MCID: BRN003
MIFTS: 53

Branchiooculofacial Syndrome malady

Genetic diseases, Rare diseases, Fetal diseases categories

Aliases & Classifications for Branchiooculofacial Syndrome

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Sources:
49OMIM, 10Disease Ontology, 11diseasecard, 21GeneReviews, 45NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 47Novoseek, 12DISEASES, 51Orphanet, 24GTR, 65UMLS, 67UniProtKB/Swiss-Prot, 28ICD10 via Orphanet, 66UMLS via Orphanet, 34MedGen, 36MeSH
See all sources

Aliases & Descriptions for Branchiooculofacial Syndrome:

Name: Branchiooculofacial Syndrome 49 10 11 21 45 22 12 24 67
Branchio-Oculo-Facial Syndrome 22 23 47 51 65 67
Hemangiomatous Branchial Clefts-Lip Pseudocleft Syndrome 45 23 67
Bof Syndrome 21 47 67
Bofs 23 51 67
 
Branchial Clefts with Characteristic Facies Growth Retardation Imperforate Nasolacrimal Duct and Premature Aging 45 67
Lip Pseudocleft-Hemangiomatous Branchial Cyst Syndrome 45 67
Bofs Syndrome 45 22
Branchial Clefts with Characteristic Facies, Growth Retardation, Imperforate Nasolacrimal Duct, and Premature Aging 23
Lip Pseudocleft-Hemagiomatous Branchial Cyst Syndrome 23


Classifications:



Characteristics (Orphanet epidemiological data):

51
branchio-oculo-facial syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal


External Ids:

OMIM49 113620
Disease Ontology10 DOID:0050691
Orphanet51 1297
ICD10 via Orphanet28 Q18.8
UMLS via Orphanet66 C0376524
MedGen34 C0376524
MeSH36 D019280

Summaries for Branchiooculofacial Syndrome

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OMIM:49 Branchiooculofacial syndrome (BOFS) is characterized by branchial cleft sinus defects, ocular anomalies such as... (113620) more...

MalaCards based summary: Branchiooculofacial Syndrome, also known as branchio-oculo-facial syndrome, is related to burn-mckeown syndrome and polydactyly, and has symptoms including everted lower lip vermilion, low-set, posteriorly rotated ears and conductive hearing impairment. An important gene associated with Branchiooculofacial Syndrome is TFAP2A (Transcription Factor AP-2 Alpha (Activating Enhancer Binding Protein 2 Alpha)), and among its related pathways is Neural Crest Differentiation. Affiliated tissues include skin, eye and kidney, and related mouse phenotypes are renal/urinary system and limbs/digits/tail.

Disease Ontology:10 An autosomal dominant disease that is characterized by low birth weight and growth retardation, bilateral branchial clefts.

Genetics Home Reference:23 Branchio-oculo-facial syndrome is a condition that affects development before birth, particularly of structures in the face and neck. Its characteristic features include skin anomalies on the neck, malformations of the eyes and ears, and distinctive facial features.

NIH Rare Diseases:45 Branchiooculofacial syndrome (bofs) is a very rare genetic disorder that is apparent at birth. only about 50 cases of bofs had been reported in the medical literature. like its name implies, bofs is characterized by skin defects, eye abnormalities, and distinctive facial features. among the reported cases thus far, the symptoms may vary from mild to severe. bofs is caused by mutations in the tfap2a gene and inherited as an autosomal dominant trait. last updated: 6/23/2011

UniProtKB/Swiss-Prot:67 Branchiooculofacial syndrome: A syndrome characterized by growth retardation, bilateral branchial sinus defects with hemangiomatous, scarred skin, cleft lip with or without cleft palate, pseudocleft of the upper lip, nasolacrimal duct obstruction, low set ears with posterior rotation, a malformed, asymmetrical nose with a broad bridge and flattened tip, conductive or sensorineural deafness, ocular and renal anomalies.

