MCID: ARC008
MIFTS: 43

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 53 25 72
Auriculocondylar Syndrome 53 25 59 37 29 6
Dysgnathia Complex 25 72
Ears Prominent and Constricted 53
Question-Mark Ear Syndrome 25
Question Mark Ear Syndrome 59
Question Mark Ear 53

Characteristics:

Orphanet epidemiological data:

59
auriculocondylar syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

KEGG 37 H01884
MESH via Orphanet 45 C538270
ICD10 via Orphanet 34 Q75.8
UMLS via Orphanet 73 C1865295
Orphanet 59 ORPHA137888
UMLS 72 C1865295 C1876185

Summaries for Auriculo-Condylar Syndrome

Genetics Home Reference : 25 Auriculo-condylar syndrome is a condition that affects facial development, particularly development of the ears and lower jaw (mandible). Most people with auriculo-condylar syndrome have malformed outer ears ("auriculo-" refers to the ears). A hallmark of this condition is an ear abnormality called a "question-mark ear," in which the ears have a distinctive question-mark shape caused by a split that separates the upper part of the ear from the earlobe. Other ear abnormalities that can occur in auriculo-condylar syndrome include cupped ears, ears with fewer folds and grooves than usual (described as "simple"), narrow ear canals, small skin tags in front of or behind the ears, and ears that are rotated backward. Some affected individuals also have hearing loss. Abnormalities of the mandible are another characteristic feature of auriculo-condylar syndrome. These abnormalities often include an unusually small chin (micrognathia) and malfunction of the temporomandibular joint (TMJ), which connects the lower jaw to the skull. Problems with the TMJ affect how the upper and lower jaws fit together and can make it difficult to open and close the mouth. The term "condylar" in the name of the condition refers to the mandibular condyle, which is the upper portion of the mandible that forms part of the TMJ. Other features of auriculo-condylar syndrome can include prominent cheeks, an unusually small mouth (microstomia), differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry), and an opening in the roof of the mouth (cleft palate). These features vary, even among affected members of the same family.

MalaCards based summary : Auriculo-Condylar Syndrome, also known as auriculocondylar syndrome, is related to auriculocondylar syndrome 1 and ankylosis, 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, bone and tongue, and related phenotypes are external ear malformation and mandibular condyle hypoplasia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137888DefinitionA rare disorder that 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.

KEGG : 37
Auriculocondylar syndrome (ACS) is a rare craniofacial malformation syndrome characterized by mandibular hypoplasia and question-mark ears (QME). QMEs, consisting of a specific defect at the lobe-helix junction, can also occur as an isolated anomaly. Studies have indicated the essential role of endothelin 1 (EDN1) signaling through the endothelin receptor type A (EDNRA) in patterning the mandibular portion of the first pharyngeal arch. Mutations in the PLCB4 and GNAI3, predicted to function as signal transducers downstream of EDNRA, have recently been reported in ACS.

Related Diseases for Auriculo-Condylar Syndrome

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:

