MCID: AGN012
MIFTS: 51

Agnathia-Otocephaly Complex

Categories: Genetic diseases, Immune diseases, Blood 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 57 12 75 13 15
Otocephaly 57 12 75 73
Dysgnathia Complex Agnathia-Holoprosencephaly 57 12 75
Holoprosencephaly-Agnathia 57 12 75
Agnathia-Holoprosencephaly-Situs Inversus Syndrome 12 59
Agotc 57 75
Dysgnathia Complex 73
Jaw Abnormalities 44

Characteristics:

Orphanet epidemiological data:

59
agnathia-holoprosencephaly-situs inversus syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM:

57
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:

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


Classifications:



Summaries for Agnathia-Otocephaly Complex

OMIM : 57 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 holoprosencephaly, and has symptoms including respiratory distress 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, cerebellum and eye, and related phenotypes are narrow mouth and microglossia

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.

UniProtKB/Swiss-Prot : 75 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.

Related Diseases for Agnathia-Otocephaly Complex

Diseases related to Agnathia-Otocephaly Complex via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 dysgnathia complex 33.2 OTX2 PRRX1
2 holoprosencephaly 29.0 FGF8 GLI2 NODAL SHH
3 cerebrocostomandibular syndrome 10.7
4 maxillonasal dysplasia, binder type 10.3 ALX3 SHH
5 hemifacial microsomia 10.3 ALX3 OTX2
6 acromelic frontonasal dysostosis 10.3 ALX3 SHH
7 palatopharyngeal incompetence 10.2
8 combined pituitary hormone deficiencies, genetic forms 10.2 GLI2 OTX2
9 auriculocondylar syndrome 1 10.0
10 chromosome 18p deletion syndrome 9.9 NODAL SHH
11 infratentorial cancer 9.9 GLI2 OTX2 SHH
12 pallister-hall syndrome 9.7 GLI2 SHH
13 axenfeld-rieger syndrome, type 1 9.7 BMP4 FGF8 SHH
14 hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate 9.6 GLI2 MSX1 SHH
15 congenital nervous system abnormality 9.6 DCX NODAL SHH
16 cleft palate, isolated 9.4 ALX3 BMP4 MSX1
17 septopreoptic holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
18 midline interhemispheric variant of holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
19 alobar holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
20 lobar holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
21 microform holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
22 semilobar holoprosencephaly 9.3 FGF8 GLI2 NODAL SHH
23 tooth size 9.2 BMP4 FGF8 MSX1 SHH
24 microphthalmia 9.2 BMP4 GLI2 OTX2 SHH
25 orofacial cleft 8.5 ALX3 BMP4 FGF8 MSX1 NODAL SHH
26 physical disorder 7.9 BMP4 DCX FGF8 MSX1 NODAL SHH

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:

57
Head And Neck Mouth:
cleft palate
microglossia
microstomia
aglossia
hypoplastic oropharynx

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)

Respiratory:
respiratory distress

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:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 narrow mouth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000160
2 microglossia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000171
3 low-set, posteriorly rotated ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000368
4 abnormality of the eye 59 32 Very frequent (99-80%) HP:0000478
5 agenesis of corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0001274
6 abnormality of the cranial nerves 59 32 hallmark (90%) Very frequent (99-80%) HP:0001291
7 holoprosencephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001360
8 polyhydramnios 59 32 hallmark (90%) Very frequent (99-80%) HP:0001561
9 situs inversus totalis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001696
10 respiratory distress 59 32 hallmark (90%) Very frequent (99-80%) HP:0002098
11 aplasia/hypoplasia of the cerebellum 59 32 hallmark (90%) Very frequent (99-80%) HP:0007360
12 hypoplasia of penis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008736
13 cyclopia 59 32 hallmark (90%) Very frequent (99-80%) HP:0009914
14 aplasia/hypoplasia involving the nose 59 32 hallmark (90%) Very frequent (99-80%) HP:0009924
15 mandibular aplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0009939
16 narrow internal auditory canal 59 32 hallmark (90%) Very frequent (99-80%) HP:0011386
17 absent nares 59 32 hallmark (90%) Very frequent (99-80%) HP:0100596
18 synotia 59 32 hallmark (90%) Very frequent (99-80%) HP:0100663
19 aplasia/hypoplasia of the eyebrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0100840
20 cleft palate 32 HP:0000175
21 micrognathia 32 HP:0000347
22 abnormality of the outer ear 32 HP:0000356
23 conductive hearing impairment 32 HP:0000405
24 downslanted palpebral fissures 32 HP:0000494
25 tracheomalacia 32 HP:0002779
26 hypoplasia of the epiglottis 32 HP:0005349
27 laryngeal hypoplasia 32 HP:0008749
28 aglossia 32 HP:0012730

