OTFCS
MCID: OTF004
MIFTS: 40

Otofaciocervical Syndrome 1 (OTFCS)

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

Aliases & Classifications for Otofaciocervical Syndrome 1

MalaCards integrated aliases for Otofaciocervical Syndrome 1:

Name: Otofaciocervical Syndrome 1 57 72 29 6 70
Otofaciocervical Syndrome 57 20 58 29 13 39 70
Ofc Syndrome 58 36
Otfcs 57 72
Ofc1 57 72
Ofc 57 72
Oto-Facio-Cervical Syndrome 72
Fara Chlupackova Syndrome 70
Fara-Chlupackova Syndrome 58
Orofacial Cleft 1 70
Ofc; Ofc1 57
Otfcs1 72

Characteristics:

OMIM®:

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

Miscellaneous:
caused by a contiguous gene deletion involving the eya1 gene
one patient has been reported with a heterozygous mutation in eya1


HPO:

31
otofaciocervical syndrome 1:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 166780
OMIM Phenotypic Series 57 PS166780
KEGG 36 H02046
MeSH 44 D000015
ICD10 via Orphanet 33 Q87.0
UMLS via Orphanet 71 C1833691 C2931416
Orphanet 58 ORPHA2792
UMLS 70 C1833691 C1861537 C2931416 more

Summaries for Otofaciocervical Syndrome 1

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2792 Definition Otofaciocervical syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated.

MalaCards based summary : Otofaciocervical Syndrome 1, also known as otofaciocervical syndrome, is related to fara chlupackova syndrome and orofacial cleft 1. An important gene associated with Otofaciocervical Syndrome 1 is EYA1 (EYA Transcriptional Coactivator And Phosphatase 1). The drugs Fentanyl and Narcotics have been mentioned in the context of this disorder. Affiliated tissues include thymus, and related phenotypes are intellectual disability and hyperreflexia

OMIM® : 57 Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability (summary by Pohl et al., 2013). (166780) (Updated 05-Apr-2021)

KEGG : 36 Otofaciocervical syndrome (OFC) is an inherited disorder characterized by facial dysmorphism, external ear anomalies and hearing impairment, branchial cysts or fistulas, anomalies of the vertebrae and the shoulder girdle, and mild intellectual disability. OFC1, inherited as an autosomal dominant trait, is caused by mutations in the EYA1 gene. And OFC2, inherited as an autosomal recessive trait, is caused by mutations in the PAX1 gene.

UniProtKB/Swiss-Prot : 72 Otofaciocervical syndrome 1: A disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability.

Related Diseases for Otofaciocervical Syndrome 1

Graphical network of the top 20 diseases related to Otofaciocervical Syndrome 1:



Diseases related to Otofaciocervical Syndrome 1

Symptoms & Phenotypes for Otofaciocervical Syndrome 1

Human phenotypes related to Otofaciocervical Syndrome 1:

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001347
3 neurological speech impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002167
4 high palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0000218
5 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
6 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
7 macrotia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000400
8 anteverted nares 58 31 hallmark (90%) Very frequent (99-80%) HP:0000463
9 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
10 hypertonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001276
11 full cheeks 58 31 hallmark (90%) Very frequent (99-80%) HP:0000293
12 abnormal dermatoglyphics 58 31 hallmark (90%) Very frequent (99-80%) HP:0007477
13 scapular winging 58 31 hallmark (90%) Very frequent (99-80%) HP:0003691
14 conductive hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000405
15 protruding ear 58 31 hallmark (90%) Very frequent (99-80%) HP:0000411
16 down-sloping shoulders 58 31 hallmark (90%) Very frequent (99-80%) HP:0200021
17 preauricular pit 58 31 hallmark (90%) Very frequent (99-80%) HP:0004467
18 abnormal clavicle morphology 31 hallmark (90%) HP:0000889
19 delayed skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0002750
20 abnormality of the antihelix 58 31 frequent (33%) Frequent (79-30%) HP:0009738
21 renal hypoplasia/aplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008678
22 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
23 atresia of the external auditory canal 58 31 occasional (7.5%) Occasional (29-5%) HP:0000413
24 intellectual disability, mild 31 HP:0001256
25 long face 31 HP:0000276
26 abnormality of the clavicle 58 Very frequent (99-80%)
27 long neck 31 HP:0000472
28 narrow nose 31 HP:0000460

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Face:
narrow face
long face

Head And Neck Mouth:
high-arched palate

Genitourinary Kidneys:
sponge kidneys

Head And Neck Ears:
cochlear malformation
hearing loss, conductive
preauricular pits
prominent ears
dilated inner ear canals
more
Chest Ribs Sternum Clavicles And Scapulae:
sloping shoulders
low-set clavicles
diastasis of the right sternoclavicular joint