59 32 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 external ear malformation 59 32 hallmark (90%) Very frequent (99-80%) HP:0008572
2 mandibular condyle hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0007628
3 cleft helix 59 32 hallmark (90%) Very frequent (99-80%) HP:0009902
4 dental malocclusion 59 32 frequent (33%) Frequent (79-30%) HP:0000689
5 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
6 glossoptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000162
7 cleft palate 59 32 frequent (33%) Frequent (79-30%) HP:0000175
8 respiratory distress 59 32 frequent (33%) Frequent (79-30%) HP:0002098
9 narrow mouth 59 32 frequent (33%) Frequent (79-30%) HP:0000160
10 low-set, posteriorly rotated ears 59 32 frequent (33%) Frequent (79-30%) HP:0000368
11 facial asymmetry 59 32 frequent (33%) Frequent (79-30%) HP:0000324
12 preauricular skin tag 59 32 frequent (33%) Frequent (79-30%) HP:0000384
13 dental crowding 59 32 frequent (33%) Frequent (79-30%) HP:0000678
14 obstructive sleep apnea 59 32 frequent (33%) Frequent (79-30%) HP:0002870
15 abnormality of the temporomandibular joint 59 32 frequent (33%) Frequent (79-30%) HP:0010754
16 bifid uvula 59 32 frequent (33%) Frequent (79-30%) HP:0000193
17 difficulty in tongue movements 59 32 frequent (33%) Frequent (79-30%) HP:0000183
18 aplasia/hypoplasia of the external ear 59 32 frequent (33%) Frequent (79-30%) HP:0008772
19 abnormality of the crus of the helix 59 32 frequent (33%) Frequent (79-30%) HP:0009895
20 snoring 59 32 frequent (33%) Frequent (79-30%) HP:0025267
21 question mark ear 59 32 frequent (33%) Frequent (79-30%) HP:0030022
22 periauricular skin pits 59 32 frequent (33%) Frequent (79-30%) HP:0100277
23 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
24 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
25 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
26 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
27 generalized hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001290
28 feeding difficulties 59 32 occasional (7.5%) Occasional (29-5%) HP:0011968
29 microglossia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000171
30 mandibular condyle aplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0007627
31 hamartoma of tongue 59 32 occasional (7.5%) Occasional (29-5%) HP:0011802
32 vein of galen aneurysmal malformation 59 32 very rare (1%) Very rare (<4-1%) HP:0030713
33 micrognathia 59 Frequent (79-30%)
34 abnormality of the pinna 59 Frequent (79-30%)

UMLS symptoms related to Auriculo-Condylar Syndrome:


apnea, snoring

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 29

Anatomical Context for Auriculo-Condylar Syndrome

MalaCards organs/tissues related to Auriculo-Condylar Syndrome:

41
Skin, Bone, Tongue

Publications for Auriculo-Condylar Syndrome

Articles related to Auriculo-Condylar Syndrome:

(show all 34)
# Title Authors PMID Year
1
Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears. 38 71
24268655 2013
2
Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. 38 71
23315542 2013
3
A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. 38 71
22560091 2012
4
Autosomal dominant isolated question mark ear. 38 71
18680186 2008
5
Question mark ears and post-auricular tags. 38 71
18314001 2008
6
Auriculo-condylar syndrome is associated with highly variable ear and mandibular defects in multiple kindreds. 38 71
16114046 2005
7
Auriculo-condylar syndrome: additional patients. 38 71
12244558 2002
8
The question mark ear in patients with mandibular hypoplasia. 71
22286465 2012
9
Elements of morphology: standard terminology for the ear. 71
19152421 2009
10
[Dysgnathia complex, a rare deviation]. 71
18686566 2008
11
Transmission of the dysgnathia complex from mother to daughter. 71
11102934 2000
12
The association of severe encephalopathy and question mark ear is highly suggestive of loss of MEF2C function. 38
28456137 2018
13
Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome. 38
28328130 2017
14
Respiratory and gastrointestinal dysfunctions associated with auriculo-condylar syndrome and a homozygous PLCB4 loss-of-function mutation. 38
27007857 2016
15
Dominant-negative Gα subunits are a mechanism of dysregulated heterotrimeric G protein signaling in human disease. 38
27072656 2016
16
Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development. 38
27880803 2016
17
The Partnership of Medical Genetics and Oral and Maxillofacial Surgery When Evaluating Craniofacial Anomalies. 38
26608141 2015
18
Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect. 38
25026904 2015
19
A mouse splice-site mutant and individuals with atypical chromosome 22q11.2 deletions demonstrate the crucial role for crkl in craniofacial and pharyngeal development. 38
25565927 2014
20
Clinical evidence for a mandibular to maxillary transformation in Auriculocondylar syndrome. 38
24677549 2014
21
Understanding the basis of auriculocondylar syndrome: Insights from human, mouse and zebrafish genetic studies. 38
24123988 2013
22
Further characterization of atypical features in auriculocondylar syndrome caused by recessive PLCB4 mutations. 38
23913798 2013
23
Ossicular fusion and cholesteatoma in auriculo-condylar syndrome: in vivo evidence of arrest of embryogenesis. 38
22865651 2013
24
Auriculo-condylar syndrome. 38
22050072 2012
25
Auriculo-condylar syndrome. Confronting a diagnostic challenge. 38
22105959 2012
26
Novel features in auriculo-condylar syndrome. 38
20733479 2011
27
Syndromes of the first and second pharyngeal arches: A review. 38
19610085 2009
28
Evaluation of molar teeth and buds in patients submitted to mandible distraction: long-term results. 38
18349653 2008
29
Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity. 38
18000524 2008
30
Microtia, severe micrognathia and absent ossicles: auriculo-condylar syndrome or new entity? 38
17159508 2007
31
The correction of auricular and mandibular deformities in auriculo-condylar syndrome. 38
15915123 2005
32
Auriculo-condylar syndrome or new syndrome? 38
12002148 2002
33
Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity? 38
11045585 2000
34
Auriculo-condylar syndrome: further evidence for a new disorder. 38
10449647 1999

