MCID: ARC008
MIFTS: 40

Auriculo-Condylar Syndrome

Categories: Bone diseases, Ear diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Auriculo-Condylar Syndrome

MalaCards integrated aliases for Auriculo-Condylar Syndrome:

Name: Auriculo-Condylar Syndrome 54 26 74
Auriculocondylar Syndrome 54 26 60 38 30 6
Dysgnathia Complex 26 74
Ears Prominent and Constricted 54
Question-Mark Ear Syndrome 26
Question Mark Ear Syndrome 60
Question Mark Ear 54

Characteristics:

Orphanet epidemiological data:

60
auriculocondylar syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:



Summaries for Auriculo-Condylar Syndrome

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137888Disease definitionAuriculo-condylar syndrome (ACS) presents with bilateral external ear malformations ('question mark' ears), mandibular condyle hypoplasia, microstomia, micrognathia, microglossia and facial asymmetry. Additional manifestations include hypotonia, ptosis, cleft palate, puffy cheeks, developmental delay, impaired hearing and respiratory distress.EpidemiologySo far, ACS has been reported in six multigenerational families.EtiologyThis condition can be classified as a disease of the first and second embryonic pharyngeal arches and is characterized by significant intra- and interfamilial phenotypic variation.Genetic counselingIt is transmitted in an autosomal dominant manner.Visit the Orphanet disease page for more resources.

MalaCards based summary : Auriculo-Condylar Syndrome, also known as auriculocondylar syndrome, is related to auriculocondylar syndrome 1 and agnathia-otocephaly complex, and has symptoms including apnea and snoring. An important gene associated with Auriculo-Condylar Syndrome is PLCB4 (Phospholipase C Beta 4), and among its related pathways/superpathways are PEDF Induced Signaling and Circadian entrainment. Affiliated tissues include skin, tongue and bone, and related phenotypes are external ear malformation and mandibular condyle hypoplasia

Genetics Home Reference : 26 Auriculo-condylar syndrome is a condition that affects facial development, particularly development of the ears and lower jaw (mandible).

Related Diseases for Auriculo-Condylar Syndrome

Diseases related to Auriculo-Condylar Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 auriculocondylar syndrome 1 31.8 GNAI3 PLCB4
2 agnathia-otocephaly complex 11.9
3 dysgnathia complex 11.5
4 microphthalmia, syndromic 5 10.2
5 auriculocondylar syndrome 2 10.2
6 auriculocondylar syndrome 3 10.2
7 cholesteatoma of middle ear 10.2
8 hypotonia 10.2
9 microtia 10.2
10 question mark ears, isolated 10.2
11 holoprosencephaly 10.1
12 encephalopathy 9.9
13 ankylosis 9.6 GNAI3 PLCB4
14 ear malformation 9.3 EDN1 GNAI3 PLCB4

Graphical network of the top 20 diseases related to Auriculo-Condylar Syndrome:



Diseases related to Auriculo-Condylar Syndrome

Symptoms & Phenotypes for Auriculo-Condylar Syndrome

Human phenotypes related to Auriculo-Condylar Syndrome:

60 33 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 external ear malformation 60 33 hallmark (90%) Very frequent (99-80%) HP:0008572
2 mandibular condyle hypoplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0007628
3 cleft helix 60 33 hallmark (90%) Very frequent (99-80%) HP:0009902
4 dental malocclusion 60 33 frequent (33%) Frequent (79-30%) HP:0000689
5 full cheeks 60 33 frequent (33%) Frequent (79-30%) HP:0000293
6 glossoptosis 60 33 frequent (33%) Frequent (79-30%) HP:0000162
7 cleft palate 60 33 frequent (33%) Frequent (79-30%) HP:0000175
8 respiratory distress 60 33 frequent (33%) Frequent (79-30%) HP:0002098
9 low-set, posteriorly rotated ears 60 33 frequent (33%) Frequent (79-30%) HP:0000368
10 dental crowding 60 33 frequent (33%) Frequent (79-30%) HP:0000678
11 narrow mouth 60 33 frequent (33%) Frequent (79-30%) HP:0000160
12 obstructive sleep apnea 60 33 frequent (33%) Frequent (79-30%) HP:0002870
13 preauricular skin tag 60 33 frequent (33%) Frequent (79-30%) HP:0000384
14 facial asymmetry 60 33 frequent (33%) Frequent (79-30%) HP:0000324
15 bifid uvula 60 33 frequent (33%) Frequent (79-30%) HP:0000193
16 difficulty in tongue movements 60 33 frequent (33%) Frequent (79-30%) HP:0000183
17 aplasia/hypoplasia of the external ear 60 33 frequent (33%) Frequent (79-30%) HP:0008772
18 abnormality of the crus of the helix 60 33 frequent (33%) Frequent (79-30%) HP:0009895
19 abnormality of the temporomandibular joint 60 33 frequent (33%) Frequent (79-30%) HP:0010754
20 snoring 60 33 frequent (33%) Frequent (79-30%) HP:0025267
21 question mark ear 60 33 frequent (33%) Frequent (79-30%) HP:0030022
22 periauricular skin pits 60 33 frequent (33%) Frequent (79-30%) HP:0100277
23 macrocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000256
24 ptosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000508
25 hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000365
26 global developmental delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001263
27 feeding difficulties 60 33 occasional (7.5%) Occasional (29-5%) HP:0011968
28 generalized hypotonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001290
29 microglossia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000171
30 mandibular condyle aplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0007627
31 hamartoma of tongue 60 33 occasional (7.5%) Occasional (29-5%) HP:0011802
32 vein of galen aneurysmal malformation 60 33 very rare (1%) Very rare (<4-1%) HP:0030713
33 micrognathia 60 Frequent (79-30%)
34 abnormality of the pinna 60 Frequent (79-30%)

UMLS symptoms related to Auriculo-Condylar Syndrome:


apnea, snoring

GenomeRNAi Phenotypes related to Auriculo-Condylar Syndrome according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.32 PLCB4
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 9.32 PLCB4
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.32 EDN1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.32 EDN1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-211 9.32 PLCB4
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 9.32 PLCB4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-58 9.32 EDN1 PLCB4
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.32 PLCB4
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.32 EDN1

Drugs & Therapeutics for Auriculo-Condylar Syndrome

Search Clinical Trials , NIH Clinical Center for Auriculo-Condylar Syndrome

Genetic Tests for Auriculo-Condylar Syndrome

Genetic tests related to Auriculo-Condylar Syndrome:

# Genetic test Affiliating Genes
1 Auriculocondylar Syndrome 30

Anatomical Context for Auriculo-Condylar Syndrome

MalaCards organs/tissues related to Auriculo-Condylar Syndrome:

42
Skin, Tongue, Bone

Publications for Auriculo-Condylar Syndrome

Articles related to Auriculo-Condylar Syndrome:

(show all 21)
# Title Authors Year
1
Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome. ( 28328130 )
2017
2
Respiratory and gastrointestinal dysfunctions associated with auriculo-condylar syndrome and a homozygous PLCB4 loss-of-function mutation. ( 27007857 )
2016
3
Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect. ( 25026904 )
2015
4
Clinical evidence for a mandibular to maxillary transformation in Auriculocondylar syndrome. ( 24677549 )
2014
5
Ossicular fusion and cholesteatoma in auriculo-condylar syndrome: in vivo evidence of arrest of embryogenesis. ( 22865651 )
2013
6
Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. ( 23315542 )
2013
7
Further characterization of atypical features in auriculocondylar syndrome caused by recessive PLCB4 mutations. ( 23913798 )
2013
8
Understanding the basis of auriculocondylar syndrome: Insights from human, mouse and zebrafish genetic studies. ( 24123988 )
2013
9
Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears. ( 24268655 )
2013
10
Auriculo-condylar syndrome. ( 22050072 )
2012
11
Auriculo-condylar syndrome. Confronting a diagnostic challenge. ( 22105959 )
2012
12
A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. ( 22560091 )
2012
13
Novel features in auriculo-condylar syndrome. ( 20733479 )
2011
14
Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity. ( 18000524 )
2008
15
Microtia, severe micrognathia and absent ossicles: auriculo-condylar syndrome or new entity? ( 17159508 )
2007
16
The correction of auricular and mandibular deformities in auriculo-condylar syndrome. ( 15915123 )
2005
17
Auriculo-condylar syndrome is associated with highly variable ear and mandibular defects in multiple kindreds. ( 16114046 )
2005
18
Auriculo-condylar syndrome or new syndrome? ( 12002148 )
2002
19
Auriculo-condylar syndrome: additional patients. ( 12244558 )
2002
20
Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity? ( 11045585 )
2000
21
Auriculo-condylar syndrome: further evidence for a new disorder. ( 10449647 )
1999