Muscle Soft Tissue:
trapezius hypoplasia

Clinical features from OMIM®:

166780 (Updated 05-Apr-2021)

Drugs & Therapeutics for Otofaciocervical Syndrome 1

Drugs for Otofaciocervical Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 3 437-38-7 3345
2 Narcotics Phase 3
3 Anesthetics Phase 3
4 Analgesics, Opioid Phase 3
5 Analgesics Phase 3
6 Anesthetics, Intravenous Phase 3
7 Anesthetics, General Phase 3
8
Sodium citrate Approved, Investigational Phase 2 68-04-2
9
Citric acid Approved, Nutraceutical, Vet_approved Phase 2 77-92-9 311
10 Citrate Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Double-blind, Placebo Controlled Evaluation of the Efficacy, Safety and Tolerability of BEMA™ Fentanyl in the Treatment of Breakthrough Pain in Cancer Subjects Completed NCT00293033 Phase 3 BEMA™;Placebo
2 A 4-week, Open-Label Extension Study of ACTIQ (Oral Transmucosal Fentanyl Citrate [OTFC]) Treatment for Opioid-Tolerant Children and Adolescents With Breakthrough Pain Completed NCT00236093 Phase 2 ACTIQ (Oral Transmucosal Fentanyl Citrate [OTFC])
3 A Double-Blind, Placebo-Comparison Study to Evaluate the Efficacy and Safety of ACTIQ® (Oral Transmucosal Fentanyl Citrate [OTFC®]) Treatment for Opioid-Tolerant Children and Adolescents With Breakthrough Pain Completed NCT00236041 Phase 2 ACTIQ®

Search NIH Clinical Center for Otofaciocervical Syndrome 1

Genetic Tests for Otofaciocervical Syndrome 1

Genetic tests related to Otofaciocervical Syndrome 1:

# Genetic test Affiliating Genes
1 Otofaciocervical Syndrome 1 29 EYA1
2 Otofaciocervical Syndrome 29

Anatomical Context for Otofaciocervical Syndrome 1

MalaCards organs/tissues related to Otofaciocervical Syndrome 1:

40
Thymus

Publications for Otofaciocervical Syndrome 1

Articles related to Otofaciocervical Syndrome 1:

(show all 12)
# Title Authors PMID Year
1
Point mutation of an EYA1-gene splice site in a patient with oto-facio-cervical syndrome. 6 57
16441263 2006
2
A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome. 61 57
23851939 2013
3
Otofaciocervical syndrome: a sporadic patient supports splitting from the branchio-oto-renal syndrome. 57 61
8558563 1995
4
Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM. 57
11409867 2001
5
PAX1 is essential for development and function of the human thymus. 61
32111619 2020
6
T-Cell Immunodeficiencies With Congenital Alterations of Thymic Development: Genes Implicated and Differential Immunological and Clinical Features. 61
32922396 2020
7
Molecular Insights Into the Causes of Human Thymic Hypoplasia With Animal Models. 61
32431714 2020
8
Familial Interstitial 6q23.2 Deletion Including Eya4 Associated With Otofaciocervical Syndrome. 61
31379922 2019
9
Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene. 61
29681087 2018
10
A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency. 61
28657137 2017
11
Generation of Pax1/PAX1-Specific Monoclonal Antibodies. 61
27705080 2016
12
Otofaciocervical syndrome and metachondromatosis in a girl: Presentation of a novel association and remarks on clinical variability of branchial-arch disorders. 61
27240490 2016

Variations for Otofaciocervical Syndrome 1

ClinVar genetic disease variations for Otofaciocervical Syndrome 1:

6 (show top 50) (show all 116)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EYA1 NM_000503.6(EYA1):c.639+1G>A SNV Pathogenic 7942 rs869025180 GRCh37: 8:72211872-72211872
GRCh38: 8:71299637-71299637
2 EYA1 NM_000503.6(EYA1):c.1615G>T (p.Glu539Ter) SNV Likely pathogenic 417930 rs1060499603 GRCh37: 8:72123474-72123474
GRCh38: 8:71211239-71211239
3 EYA1 NM_000503.6(EYA1):c.1748T>C (p.Leu583Pro) SNV Likely pathogenic 48106 rs397517920 GRCh37: 8:72111606-72111606
GRCh38: 8:71199371-71199371
4 EYA1 NM_000503.6(EYA1):c.1460C>T (p.Ser487Leu) SNV Conflicting interpretations of pathogenicity 228678 rs139717960 GRCh37: 8:72127864-72127864
GRCh38: 8:71215629-71215629
5 EYA1 NM_000503.6(EYA1):c.865G>T (p.Asp289Tyr) SNV Conflicting interpretations of pathogenicity 501623 rs201504674 GRCh37: 8:72184094-72184094
GRCh38: 8:71271859-71271859
6 EYA1 NM_000503.6(EYA1):c.-192G>A SNV Uncertain significance 363671 rs886063092 GRCh37: 8:72274019-72274019
GRCh38: 8:71361784-71361784
7 EYA1 NM_000503.6(EYA1):c.827-8T>A SNV Uncertain significance 909567 GRCh37: 8:72184140-72184140
GRCh38: 8:71271905-71271905
8 EYA1 NM_000503.6(EYA1):c.*1229G>A SNV Uncertain significance 910322 GRCh37: 8:72110346-72110346
GRCh38: 8:71198111-71198111
9 EYA1 NM_000503.6(EYA1):c.*1598A>C SNV Uncertain significance 363623 rs886063084 GRCh37: 8:72109977-72109977
GRCh38: 8:71197742-71197742
10 EYA1 NM_000503.6(EYA1):c.*86C>A SNV Uncertain significance 363645 rs186838732 GRCh37: 8:72111489-72111489
GRCh38: 8:71199254-71199254
11 EYA1 NM_000503.6(EYA1):c.-173G>T SNV Uncertain significance 363669 rs886063091 GRCh37: 8:72274000-72274000
GRCh38: 8:71361765-71361765
12 EYA1 NM_000503.6(EYA1):c.1509T>C (p.Thr503=) SNV Uncertain significance 909500 GRCh37: 8:72127710-72127710
GRCh38: 8:71215475-71215475
13 EYA1 NM_000503.6(EYA1):c.1313A>T (p.Tyr438Phe) SNV Uncertain significance 910434 GRCh37: 8:72128974-72128974
GRCh38: 8:71216739-71216739
14 EYA1 NM_000503.6(EYA1):c.-340G>C SNV Uncertain significance 910615 GRCh37: 8:72274167-72274167
GRCh38: 8:71361932-71361932
15 EYA1 NM_000503.6(EYA1):c.*1126T>C SNV Uncertain significance 910323 GRCh37: 8:72110449-72110449
GRCh38: 8:71198214-71198214
16 EYA1 NM_000503.6(EYA1):c.*866C>T SNV Uncertain significance 911535 GRCh37: 8:72110709-72110709
GRCh38: 8:71198474-71198474
17 EYA1 NM_000503.6(EYA1):c.*70G>A SNV Uncertain significance 911601 GRCh37: 8:72111505-72111505
GRCh38: 8:71199270-71199270
18 EYA1 NM_000503.6(EYA1):c.*1561A>G SNV Uncertain significance 908507 GRCh37: 8:72110014-72110014
GRCh38: 8:71197779-71197779
19 EYA1 NM_000503.6(EYA1):c.*1543T>G SNV Uncertain significance 908508 GRCh37: 8:72110032-72110032
GRCh38: 8:71197797-71197797
20 EYA1 NM_000503.6(EYA1):c.*1529C>T SNV Uncertain significance 908509 GRCh37: 8:72110046-72110046
GRCh38: 8:71197811-71197811
21 EYA1 NM_000503.6(EYA1):c.*1391G>A SNV Uncertain significance 908510 GRCh37: 8:72110184-72110184
GRCh38: 8:71197949-71197949
22 EYA1 NM_000503.6(EYA1):c.*755A>T SNV Uncertain significance 908580 GRCh37: 8:72110820-72110820
GRCh38: 8:71198585-71198585
23 EYA1 NM_000503.6(EYA1):c.378G>A (p.Thr126=) SNV Uncertain significance 908770 GRCh37: 8:72234009-72234009
GRCh38: 8:71321774-71321774
24 EYA1 NM_000503.6(EYA1):c.-188C>T SNV Uncertain significance 908831 GRCh37: 8:72274015-72274015
GRCh38: 8:71361780-71361780
25 EYA1 NM_000503.6(EYA1):c.*1297A>G SNV Uncertain significance 909358 GRCh37: 8:72110278-72110278
GRCh38: 8:71198043-71198043
26 EYA1 NM_000503.6(EYA1):c.*1284C>A SNV Uncertain significance 909359 GRCh37: 8:72110291-72110291
GRCh38: 8:71198056-71198056
27 EYA1 NM_000503.6(EYA1):c.*451C>T SNV Uncertain significance 909438 GRCh37: 8:72111124-72111124
GRCh38: 8:71198889-71198889
28 EYA1 NM_000503.6(EYA1):c.*429T>C SNV Uncertain significance 909439 GRCh37: 8:72111146-72111146
GRCh38: 8:71198911-71198911