Variations for Auriculo-Condylar Syndrome

ClinVar genetic disease variations for Auriculo-Condylar Syndrome:

6 (show top 50) (show all 67)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PLCB4 NM_001172646.1(PLCB4): c.833A> T (p.Asp278Val) single nucleotide variant Conflicting interpretations of pathogenicity rs147655952 20:9360789-9360789 20:9380142-9380142
2 PLCB4 NM_001172646.1(PLCB4): c.2566A> G (p.Ile856Val) single nucleotide variant Uncertain significance rs151284195 20:9416248-9416248 20:9435601-9435601
3 PLCB4 NM_001172646.1(PLCB4): c.1611+12C> T single nucleotide variant Uncertain significance rs761137370 20:9382249-9382249 20:9401602-9401602
4 PLCB4 NM_001172646.1(PLCB4): c.3408+11T> C single nucleotide variant Uncertain significance rs762636208 20:9453505-9453505 20:9472858-9472858
5 PLCB4 NM_001172646.1(PLCB4): c.*489G> T single nucleotide variant Uncertain significance rs886056986 20:9460125-9460125 20:9479478-9479478
6 PLCB4 NM_001172646.1(PLCB4): c.*889G> T single nucleotide variant Uncertain significance rs886056987 20:9460525-9460525 20:9479878-9479878
7 PLCB4 NM_001172646.1(PLCB4): c.1749C> T (p.Tyr583=) single nucleotide variant Uncertain significance rs149835904 20:9388665-9388665 20:9408018-9408018
8 PLCB4 NM_001172646.1(PLCB4): c.854-12T> A single nucleotide variant Uncertain significance rs886056981 20:9364836-9364836 20:9384189-9384189
9 PLCB4 NM_001172646.1(PLCB4): c.1648-11T> G single nucleotide variant Uncertain significance rs886056982 20:9388553-9388553 20:9407906-9407906
10 PLCB4 NM_001172646.1(PLCB4): c.1738A> G (p.Met580Val) single nucleotide variant Uncertain significance rs369233949 20:9388654-9388654 20:9408007-9408007
11 PLCB4 NM_001172646.1(PLCB4): c.*84T> A single nucleotide variant Uncertain significance rs372023385 20:9459720-9459720 20:9479073-9479073
12 PLCB4 NM_001172646.1(PLCB4): c.*1124G> T single nucleotide variant Uncertain significance rs886056988 20:9460760-9460760 20:9480113-9480113
13 PLCB4 NM_001172646.1(PLCB4): c.*1373A> C single nucleotide variant Uncertain significance rs192145916 20:9461009-9461009 20:9480362-9480362
14 PLCB4 NM_001172646.1(PLCB4): c.226-8C> T single nucleotide variant Uncertain significance rs78678483 20:9319533-9319533 20:9338886-9338886
15 PLCB4 NM_001172646.1(PLCB4): c.854-13C> T single nucleotide variant Uncertain significance rs867987334 20:9364835-9364835 20:9384188-9384188
16 PLCB4 NM_001172646.1(PLCB4): c.1833C> T (p.Val611=) single nucleotide variant Uncertain significance rs778436381 20:9389323-9389323 20:9408676-9408676
17 PLCB4 NM_001172646.1(PLCB4): c.2635A> T (p.Ser879Cys) single nucleotide variant Uncertain significance rs886056983 20:9417670-9417670 20:9437023-9437023
18 PLCB4 NM_001172646.1(PLCB4): c.3409-4del deletion Uncertain significance rs886056984 20:9453922-9453922 20:9473275-9473275
19 PLCB4 NM_000933.3(PLCB4): c.3460-5_3460-2delAACA deletion Uncertain significance rs886056985 20:9457359-9457362 20:9476712-9476715
20 PLCB4 NM_001172646.1(PLCB4): c.*1031A> G single nucleotide variant Uncertain significance rs866488779 20:9460667-9460667 20:9480020-9480020
21 PLCB4 NM_001172646.1(PLCB4): c.*1481A> G single nucleotide variant Uncertain significance rs886056989 20:9461117-9461117 20:9480470-9480470
22 PLCB4 NM_001172646.1(PLCB4): c.*1692del deletion Uncertain significance rs886056991 20:9461328-9461328 20:9480681-9480681
23 PLCB4 NM_001172646.1(PLCB4): c.535G> A (p.Glu179Lys) single nucleotide variant Uncertain significance rs886056980 20:9351892-9351892 20:9371245-9371245
24 PLCB4 NM_001172646.1(PLCB4): c.1462T> G (p.Ser488Ala) single nucleotide variant Likely benign rs185740474 20:9376217-9376217 20:9395570-9395570