Variations for Auriculo-Condylar Syndrome

ClinVar genetic disease variations for Auriculo-Condylar Syndrome:

6 (show top 50) (show all 134)
# Gene Variation Type Significance SNP ID Assembly Location
1 PLCB4 NM_000933.3(PLCB4): c.2118+8C> A single nucleotide variant Likely benign rs75492366 GRCh37 Chromosome 20, 9400564: 9400564
2 PLCB4 NM_000933.3(PLCB4): c.2364G> A (p.Pro788=) single nucleotide variant Benign rs16995899 GRCh38 Chromosome 20, 9423828: 9423828
3 PLCB4 NM_000933.3(PLCB4): c.833A> T (p.Asp278Val) single nucleotide variant Conflicting interpretations of pathogenicity rs147655952 GRCh37 Chromosome 20, 9360789: 9360789
4 PLCB4 NM_000933.3(PLCB4): c.833A> T (p.Asp278Val) single nucleotide variant Conflicting interpretations of pathogenicity rs147655952 GRCh38 Chromosome 20, 9380142: 9380142
5 PLCB4 NM_000933.3(PLCB4): c.1364A> G (p.Lys455Arg) single nucleotide variant Likely benign rs142617224 GRCh38 Chromosome 20, 9393628: 9393628
6 PLCB4 NM_000933.3(PLCB4): c.1364A> G (p.Lys455Arg) single nucleotide variant Likely benign rs142617224 GRCh37 Chromosome 20, 9374275: 9374275
7 PLCB4 NM_000933.3(PLCB4): c.1428T> C (p.Ala476=) single nucleotide variant Likely benign rs140773788 GRCh38 Chromosome 20, 9395536: 9395536
8 PLCB4 NM_000933.3(PLCB4): c.1428T> C (p.Ala476=) single nucleotide variant Likely benign rs140773788 GRCh37 Chromosome 20, 9376183: 9376183
9 PLCB4 NM_000933.3(PLCB4): c.1713C> T (p.Tyr571=) single nucleotide variant Uncertain significance rs149835904 GRCh38 Chromosome 20, 9408018: 9408018
10 PLCB4 NM_000933.3(PLCB4): c.1713C> T (p.Tyr571=) single nucleotide variant Uncertain significance rs149835904 GRCh37 Chromosome 20, 9388665: 9388665
11 PLCB4 NM_000933.3(PLCB4): c.2118+8C> A single nucleotide variant Likely benign rs75492366 GRCh38 Chromosome 20, 9419917: 9419917
12 PLCB4 NM_000933.3(PLCB4): c.2364G> A (p.Pro788=) single nucleotide variant Benign rs16995899 GRCh37 Chromosome 20, 9404475: 9404475
13 PLCB4 NM_000933.3(PLCB4): c.*209A> C single nucleotide variant Likely benign rs576484180 GRCh37 Chromosome 20, 9459865: 9459865
14 PLCB4 NM_000933.3(PLCB4): c.2530A> G (p.Ile844Val) single nucleotide variant Uncertain significance rs151284195 GRCh38 Chromosome 20, 9435601: 9435601
15 PLCB4 NM_000933.3(PLCB4): c.2530A> G (p.Ile844Val) single nucleotide variant Uncertain significance rs151284195 GRCh37 Chromosome 20, 9416248: 9416248
16 PLCB4 NM_000933.3(PLCB4): c.*90A> T single nucleotide variant Likely benign rs554019512 GRCh37 Chromosome 20, 9459746: 9459746
17 PLCB4 NM_000933.3(PLCB4): c.*90A> T single nucleotide variant Likely benign rs554019512 GRCh38 Chromosome 20, 9479099: 9479099
18 PLCB4 NM_000933.3(PLCB4): c.*209A> C single nucleotide variant Likely benign rs576484180 GRCh38 Chromosome 20, 9479218: 9479218
19 PLCB4 NM_000933.3(PLCB4): c.*230G> C single nucleotide variant Likely benign rs149256309 GRCh37 Chromosome 20, 9459886: 9459886
20 PLCB4 NM_000933.3(PLCB4): c.*230G> C single nucleotide variant Likely benign rs149256309 GRCh38 Chromosome 20, 9479239: 9479239
21 PLCB4 NM_000933.3(PLCB4): c.*271A> G single nucleotide variant Benign rs2076392 GRCh37 Chromosome 20, 9459927: 9459927
22 PLCB4 NM_000933.3(PLCB4): c.*271A> G single nucleotide variant Benign rs2076392 GRCh38 Chromosome 20, 9479280: 9479280
23 PLCB4 NM_000933.3(PLCB4): c.*469G> T single nucleotide variant Uncertain significance rs886056986 GRCh37 Chromosome 20, 9460125: 9460125
24 PLCB4 NM_000933.3(PLCB4): c.*469G> T single nucleotide variant Uncertain significance rs886056986 GRCh38 Chromosome 20, 9479478: 9479478