UMLS symptoms related to Agnathia-Otocephaly Complex:


respiratory distress

MGI Mouse Phenotypes related to Agnathia-Otocephaly Complex:

46 (show all 19)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.41 BMP4 CRKL DCX FGF8 GLI2 HHAT
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 BMP4 CRKL DCX
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 SHH FGF8 GLI2 HHAT LBX1 MSX1
9 endocrine/exocrine gland MP:0005379 10.26 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
10 cellular MP:0005384 10.22 OTX1 OTX2 SHH ALX3 BMP4 FGF8
11 homeostasis/metabolism MP:0005376 10.22 NODAL OTX1 OTX2 PRRX1 SHH ALX3
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 NODAL OTX2 PLCB4 SHH BMP4 FGF8
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 GLI2 HHAT MSX1 NODAL OTX2 PGAP1
18 skeleton MP:0005390 9.8 ALX3 BMP4 CRKL FGF8 GLI2 HHAT
19 vision/eye MP:0005391 9.47 FGF8 GLI2 HHAT MSX1 NODAL OTX1

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:

41
Trachea, Cerebellum, Eye

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:

75
# 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 NM_006902.4(PRRX1): c.338T> C (p.Phe113Ser) single nucleotide variant Pathogenic rs387906667 GRCh38 Chromosome 1, 170719822: 170719822
3 PRRX1 PRRX1, ALA231PRO single nucleotide variant Pathogenic
4 PRRX1 NM_006902.4(PRRX1): c.269delA (p.Lys90Argfs) deletion Pathogenic rs398122375 GRCh37 Chromosome 1, 170688894: 170688894
5 PRRX1 NM_006902.4(PRRX1): c.269delA (p.Lys90Argfs) deletion Pathogenic rs398122375 GRCh38 Chromosome 1, 170719753: 170719753
6 PRRX1 NM_006902.4(PRRX1): c.266_269dupAAAA (p.Arg92Glufs) duplication Pathogenic rs398122376 GRCh37 Chromosome 1, 170688891: 170688894
7 PRRX1 NM_006902.4(PRRX1): c.266_269dupAAAA (p.Arg92Glufs) duplication Pathogenic rs398122376 GRCh38 Chromosome 1, 170719750: 170719753

