of the OTX2 and PRRX1 genes. ( 22198066 )
2012
6
Agnathia-otocephaly complex in a fetus with maternal use of topical 1% salicylate. ( 18049088 )
2008
7
A case of agnathia-otocephaly complex assessed prenatally for ex utero intrapartum treatment (EXIT) by three-dimensional ultrasonography. ( 17497748 )
2007
8
Agnathia-otocephaly complex: report of three cases with involvement of two different Carnegie stages. ( 12244557 )
2002

Variations for Agnathia-Otocephaly Complex

UniProtKB/Swiss-Prot genetic disease variations for Agnathia-Otocephaly Complex:

71
id Symbol AA change Variation ID SNP ID
1 PRRX1 p.Phe113Ser VAR_066414 rs387906667

ClinVar genetic disease variations for Agnathia-Otocephaly Complex:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 PRRX1 NM_006902.4(PRRX1): c.338T> C (p.Phe113Ser) single nucleotide variant Pathogenic rs387906667 GRCh37 Chromosome 1, 170688963: 170688963
2 PRRX1 PRRX1, ALA231PRO single nucleotide variant Pathogenic
3 PRRX1 NM_006902.4(PRRX1): c.269delA (p.Lys90Argfs) deletion Pathogenic rs398122375 GRCh37 Chromosome 1, 170688894: 170688894
4 PRRX1 NM_006902.4(PRRX1): c.266_269dupAAAA (p.Arg92Glufs) duplication Pathogenic rs398122376 GRCh37 Chromosome 1, 170688891: 170688894

Expression for Agnathia-Otocephaly Complex

Search GEO for disease gene expression data for Agnathia-Otocephaly Complex.

Pathways for Agnathia-Otocephaly Complex

GO Terms for Agnathia-Otocephaly Complex

Biological processes related to Agnathia-Otocephaly Complex according to GeneCards Suite gene sharing:

(show top 50) (show all 85)
id Name GO ID Score Top Affiliating Genes
1 kidney development GO:0001822 9.93 BMP4 FGF8 GLI2 SHH
2 BMP signaling pathway GO:0030509 9.91 BMP4 FGF8 MSX1 NODAL
3 palate development GO:0060021 9.9 MSX1 PRRX1 SHH
4 cartilage development GO:0051216 9.9 BMP4 MSX1 PRRX1
5 determination of left/right symmetry GO:0007368 9.9 FGF8 NODAL SHH
6 inner ear morphogenesis GO:0042472 9.9 FGF8 OTX1 PRRX1
7 smoothened signaling pathway GO:0007224 9.88 BMP4 GLI2 HHAT SHH
8 embryonic skeletal system morphogenesis GO:0048704 9.87 ALX3 BMP4 PRRX1
9 positive regulation of cell differentiation GO:0045597 9.87 BMP4 FGF8 SHH
10 heart looping GO:0001947 9.86 FGF8 LBX1 NODAL SHH
11 branching involved in ureteric bud morphogenesis GO:0001658 9.85 BMP4 FGF8 SHH
12 embryonic digit morphogenesis GO:0042733 9.85 BMP4 GLI2 MSX1 SHH
13 metanephros development GO:0001656 9.84 BMP4 FGF8 SHH
14 protein localization to nucleus GO:0034504 9.84 BMP4 MSX1 SHH
15 odontogenesis of dentin-containing tooth GO:0042475 9.84 BMP4 GLI2 MSX1 SHH
16 embryonic forelimb morphogenesis GO:0035115 9.83 ALX3 MSX1 SHH
17 neuron fate commitment GO:0048663 9.83 BMP4 LBX1 SHH
18 pituitary gland development GO:0021983 9.83 BMP4 GLI2 MSX1
19 cell fate commitment GO:0045165 9.83 BMP4 FGF8 NODAL SHH
20 branching morphogenesis of an epithelial tube GO:0048754 9.82 BMP4 GLI2 SHH
21 embryonic pattern specification GO:0009880 9.82 NODAL PGAP1 SHH
22 embryonic limb morphogenesis GO:0030326 9.81 BMP4 MSX1 PRRX1 SHH
23 vasculature development GO:0001944 9.8 BMP4 NODAL SHH
24 dopaminergic neuron differentiation GO:0071542 9.8 FGF8 OTX2 SHH
25 pattern specification process GO:0007389 9.8 ALX3 CRKL GLI2 SHH
26 lung development GO:0030324 9.8 BMP4 FGF8 GLI2 NODAL SHH
27 heart development GO:0007507 9.8 BMP4 CRKL FGF8 GLI2 MSX1 NODAL
28 lung morphogenesis GO:0060425 9.79 BMP4 FGF8 SHH
29 spinal cord motor neuron differentiation GO:0021522 9.78 GLI2 LBX1 SHH
30 midbrain development GO:0030901 9.78 MSX1 OTX1 OTX2 SHH
31 anterior/posterior axis specification GO:0009948 9.77 BMP4 NODAL PGAP1
32 forebrain development GO:0030900 9.77 BMP4 MSX1 OTX1 OTX2 SHH
33 outflow tract septum morphogenesis GO:0003148 9.76 BMP4 FGF8
34 positive regulation of smoothened signaling pathway GO:0045880 9.76 PRRX1 SHH
35 thyroid gland development GO:0030878 9.76 FGF8 SHH
36 hindbrain development GO:0030902 9.76 GLI2 SHH
37 renal system development GO:0072001 9.76 BMP4 SHH
38 regulation of smoothened signaling pathway GO:0008589 9.76 GLI2 OTX2
39 embryonic cranial skeleton morphogenesis GO:0048701 9.76 ALX3 BMP4 NODAL PRRX1
40 signal transduction involved in regulation of gene expression GO:0023019 9.75 FGF8 MSX1
41 middle ear morphogenesis GO:0042474 9.75 MSX1 PRRX1
42 embryonic heart tube development GO:0035050 9.75 FGF8 NODAL
43 male genitalia development GO:0030539 9.75 FGF8 SHH
44 negative regulation of chondrocyte differentiation GO:0032331 9.75 BMP4 GLI2
45 osteoblast development GO:0002076 9.75 GLI2 SHH
46 dorsal/ventral neural tube patterning GO:0021904 9.75 BMP4 GLI2 SHH
47 epithelial tube branching involved in lung morphogenesis GO:0060441 9.74 BMP4 SHH
48 anatomical structure development GO:0048856 9.74 GLI2 SHH
49 embryonic morphogenesis GO:0048598 9.74 BMP4 SHH
50 head development GO:0060322 9.74 GLI2 PGAP1

Molecular functions related to Agnathia-Otocephaly Complex according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000978 9.33 GLI2 OTX1 OTX2
2 sequence-specific DNA binding GO:0043565 9.17 ALX3 GLI2 LBX1 MSX1 OTX1 OTX2
3 morphogen activity GO:0016015 8.96 NODAL SHH

Sources for Agnathia-Otocephaly Complex

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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