ARCND2
MCID: ARC011
MIFTS: 28

Auriculocondylar Syndrome 2 (ARCND2)

Categories: Ear diseases, Genetic diseases

Aliases & Classifications for Auriculocondylar Syndrome 2

MalaCards integrated aliases for Auriculocondylar Syndrome 2:

Name: Auriculocondylar Syndrome 2 57 72 29 13 6 70
Arcnd2 57 72
Auriculocondylar Syndrome, Type 2 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable phenotype within families


HPO:

31
auriculocondylar syndrome 2:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



Summaries for Auriculocondylar Syndrome 2

OMIM® : 57 Auriculocondylar syndrome (ARCND), also known as 'question-mark ear syndrome' or 'dysgnathia complex,' is an autosomal dominant craniofacial malformation syndrome characterized by highly variable mandibular anomalies, including mild to severe micrognathia, often with temporomandibular joint ankylosis, cleft palate, and a distinctive ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark. Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia (summary by Rieder et al., 2012). For a discussion of genetic heterogeneity of auriculocondylar syndrome, see ARCND1 (602483). (614669) (Updated 05-Apr-2021)

MalaCards based summary : Auriculocondylar Syndrome 2, also known as arcnd2, is related to saethre-chotzen syndrome and auriculo-condylar syndrome, and has symptoms including snoring An important gene associated with Auriculocondylar Syndrome 2 is PLCB4 (Phospholipase C Beta 4). Related phenotypes are macrocephaly and narrow mouth

UniProtKB/Swiss-Prot : 72 Auriculocondylar syndrome 2: A craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.

Related Diseases for Auriculocondylar Syndrome 2

Diseases in the Auriculocondylar Syndrome 1 family:

Auriculocondylar Syndrome 2 Auriculocondylar Syndrome 3

Diseases related to Auriculocondylar Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 saethre-chotzen syndrome 10.1
2 auriculo-condylar syndrome 10.0
3 dysgnathia complex 10.0

Symptoms & Phenotypes for Auriculocondylar Syndrome 2

Human phenotypes related to Auriculocondylar Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 very rare (1%) HP:0000256
2 narrow mouth 31 very rare (1%) HP:0000160
3 glossoptosis 31 very rare (1%) HP:0000162
4 dental malocclusion 31 HP:0000689
5 cleft palate 31 HP:0000175
6 low-set ears 31 HP:0000369
7 dental crowding 31 HP:0000678
8 apnea 31 HP:0002104
9 round face 31 HP:0000311
10 posteriorly rotated ears 31 HP:0000358
11 hypoplastic superior helix 31 HP:0008559
12 overfolding of the superior helices 31 HP:0004453
13 speech articulation difficulties 31 HP:0009088
14 mandibular condyle hypoplasia 31 HP:0007628
15 ankylosis 31 HP:0031013
16 snoring 31 HP:0025267
17 mandibular condyle aplasia 31 HP:0007627
18 cleft at the superior portion of the pinna 31 HP:0008537

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Mouth:
cleft palate
speech articulation difficulties
microstomia (52%)
glossoptosis (46%)
abnormal palate (63%)
more
Head And Neck Ears:
low-set ears
posteriorly rotated ears
overfolding of the superior helices
cleft at the superior portion of the pinna
malformed ears
more
Respiratory:
snoring
respiratory difficulties due to orofacial malformations (36%)
apnea, obstructive
apnea, central (in some patients)

Head And Neck Head:
macrocephaly (25%)

Head And Neck Face:
micrognathia
prominent cheeks
round facial appearance

Skeletal Skull:
short mandibular rami
mandibular condyle hypoplasia
mandibular condyle aplasia
mandibular agenesis
asymmetric mandible
more
Head And Neck Teeth:
malocclusion
crowded teeth
open anterior bite
posterior crossbite

Clinical features from OMIM®:

614669 (Updated 05-Apr-2021)

UMLS symptoms related to Auriculocondylar Syndrome 2:


snoring

Drugs & Therapeutics for Auriculocondylar Syndrome 2

Search Clinical Trials , NIH Clinical Center for Auriculocondylar Syndrome 2

Genetic Tests for Auriculocondylar Syndrome 2

Genetic tests related to Auriculocondylar Syndrome 2:

# Genetic test Affiliating Genes
1 Auriculocondylar Syndrome 2 29 PLCB4

Anatomical Context for Auriculocondylar Syndrome 2

Publications for Auriculocondylar Syndrome 2

Articles related to Auriculocondylar Syndrome 2:

(show all 11)
# Title Authors PMID Year
1
Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. 6 57
23315542 2013
2
A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. 6 57
22560091 2012
3
The question mark ear in patients with mandibular hypoplasia. 6 57
22286465 2012
4
Autosomal dominant isolated question mark ear. 6 57
18680186 2008
5
[Dysgnathia complex, a rare deviation]. 6 57
18686566 2008
6
Question mark ears and post-auricular tags. 57 6
18314001 2008
7
Auriculo-condylar syndrome is associated with highly variable ear and mandibular defects in multiple kindreds. 6 57
16114046 2005
8
Novel features in auriculo-condylar syndrome. 57
20733479 2011
9
Elements of morphology: standard terminology for the ear. 6
19152421 2009
10
A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1. 61
33723370 2021
11
A familial PLCB4 mutation causing auriculocondylar syndrome 2 with variable severity. 61
32201334 2020

Variations for Auriculocondylar Syndrome 2

ClinVar genetic disease variations for Auriculocondylar Syndrome 2:

6 (show top 50) (show all 114)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PLCB4 NM_000933.3(PLCB4):c.1868A>G (p.Tyr623Cys) SNV Pathogenic 31637 rs397514480 GRCh37: 20:9389733-9389733
GRCh38: 20:9409086-9409086
2 PLCB4 NM_000933.3(PLCB4):c.986A>G (p.Asn329Ser) SNV Pathogenic 31638 rs387907179 GRCh37: 20:9364980-9364980
GRCh38: 20:9384333-9384333
3 PLCB4 NM_000933.3(PLCB4):c.1862G>A (p.Arg621His) SNV Pathogenic 31639 rs397514481 GRCh37: 20:9389727-9389727
GRCh38: 20:9409080-9409080
4 PLCB4 NM_000933.3(PLCB4):c.1861C>T (p.Arg621Cys) SNV Pathogenic 31640 rs397514482 GRCh37: 20:9389726-9389726
GRCh38: 20:9409079-9409079
5 PLCB4 NM_000933.3(PLCB4):c.1948A>C (p.Asn650His) SNV Pathogenic 31641 rs397514483 GRCh37: 20:9389813-9389813
GRCh38: 20:9409166-9409166
6 PLCB4 NM_000933.3(PLCB4):c.1862G>T (p.Arg621Leu) SNV Pathogenic 64692 rs397514481 GRCh37: 20:9389727-9389727
GRCh38: 20:9409080-9409080
7 PLCB4 NM_000933.3(PLCB4):c.1073A>T (p.Glu358Val) SNV Pathogenic 64693 rs397514769 GRCh37: 20:9368118-9368118
GRCh38: 20:9387471-9387471
8 PLCB4 NM_000933.3(PLCB4):c.1078G>A (p.Asp360Asn) SNV Pathogenic 64694 rs397514770 GRCh37: 20:9368123-9368123
GRCh38: 20:9387476-9387476
9 PLCB4 NM_000933.3(PLCB4):c.1079A>T (p.Asp360Val) SNV Pathogenic 64695 rs397514771 GRCh37: 20:9368124-9368124
GRCh38: 20:9387477-9387477
10 PLCB4 nsv1067900 Deletion Pathogenic 64696 GRCh37: 20:9388282-9393278
GRCh38: 20:9407635-9412631
11 PLCB4 NM_000933.3(PLCB4):c.1888G>A (p.Asp630Asn) SNV Likely pathogenic 635078 rs1568763104 GRCh37: 20:9389753-9389753
GRCh38: 20:9409106-9409106
12 PLCB4 NM_001377142.1(PLCB4):c.1124A>G (p.His375Arg) SNV Likely pathogenic 1030923 GRCh37: 20:9368169-9368169
GRCh38: 20:9387522-9387522
13 PLCB4 NM_001377142.1(PLCB4):c.2000-5G>T SNV Uncertain significance 898854 GRCh37: 20:9391679-9391679
GRCh38: 20:9411032-9411032
14 PLCB4 NM_001377142.1(PLCB4):c.2030T>A (p.Phe677Tyr) SNV Uncertain significance 898855 GRCh37: 20:9391714-9391714
GRCh38: 20:9411067-9411067
15 PLCB4 NM_001377142.1(PLCB4):c.*109T>C SNV Uncertain significance 898912 GRCh37: 20:9459765-9459765
GRCh38: 20:9479118-9479118
16 PLCB4 NM_001377142.1(PLCB4):c.*343T>G SNV Uncertain significance 898913 GRCh37: 20:9459999-9459999
GRCh38: 20:9479352-9479352
17 PLCB4 NM_001377142.1(PLCB4):c.*1355G>T SNV Uncertain significance 898991 GRCh37: 20:9461011-9461011
GRCh38: 20:9480364-9480364
18 PLCB4 NM_001377142.1(PLCB4):c.*1402A>G SNV Uncertain significance 898992 GRCh37: 20:9461058-9461058
GRCh38: 20:9480411-9480411
19 PLCB4 NM_001377142.1(PLCB4):c.*1412C>T SNV Uncertain significance 898993 GRCh37: 20:9461068-9461068
GRCh38: 20:9480421-9480421
20 PLCB4 NM_001377142.1(PLCB4):c.*1610G>A SNV Uncertain significance 898994 GRCh37: 20:9461266-9461266
GRCh38: 20:9480619-9480619
21 PLCB4 NM_001377142.1(PLCB4):c.591T>A (p.Asp197Glu) SNV Uncertain significance 931883 GRCh37: 20:9352955-9352955
GRCh38: 20:9372308-9372308
22 PLCB4 NM_000933.3(PLCB4):c.3544C>T (p.Gln1182Ter) SNV Uncertain significance 631880 rs1568928967 GRCh37: 20:9459615-9459615
GRCh38: 20:9478968-9478968
23 PLCB4 NM_001377142.1(PLCB4):c.2808G>A (p.Gln936=) SNV Uncertain significance 896168 GRCh37: 20:9424671-9424671
GRCh38: 20:9444024-9444024
24 PLCB4 NM_001377142.1(PLCB4):c.2894T>C (p.Met965Thr) SNV Uncertain significance 896169 GRCh37: 20:9434007-9434007
GRCh38: 20:9453360-9453360
25 PLCB4 NM_001377142.1(PLCB4):c.*874A>G SNV Uncertain significance 896234 GRCh37: 20:9460530-9460530
GRCh38: 20:9479883-9479883
26 PLCB4 NM_001377142.1(PLCB4):c.*1018T>C SNV Uncertain significance 896235 GRCh37: 20:9460674-9460674
GRCh38: 20:9480027-9480027
27 PLCB4 NM_001377142.1(PLCB4):c.*1047C>G SNV Uncertain significance 896236 GRCh37: 20:9460703-9460703
GRCh38: 20:9480056-9480056