25 PLCB4 NM_000933.3(PLCB4): c.*563delG deletion Likely benign rs148015873 GRCh38 Chromosome 20, 9479572: 9479572
26 PLCB4 NM_000933.3(PLCB4): c.*563delG deletion Likely benign rs148015873 GRCh37 Chromosome 20, 9460219: 9460219
27 PLCB4 NM_000933.3(PLCB4): c.*869G> T single nucleotide variant Uncertain significance rs886056987 GRCh38 Chromosome 20, 9479878: 9479878
28 PLCB4 NM_000933.3(PLCB4): c.*869G> T single nucleotide variant Uncertain significance rs886056987 GRCh37 Chromosome 20, 9460525: 9460525
29 PLCB4 NM_000933.3(PLCB4): c.*1003A> C single nucleotide variant Benign rs74772813 GRCh38 Chromosome 20, 9480012: 9480012
30 PLCB4 NM_000933.3(PLCB4): c.*1003A> C single nucleotide variant Benign rs74772813 GRCh37 Chromosome 20, 9460659: 9460659
31 PLCB4 NM_000933.3(PLCB4): c.*1202G> A single nucleotide variant Likely benign rs114009007 GRCh38 Chromosome 20, 9480211: 9480211
32 PLCB4 NM_000933.3(PLCB4): c.*1202G> A single nucleotide variant Likely benign rs114009007 GRCh37 Chromosome 20, 9460858: 9460858
33 PLCB4 NM_000933.3(PLCB4): c.*1487G> C single nucleotide variant Likely benign rs546587344 GRCh38 Chromosome 20, 9480496: 9480496
34 PLCB4 NM_000933.3(PLCB4): c.*1487G> C single nucleotide variant Likely benign rs546587344 GRCh37 Chromosome 20, 9461143: 9461143
35 PLCB4 NM_000933.3(PLCB4): c.*1731A> T single nucleotide variant Likely benign rs147197006 GRCh38 Chromosome 20, 9480740: 9480740
36 PLCB4 NM_000933.3(PLCB4): c.*1731A> T single nucleotide variant Likely benign rs147197006 GRCh37 Chromosome 20, 9461387: 9461387
37 PLCB4 NM_000933.3(PLCB4): c.226-8C> T single nucleotide variant Uncertain significance rs78678483 GRCh37 Chromosome 20, 9319533: 9319533
38 PLCB4 NM_000933.3(PLCB4): c.226-8C> T single nucleotide variant Uncertain significance rs78678483 GRCh38 Chromosome 20, 9338886: 9338886
39 PLCB4 NM_000933.3(PLCB4): c.462G> A (p.Leu154=) single nucleotide variant Likely benign rs142392531 GRCh37 Chromosome 20, 9346120: 9346120
40 PLCB4 NM_000933.3(PLCB4): c.462G> A (p.Leu154=) single nucleotide variant Likely benign rs142392531 GRCh38 Chromosome 20, 9365473: 9365473
41 PLCB4 NM_000933.3(PLCB4): c.854-12T> A single nucleotide variant Uncertain significance rs886056981 GRCh38 Chromosome 20, 9384189: 9384189
42 PLCB4 NM_000933.3(PLCB4): c.854-12T> A single nucleotide variant Uncertain significance rs886056981 GRCh37 Chromosome 20, 9364836: 9364836
43 PLCB4 NM_000933.3(PLCB4): c.1612-11T> G single nucleotide variant Uncertain significance rs886056982 GRCh38 Chromosome 20, 9407906: 9407906
44 PLCB4 NM_000933.3(PLCB4): c.1612-11T> G single nucleotide variant Uncertain significance rs886056982 GRCh37 Chromosome 20, 9388553: 9388553
45 PLCB4 NM_000933.3(PLCB4): c.1702A> G (p.Met568Val) single nucleotide variant Uncertain significance rs369233949 GRCh38 Chromosome 20, 9408007: 9408007
46 PLCB4 NM_000933.3(PLCB4): c.1702A> G (p.Met568Val) single nucleotide variant Uncertain significance rs369233949 GRCh37 Chromosome 20, 9388654: 9388654
47 PLCB4 NM_000933.3(PLCB4): c.2016-7C> T single nucleotide variant Likely benign rs185396159 GRCh38 Chromosome 20, 9419800: 9419800
48 PLCB4 NM_000933.3(PLCB4): c.2016-7C> T single nucleotide variant Likely benign rs185396159 GRCh37 Chromosome 20, 9400447: 9400447
49 PLCB4 NM_000933.3(PLCB4): c.2118+9C> G single nucleotide variant Likely benign rs199598049 GRCh38 Chromosome 20, 9419918: 9419918
50 PLCB4 NM_000933.3(PLCB4): c.2118+9C> G single nucleotide variant Likely benign rs199598049 GRCh37 Chromosome 20, 9400565: 9400565