25 PLCB4 NM_001172646.1(PLCB4): c.3497C> T (p.Ala1166Val) single nucleotide variant Likely benign rs145676690 20:9459569-9459569 20:9478922-9478922
26 PLCB4 NM_001172646.1(PLCB4): c.2858C> A (p.Ser953Tyr) single nucleotide variant Likely benign rs148347249 20:9424868-9424868 20:9444221-9444221
27 PLCB4 NM_001172646.1(PLCB4): c.3119T> C (p.Ile1040Thr) single nucleotide variant Likely benign rs530143044 20:9440328-9440328 20:9459681-9459681
28 PLCB4 NM_001172646.1(PLCB4): c.3122A> G (p.Asn1041Ser) single nucleotide variant Likely benign rs147312767 20:9440331-9440331 20:9459684-9459684
29 PLCB4 NM_001172646.1(PLCB4): c.1885C> T (p.Arg629Trp) single nucleotide variant Likely benign rs530479821 20:9389714-9389714 20:9409067-9409067
30 PLCB4 NM_001172646.1(PLCB4): c.504-6C> T single nucleotide variant Likely benign rs184366128 20:9351855-9351855 20:9371208-9371208
31 PLCB4 NM_001172646.1(PLCB4): c.1485C> T (p.Asp495=) single nucleotide variant Likely benign rs374048213 20:9376240-9376240 20:9395593-9395593
32 PLCB4 NM_001172646.1(PLCB4): c.462G> A (p.Leu154=) single nucleotide variant Likely benign rs142392531 20:9346120-9346120 20:9365473-9365473
33 PLCB4 NM_001172646.1(PLCB4): c.*1786G> A single nucleotide variant Likely benign rs189786768 20:9461422-9461422 20:9480775-9480775
34 PLCB4 NM_001172646.1(PLCB4): c.2052-7C> T single nucleotide variant Likely benign rs185396159 20:9400447-9400447 20:9419800-9419800
35 PLCB4 NM_001172646.1(PLCB4): c.2154+9C> G single nucleotide variant Likely benign rs199598049 20:9400565-9400565 20:9419918-9419918
36 PLCB4 NM_001172646.1(PLCB4): c.2331G> C (p.Pro777=) single nucleotide variant Likely benign rs147575829 20:9404406-9404406 20:9423759-9423759
37 PLCB4 NM_001172646.1(PLCB4): c.*1507G> C single nucleotide variant Likely benign rs546587344 20:9461143-9461143 20:9480496-9480496
38 PLCB4 NM_001172646.1(PLCB4): c.*1222G> A single nucleotide variant Likely benign rs114009007 20:9460858-9460858 20:9480211-9480211
39 PLCB4 NM_001172646.1(PLCB4): c.*1751A> T single nucleotide variant Likely benign rs147197006 20:9461387-9461387 20:9480740-9480740
40 PLCB4 NM_001172646.1(PLCB4): c.*583del deletion Likely benign rs148015873 20:9460219-9460219 20:9479572-9479572
41 PLCB4 NM_001172646.1(PLCB4): c.*394A> G single nucleotide variant Likely benign rs138221578 20:9460030-9460030 20:9479383-9479383
42 PLCB4 NM_001172646.1(PLCB4): c.*758G> A single nucleotide variant Likely benign rs41275612 20:9460394-9460394 20:9479747-9479747
43 PLCB4 NM_001172646.1(PLCB4): c.*1605dup duplication Likely benign rs565091978 20:9461241-9461241 20:9480594-9480594
44 PLCB4 NM_001172646.1(PLCB4): c.2525-8T> C single nucleotide variant Likely benign rs185755472 20:9416199-9416199 20:9435552-9435552
45 PLCB4 NM_001172646.1(PLCB4): c.2628C> T (p.Asp876=) single nucleotide variant Likely benign rs35218589 20:9417663-9417663 20:9437016-9437016
46 PLCB4 NM_001172646.1(PLCB4): c.2936A> G (p.Gln979Arg) single nucleotide variant Likely benign rs141568926 20:9434049-9434049 20:9453402-9453402
47 PLCB4 NM_001172646.1(PLCB4): c.2997-6T> C single nucleotide variant Likely benign rs117123647 20:9438055-9438055 20:9457408-9457408
48 PLCB4 NM_001172646.1(PLCB4): c.3028A> G (p.Thr1010Ala) single nucleotide variant Likely benign rs377357771 20:9438092-9438092 20:9457445-9457445
49 PLCB4 NM_001172646.1(PLCB4): c.*110A> T single nucleotide variant Likely benign rs554019512 20:9459746-9459746 20:9479099-9479099
50 PLCB4 NM_001172646.1(PLCB4): c.*229A> C single nucleotide variant Likely benign rs576484180 20:9459865-9459865 20:9479218-9479218