28 PLCB4 NM_001377142.1(PLCB4):c.1874+8T>C SNV Uncertain significance 897693 GRCh37: 20:9389372-9389372
GRCh38: 20:9408725-9408725
29 PLCB4 NM_001377142.1(PLCB4):c.1875-3C>T SNV Uncertain significance 897694 GRCh37: 20:9389701-9389701
GRCh38: 20:9409054-9409054
30 PLCB4 NM_001377142.1(PLCB4):c.*1191T>G SNV Uncertain significance 897841 GRCh37: 20:9460847-9460847
GRCh38: 20:9480200-9480200
31 PLCB4 NM_001377142.1(PLCB4):c.*1220A>G SNV Uncertain significance 897842 GRCh37: 20:9460876-9460876
GRCh38: 20:9480229-9480229
32 PLCB4 NM_001377142.1(PLCB4):c.*1292G>A SNV Uncertain significance 897843 GRCh37: 20:9460948-9460948
GRCh38: 20:9480301-9480301
33 PLCB4 NM_001377142.1(PLCB4):c.*1305T>A SNV Uncertain significance 897844 GRCh37: 20:9460961-9460961
GRCh38: 20:9480314-9480314
34 PLCB4 NM_001377142.1(PLCB4):c.84+6G>T SNV Uncertain significance 898788 GRCh37: 20:9288551-9288551
GRCh38: 20:9307904-9307904
35 PLCB4 NM_000933.3(PLCB4):c.1612-11T>G SNV Uncertain significance 339566 rs886056982 GRCh37: 20:9388553-9388553
GRCh38: 20:9407906-9407906
36 PLCB4 NM_000933.3(PLCB4):c.*1011A>G SNV Uncertain significance 339609 rs866488779 GRCh37: 20:9460667-9460667
GRCh38: 20:9480020-9480020
37 PLCB4 NM_000933.3(PLCB4):c.*869G>T SNV Uncertain significance 339606 rs886056987 GRCh37: 20:9460525-9460525
GRCh38: 20:9479878-9479878
38 PLCB4 NM_000933.3(PLCB4):c.*1353A>C SNV Uncertain significance 339612 rs192145916 GRCh37: 20:9461009-9461009
GRCh38: 20:9480362-9480362
39 PLCB4 NM_000933.3(PLCB4):c.2599A>T (p.Ser867Cys) SNV Uncertain significance 339581 rs886056983 GRCh37: 20:9417670-9417670
GRCh38: 20:9437023-9437023
40 PLCB4 NM_000933.3(PLCB4):c.854-13C>T SNV Uncertain significance 339558 rs867987334 GRCh37: 20:9364835-9364835
GRCh38: 20:9384188-9384188
41 PLCB4 NM_000933.3(PLCB4):c.*1461A>G SNV Uncertain significance 339613 rs886056989 GRCh37: 20:9461117-9461117
GRCh38: 20:9480470-9480470
42 PLCB4 NM_000933.3(PLCB4):c.*1104G>T SNV Uncertain significance 339610 rs886056988 GRCh37: 20:9460760-9460760
GRCh38: 20:9480113-9480113
43 PLCB4 NM_000933.3(PLCB4):c.*64T>A SNV Uncertain significance 339596 rs372023385 GRCh37: 20:9459720-9459720
GRCh38: 20:9479073-9479073
44 PLCB4 NM_000933.3(PLCB4):c.854-12T>A SNV Uncertain significance 339559 rs886056981 GRCh37: 20:9364836-9364836
GRCh38: 20:9384189-9384189
45 PLCB4 NM_000933.3(PLCB4):c.535G>A (p.Glu179Lys) SNV Uncertain significance 339556 rs886056980 GRCh37: 20:9351892-9351892
GRCh38: 20:9371245-9371245
46 PLCB4 NM_001377142.1(PLCB4):c.751C>A (p.Arg251=) SNV Uncertain significance 895823 GRCh37: 20:9360707-9360707
GRCh38: 20:9380060-9380060
47 PLCB4 NM_001377142.1(PLCB4):c.2257C>T (p.Arg753Cys) SNV Uncertain significance 895889 GRCh37: 20:9402046-9402046
GRCh38: 20:9421399-9421399
48 PLCB4 NM_001377142.1(PLCB4):c.*470C>A SNV Uncertain significance 895954 GRCh37: 20:9460126-9460126
GRCh38: 20:9479479-9479479
49 PLCB4 NM_001377142.1(PLCB4):c.*586C>T SNV Uncertain significance 895955 GRCh37: 20:9460242-9460242
GRCh38: 20:9479595-9479595
50 PLCB4 NM_001377142.1(PLCB4):c.*694C>T SNV Uncertain significance 895956 GRCh37: 20:9460350-9460350
GRCh38: 20:9479703-9479703

UniProtKB/Swiss-Prot genetic disease variations for Auriculocondylar Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 PLCB4 p.Asn329Thr VAR_068559 rs387907179
2 PLCB4 p.Arg621Cys VAR_068560 rs397514482
3 PLCB4 p.Arg621His VAR_068561 rs397514481
4 PLCB4 p.Tyr623Cys VAR_068562 rs397514480
5 PLCB4 p.Asn650His VAR_068563 rs397514483

Expression for Auriculocondylar Syndrome 2

Search GEO for disease gene expression data for Auriculocondylar Syndrome 2.

Pathways for Auriculocondylar Syndrome 2

GO Terms for Auriculocondylar Syndrome 2

Sources for Auriculocondylar Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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