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 86)
# Name GO ID Score Top Affiliating Genes
1 kidney development GO:0001822 9.93 BMP4 FGF8 GLI2 SHH
2 BMP signaling pathway GO:0030509 9.92 BMP4 FGF8 MSX1 NODAL
3 roof of mouth development GO:0060021 9.9 MSX1 PRRX1 SHH
4 determination of left/right symmetry GO:0007368 9.9 FGF8 NODAL SHH
5 cartilage development GO:0051216 9.9 BMP4 MSX1 PRRX1
6 inner ear morphogenesis GO:0042472 9.9 FGF8 OTX1 PRRX1
7 cell development GO:0048468 9.89 BMP4 NODAL SHH
8 smoothened signaling pathway GO:0007224 9.88 BMP4 GLI2 HHAT SHH
9 embryonic skeletal system morphogenesis GO:0048704 9.87 ALX3 BMP4 PRRX1
10 positive regulation of cell differentiation GO:0045597 9.87 BMP4 FGF8 SHH
11 cell fate commitment GO:0045165 9.87 BMP4 FGF8 NODAL SHH
12 branching involved in ureteric bud morphogenesis GO:0001658 9.85 BMP4 FGF8 SHH
13 embryonic digit morphogenesis GO:0042733 9.85 BMP4 GLI2 MSX1 SHH
14 metanephros development GO:0001656 9.84 BMP4 FGF8 SHH
15 protein localization to nucleus GO:0034504 9.84 BMP4 MSX1 SHH
16 heart looping GO:0001947 9.84 FGF8 LBX1 NODAL SHH
17 embryonic forelimb morphogenesis GO:0035115 9.83 ALX3 MSX1 SHH
18 pituitary gland development GO:0021983 9.83 BMP4 GLI2 MSX1
19 branching morphogenesis of an epithelial tube GO:0048754 9.83 BMP4 GLI2 SHH
20 odontogenesis of dentin-containing tooth GO:0042475 9.83 BMP4 GLI2 MSX1 SHH
21 neuron fate commitment GO:0048663 9.82 BMP4 LBX1 SHH
22 embryonic pattern specification GO:0009880 9.81 NODAL PGAP1 SHH
23 embryonic limb morphogenesis GO:0030326 9.81 BMP4 MSX1 PRRX1 SHH
24 vasculature development GO:0001944 9.8 BMP4 NODAL SHH
25 dopaminergic neuron differentiation GO:0071542 9.8 FGF8 OTX2 SHH
26 pattern specification process GO:0007389 9.8 ALX3 CRKL GLI2 SHH
27 lung development GO:0030324 9.8 BMP4 FGF8 GLI2 NODAL SHH
28 heart development GO:0007507 9.8 BMP4 CRKL FGF8 GLI2 MSX1 NODAL
29 lung morphogenesis GO:0060425 9.79 BMP4 FGF8 SHH
30 spinal cord motor neuron differentiation GO:0021522 9.78 GLI2 LBX1 SHH
31 midbrain development GO:0030901 9.78 MSX1 OTX1 OTX2 SHH
32 anterior/posterior axis specification GO:0009948 9.77 BMP4 NODAL PGAP1
33 positive regulation of mesenchymal cell proliferation GO:0002053 9.76 PRRX1 SHH
34 thyroid gland development GO:0030878 9.76 FGF8 SHH
35 outflow tract septum morphogenesis GO:0003148 9.76 BMP4 FGF8
36 renal system development GO:0072001 9.76 BMP4 SHH
37 regulation of smoothened signaling pathway GO:0008589 9.76 GLI2 OTX2
38 hindbrain development GO:0030902 9.76 GLI2 SHH
39 embryonic heart tube development GO:0035050 9.76 FGF8 NODAL
40 dorsal/ventral neural tube patterning GO:0021904 9.76 BMP4 GLI2 SHH
41 odontogenesis GO:0042476 9.76 BMP4 FGF8 MSX1 SHH
42 middle ear morphogenesis GO:0042474 9.75 MSX1 PRRX1
43 signal transduction involved in regulation of gene expression GO:0023019 9.75 FGF8 MSX1
44 male genitalia development GO:0030539 9.75 FGF8 SHH
45 osteoblast development GO:0002076 9.75 GLI2 SHH
46 negative regulation of chondrocyte differentiation GO:0032331 9.75 BMP4 GLI2
47 head development GO:0060322 9.75 GLI2 PGAP1
48 prostate gland development GO:0030850 9.75 GLI2 SHH
49 embryonic morphogenesis GO:0048598 9.74 BMP4 SHH
50 epithelial tube branching involved in lung morphogenesis GO:0060441 9.74 BMP4 SHH

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

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.7 ALX3 GLI2 LBX1 MSX1 OTX1 OTX2
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.56 GLI2 OTX1 OTX2 PRRX1
3 sequence-specific DNA binding GO:0043565 9.17 ALX3 GLI2 LBX1 MSX1 OTX1 OTX2
4 morphogen activity GO:0016015 8.96 NODAL SHH

Sources for Agnathia-Otocephaly Complex

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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