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 PLCB4 GNAI3 EDN1
2
Show member pathways
12.41 PLCB4 GNAI3 EDN1
3
Show member pathways
12.34 PLCB4 GNAI3 EDN1
4
Show member pathways
12.14 PLCB4 GNAI3
5
Show member pathways
12.12 PLCB4 GNAI3
6
Show member pathways
12.07 PLCB4 GNAI3 EDN1
7 12.01 PLCB4 GNAI3
8 11.95 PLCB4 GNAI3
9
Show member pathways
11.92 PLCB4 GNAI3
10
Show member pathways
11.79 PLCB4 GNAI3
11
Show member pathways
11.72 PLCB4 GNAI3 EDN1
12 11.69 PLCB4 GNAI3
13 11.64 PLCB4 GNAI3
14 11.61 PLCB4 GNAI3
15
Show member pathways
11.56 PLCB4 GNAI3
16 11.56 PLCB4 GNAI3
17 11.55 PLCB4 GNAI3
18
Show member pathways
11.54 PLCB4 GNAI3
19 11.5 PLCB4 GNAI3
20 11.5 PLCB4 GNAI3
21 11.46 PLCB4 EDN1
22 11.38 PLCB4 GNAI3
23 11.16 PLCB4 GNAI3
24 11.03 PLCB4 GNAI3
25 10.99 PLCB4 GNAI3
26 10.87 PLCB4 GNAI3
27 10.07 PLCB4 GNAI3

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 PLCB4 GNAI3 EDN1
2 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway GO:0007193 8.96 GNAI3 EDN1
3 positive regulation of vascular smooth muscle cell proliferation GO:1904707 8.62 GNAI3 EDN1

Sources for Auriculo-Condylar Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
Content
Loading form....