29 EYA1 NM_000503.6(EYA1):c.1698+14G>A SNV Uncertain significance 908646 GRCh37: 8:72123377-72123377
GRCh38: 8:71211142-71211142
30 EYA1 NM_000503.6(EYA1):c.-155G>A SNV Uncertain significance 363668 rs886063090 GRCh37: 8:72273982-72273982
GRCh38: 8:71361747-71361747
31 EYA1 NM_000503.6(EYA1):c.*442G>A SNV Uncertain significance 363642 rs767388665 GRCh37: 8:72111133-72111133
GRCh38: 8:71198898-71198898
32 EYA1 NM_172059.5(EYA1):c.34-5646_34-5645del Deletion Uncertain significance 363681 rs35320129 GRCh37: 8:72274391-72274392
GRCh38: 8:71362156-71362157
33 EYA1 NM_172059.5(EYA1):c.34-5670C>A SNV Uncertain significance 363683 rs886063099 GRCh37: 8:72274416-72274416
GRCh38: 8:71362181-71362181
34 EYA1 NM_000503.6(EYA1):c.*901dup Duplication Uncertain significance 363634 rs570995924 GRCh37: 8:72110673-72110674
GRCh38: 8:71198438-71198439
35 EYA1 NM_172059.5(EYA1):c.34-5671C>A SNV Uncertain significance 363684 rs886063100 GRCh37: 8:72274417-72274417
GRCh38: 8:71362182-71362182
36 EYA1 NM_000503.6(EYA1):c.*770_*773dup Duplication Uncertain significance 363638 rs371488223 GRCh37: 8:72110801-72110802
GRCh38: 8:71198566-71198567
37 EYA1 NM_000503.6(EYA1):c.*1135_*1138dup Duplication Uncertain significance 363633 rs886063085 GRCh37: 8:72110436-72110437
GRCh38: 8:71198201-71198202
38 EYA1 NM_172059.5(EYA1):c.34-5644_34-5643del Deletion Uncertain significance 363680 rs886063096 GRCh37: 8:72274389-72274390
GRCh38: 8:71362154-71362155
39 EYA1 NM_172059.5(EYA1):c.34-5669_34-5668dup Duplication Uncertain significance 363682 rs35320129 GRCh37: 8:72274390-72274391
GRCh38: 8:71362155-71362156
40 EYA1 NM_000503.6(EYA1):c.*1372_*1375dup Duplication Uncertain significance 363626 rs142792208 GRCh37: 8:72110199-72110200
GRCh38: 8:71197964-71197965
41 EYA1 NM_172059.5(EYA1):c.34-5589A>G SNV Uncertain significance 363679 rs886063095 GRCh37: 8:72274335-72274335
GRCh38: 8:71362100-71362100
42 EYA1 NM_000503.6(EYA1):c.9G>A (p.Met3Ile) SNV Uncertain significance 930620 GRCh37: 8:72267132-72267132
GRCh38: 8:71354897-71354897
43 EYA1 NM_000503.6(EYA1):c.203C>G (p.Ala68Gly) SNV Uncertain significance 930754 GRCh37: 8:72234503-72234503
GRCh38: 8:71322268-71322268
44 EYA1 NM_000503.6(EYA1):c.35G>A (p.Arg12His) SNV Uncertain significance 667048 rs74720958 GRCh37: 8:72267106-72267106
GRCh38: 8:71354871-71354871
45 EYA1 NM_000503.6(EYA1):c.*848G>A SNV Uncertain significance 363635 rs775498240 GRCh37: 8:72110727-72110727
GRCh38: 8:71198492-71198492
46 EYA1 NM_000503.6(EYA1):c.196G>T (p.Gly66Cys) SNV Uncertain significance 363663 rs886063089 GRCh37: 8:72246338-72246338
GRCh38: 8:71334103-71334103
47 EYA1 NM_000503.6(EYA1):c.*117G>A SNV Uncertain significance 363644 rs886063087 GRCh37: 8:72111458-72111458
GRCh38: 8:71199223-71199223
48 EYA1 NM_000503.6(EYA1):c.*1672T>A SNV Uncertain significance 363622 rs777991930 GRCh37: 8:72109903-72109903
GRCh38: 8:71197668-71197668
49 EYA1 NM_000503.6(EYA1):c.*1275G>A SNV Uncertain significance 363629 rs192113669 GRCh37: 8:72110300-72110300
GRCh38: 8:71198065-71198065
50 EYA1 NM_000503.6(EYA1):c.-263C>T SNV Uncertain significance 363673 rs146081509 GRCh37: 8:72274090-72274090
GRCh38: 8:71361855-71361855

Expression for Otofaciocervical Syndrome 1

Search GEO for disease gene expression data for Otofaciocervical Syndrome 1.

Pathways for Otofaciocervical Syndrome 1

GO Terms for Otofaciocervical Syndrome 1

Biological processes related to Otofaciocervical Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anatomical structure development GO:0048856 8.96 PAX1 EYA1
2 pattern specification process GO:0007389 8.62 PAX1 EYA1

Sources for Otofaciocervical Syndrome 1

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
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44 MeSH
45 MESH via Orphanet
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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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