Expression for Auriculo-Condylar Syndrome

Search GEO for disease gene expression data for Auriculo-Condylar Syndrome.

Pathways for Auriculo-Condylar Syndrome

Pathways related to Auriculo-Condylar Syndrome according to GeneCards Suite gene sharing:

(show all 27)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.15 EDN1 GNAI3 PLCB4
2
Show member pathways
12.42 EDN1 GNAI3 PLCB4
3
Show member pathways
12.34 EDN1 GNAI3 PLCB4
4
Show member pathways
12.14 GNAI3 PLCB4
5
Show member pathways
12.12 GNAI3 PLCB4
6
Show member pathways
12.07 EDN1 GNAI3 PLCB4
7 12.01 GNAI3 PLCB4
8 11.95 GNAI3 PLCB4
9
Show member pathways
11.92 GNAI3 PLCB4
10
Show member pathways
11.79 GNAI3 PLCB4
11
Show member pathways
11.72 EDN1 GNAI3 PLCB4
12 11.69 GNAI3 PLCB4
13 11.64 GNAI3 PLCB4
14 11.61 GNAI3 PLCB4
15
Show member pathways
11.56 GNAI3 PLCB4
16 11.56 GNAI3 PLCB4
17 11.55 GNAI3 PLCB4
18
Show member pathways
11.54 GNAI3 PLCB4
19 11.5 GNAI3 PLCB4
20 11.48 GNAI3 PLCB4
21 11.46 EDN1 PLCB4
22 11.38 GNAI3 PLCB4
23 11.16 GNAI3 PLCB4
24 11.03 GNAI3 PLCB4
25 10.99 GNAI3 PLCB4
26 10.89 GNAI3 PLCB4
27 10.07 GNAI3 PLCB4

GO Terms for Auriculo-Condylar Syndrome

Biological processes related to Auriculo-Condylar Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor signaling pathway GO:0007186 9.33 EDN1 GNAI3 PLCB4
2 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway GO:0007193 8.96 EDN1 GNAI3
3 positive regulation of vascular smooth muscle cell proliferation GO:1904707 8.62 EDN1 GNAI3

Sources for Auriculo-Condylar Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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