MCID: AGN012
MIFTS: 51

Agnathia-Otocephaly Complex

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

Aliases & Classifications for Agnathia-Otocephaly Complex

MalaCards integrated aliases for Agnathia-Otocephaly Complex:

Name: Agnathia-Otocephaly Complex 53 12 71 13 14
Otocephaly 53 12 71 69
Dysgnathia Complex Agnathia-Holoprosencephaly 53 12 71
Holoprosencephaly-Agnathia 53 12 71
Agnathia-Holoprosencephaly-Situs Inversus Syndrome 12 55
Agotc 53 71
Dysgnathia Complex 69
Jaw Abnormalities 41

Characteristics:

Orphanet epidemiological data:

55
agnathia-holoprosencephaly-situs inversus syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM:

53
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable phenotype
de novo mutation in most cases
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:

31
agnathia-otocephaly complex:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Agnathia-Otocephaly Complex

OMIM : 53 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 auriculocondylar syndrome 1, and has symptoms including respiratory distress, agenesis of corpus callosum and abnormality of the eye. 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:

53
Respiratory:
respiratory distress

Respiratory Airways:
tracheomalacia
blind-ended trachea

Head And Neck Eyes:
downslanting palpebral fissures
synophthalmia

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

Head And Neck Nose:
frontal proboscis

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

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

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

Head And Neck Face:
mandibular hypoplasia
mandibular agenesis
agnathia

Head And Neck Head:
otocephaly

Abdomen:
situs inversus (variable)


Clinical features from OMIM:

202650

Human phenotypes related to Agnathia-Otocephaly Complex:

55 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 respiratory distress 55 31 hallmark (90%) Very frequent (99-80%) HP:0002098
2 agenesis of corpus callosum 55 31 hallmark (90%) Very frequent (99-80%) HP:0001274
3 abnormality of the eye 55 31 Very frequent (99-80%) HP:0000478
4 aplasia/hypoplasia of the cerebellum 55 31 hallmark (90%) Very frequent (99-80%) HP:0007360
5 low-set, posteriorly rotated ears 55 31 hallmark (90%) Very frequent (99-80%) HP:0000368
6 narrow mouth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000160
7 polyhydramnios 55 31 hallmark (90%) Very frequent (99-80%) HP:0001561
8 hypoplasia of penis 55 31 hallmark (90%) Very frequent (99-80%) HP:0008736
9 holoprosencephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001360
10 aplasia/hypoplasia of the eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0100840
11 narrow internal auditory canal 55 31 hallmark (90%) Very frequent (99-80%) HP:0011386
12 situs inversus totalis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001696
13 cyclopia 55 31 hallmark (90%) Very frequent (99-80%) HP:0009914
14 aplasia/hypoplasia involving the nose 55 31 hallmark (90%) Very frequent (99-80%) HP:0009924
15 absent nares 55 31 hallmark (90%) Very frequent (99-80%) HP:0100596
16 abnormality of the cranial nerves 55 31 hallmark (90%) Very frequent (99-80%) HP:0001291
17 microglossia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000171
18 mandibular aplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0009939
19 synotia 55 31 hallmark (90%) Very frequent (99-80%) HP:0100663
20 cleft palate 31 HP:0000175
21 micrognathia 31 HP:0000347
22 downslanted palpebral fissures 31 HP:0000494
23 conductive hearing impairment 31 HP:0000405
24 tracheomalacia 31 HP:0002779
25 laryngeal hypoplasia 31 HP:0008749
26 hypoplasia of the epiglottis 31 HP:0005349
27 aglossia 31 HP:0012730

UMLS symptoms related to Agnathia-Otocephaly Complex:


respiratory distress

MGI Mouse Phenotypes related to Agnathia-Otocephaly Complex:

43 (show all 19)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.41 ALX3 BMP4 CRKL DCX FGF8 GLI2
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 PLCB4 PRRX1 SHH ALX3 BMP4 CRKL
6 digestive/alimentary MP:0005381 10.33 BMP4 FGF8 GLI2 HHAT MSX1 NODAL
7 cardiovascular system MP:0005385 10.27 HHAT LBX1 MSX1 NODAL OTX2 PRRX1
8 nervous system MP:0003631 10.27 DCX FGF8 GLI2 HHAT LBX1 MSX1
9 endocrine/exocrine gland MP:0005379 10.26 OTX1 OTX2 PGAP1 SHH ALX3 BMP4
10 cellular MP:0005384 10.22 GLI2 LBX1 NODAL ALX3 BMP4 FGF8
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 normal MP:0002873 9.92 BMP4 FGF8 GLI2 LBX1 MSX1 NODAL
17 respiratory system MP:0005388 9.9 ALX3 BMP4 FGF8 GLI2 HHAT MSX1
18 skeleton MP:0005390 9.8 FGF8 GLI2 HHAT MSX1 NODAL OTX1
19 vision/eye MP:0005391 9.47 CRKL FGF8 GLI2 HHAT MSX1 NODAL

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

Anatomical Context for Agnathia-Otocephaly Complex

MalaCards organs/tissues related to Agnathia-Otocephaly Complex:

38
Trachea, Eye, Cerebellum

Publications for Agnathia-Otocephaly Complex

Articles related to Agnathia-Otocephaly Complex:

# Title Authors Year
1
Cyclopia: isolated and with agnathia-otocephaly complex. ( 28855214 )
2017
2
Severe Agnathia-Otocephaly Complex: Surgical Management and Longitudinal Follow-Up of 4 Patients from Birth Through Adulthood. ( 26397488 )
2015
3
Severe Agnathia-Otocephaly Complex: Surgical Management and Longitudinal Follow-up From Birth Through Adulthood. ( 26517463 )
2015
4
Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an in-frame duplication in OTX2. ( 25589041 )
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
# Symbol AA change Variation ID SNP ID
1 PRRX1 p.Phe113Ser VAR_066414 rs387906667

ClinVar genetic disease variations for Agnathia-Otocephaly Complex:

6
# 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)
# 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 9.89 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 cell fate commitment GO:0045165 9.84 BMP4 FGF8 NODAL 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 odontogenesis of dentin-containing tooth GO:0042475 9.83 BMP4 GLI2 MSX1 SHH
20 branching morphogenesis of an epithelial tube GO:0048754 9.82 BMP4 GLI2 SHH
21 embryonic pattern specification GO:0009880 9.81 NODAL PGAP1 SHH
22 pattern specification process GO:0007389 9.81 ALX3 CRKL GLI2 SHH
23 vasculature development GO:0001944 9.8 BMP4 NODAL SHH
24 dopaminergic neuron differentiation GO:0071542 9.8 FGF8 OTX2 SHH
25 embryonic limb morphogenesis GO:0030326 9.8 BMP4 MSX1 PRRX1 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 thyroid gland development GO:0030878 9.76 FGF8 SHH
35 renal system development GO:0072001 9.76 BMP4 SHH
36 hindbrain development GO:0030902 9.76 GLI2 SHH
37 regulation of smoothened signaling pathway GO:0008589 9.76 GLI2 OTX2
38 embryonic heart tube development GO:0035050 9.76 FGF8 NODAL
39 dorsal/ventral neural tube patterning GO:0021904 9.76 BMP4 GLI2 SHH
40 embryonic cranial skeleton morphogenesis GO:0048701 9.76 ALX3 BMP4 NODAL PRRX1
41 signal transduction involved in regulation of gene expression GO:0023019 9.75 FGF8 MSX1
42 male genitalia development GO:0030539 9.75 FGF8 SHH
43 middle ear morphogenesis GO:0042474 9.75 MSX1 PRRX1
44 negative regulation of chondrocyte differentiation GO:0032331 9.75 BMP4 GLI2
45 osteoblast development GO:0002076 9.75 GLI2 SHH
46 prostate gland development GO:0030850 9.75 GLI2 SHH
47 epithelial tube branching involved in lung morphogenesis GO:0060441 9.75 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:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.46 GLI2 OTX1 OTX2 PRRX1
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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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