GeneReviews summary for bofs

Related Diseases for Branchiooculofacial Syndrome

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

(show all 28)
idRelated DiseaseScoreTop Affiliating Genes
1burn-mckeown syndrome10.4
2polydactyly10.4
3microphthalmia10.4
4pulmonic stenosis10.4
5cardiomyopathy10.4
6colobomatous microphthalmia10.4
7c9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia10.3EYA1, SIX5
8ectopic thymus10.2
9tooth agenesis, selective, 210.2EYA1, SALL1
10van maldergem syndrome10.2EYA1, SIX5
11schimke immunoosseous dysplasia10.2IRF6, TBX22
12renal hypodysplasia/aplasia 110.1EYA1, SALL1, SIX5
13focal dermal hypoplasia10.1
14ectodermal dysplasia10.1
15renal tubular dysgenesis, ace-related10.1EYA1, SALL1
16familial isolated arrhythmogenic ventricular dysplasia, left dominant form10.1DSP, PKP2
17liver carcinoma in situ10.1MSX1, TBX22
18right temporal lobar atrophy10.1DSP, PKP2
19mitf-related melanoma and renal cell carcinoma predisposition syndrome10.1DSP, PKP2
20arrhythmogenic right ventricular dysplasia 1210.0DSP, PKP2
21middle lobe syndrome10.0DACH1, EYA1, SALL1, SIX5
22bacterial esophagitis9.9EYA1, SIX5, TFAP2A, TP63
23adult syndrome9.8PKP2, TP63
24bladder tubulo-cystic clear cell adenocarcinoma9.6BMP4, IRF6, MSX1, TFAP2A, TP63
25orofaciodigital syndrome9.6BMP4, IRF6, MSX1, TBX22, TP63
26myasthenic syndrome, congenital, 2a, slow-channel9.6BMP4, IRF6, MSX1, TBX22, TP63
27asphyxiating thoracic dystrophy9.5BMP4, DSP, IRF6, MSX1, TP63
28branchiooculofacial syndrome7.9ATP8B1, BMP4, DACH1, DSP, EYA1, GDF3

Graphical network of the top 20 diseases related to Branchiooculofacial Syndrome:



Diseases related to branchiooculofacial syndrome

Symptoms for Branchiooculofacial Syndrome

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Symptoms by clinical synopsis from OMIM:

113620

Clinical features from OMIM:

113620

Symptoms:

 51 (show all 37)
  • retinoschisis/retinal/chorioretinal coloboma
  • protruding lips
  • philtrum deeply grooved
  • external ear anomalies
  • low set ears/posteriorly rotated ears
  • branchial/posterior auricular/preauricular/cheek cysts/fistulae
  • conductive deafness/hearing loss
  • skin hypoplasia/aplasia/atrophy
  • dermoid sinus/dimple/pit (excluding sacral)
  • capillary hemangioma/nevus/naevus flammeus/port-wine stain
  • autosomal dominant inheritance
  • dolichocephaly/scaphocephaly
  • upslanted palpebral fissures/mongoloid slanting palpebral fissures
  • coloboma of iris
  • defect/anomaly of lacrimal system
  • broad nose/nasal bridge
  • short columella/depressed nasal tip
  • lateral cleft lip/gingival cleft/paramedian nasal cleft
  • high vaulted/narrow palate
  • complete/partial microdontia
  • anodontia/oligodontia/hypodontia
  • premature greying of hair
  • dysplastic/thick/grooved fingernails
  • abnormal cry/voice/phonation disorder/nasal speech
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • short stature/dwarfism/nanism
  • intrauterine growth retardation
  • microcornea
  • cataract/lens opacification
  • strabismus/squint
  • ptosis
  • lip pits/fistulae
  • cleft lip and palate
  • preaxial polydactyly (hand)
  • agenesis/hypoplasia/aplasia of kidneys
  • multicystic kidney/renal dysplasia
  • megaureter/hydronephrosis/pyeloureteral junction syndrome

HPO human phenotypes related to Branchiooculofacial Syndrome:

(show all 102)
id Description Frequency HPO Source Accession
1 everted lower lip vermilion hallmark (90%) HP:0000232
2 low-set, posteriorly rotated ears hallmark (90%) HP:0000368
3 conductive hearing impairment hallmark (90%) HP:0000405
4 chorioretinal coloboma hallmark (90%) HP:0000567
5 deep philtrum hallmark (90%) HP:0002002
6 aplasia/hypoplasia of the skin hallmark (90%) HP:0008065
7 external ear malformation hallmark (90%) HP:0008572
8 sacrococcygeal pilonidal abnormality hallmark (90%) HP:0010767
9 abnormality of the palate typical (50%) HP:0000174
10 dolichocephaly typical (50%) HP:0000268
11 abnormality of the nose typical (50%) HP:0000366
12 upslanted palpebral fissure typical (50%) HP:0000582
13 iris coloboma typical (50%) HP:0000612
14 lacrimation abnormality typical (50%) HP:0000632
15 microdontia typical (50%) HP:0000691
16 abnormality of the fingernails typical (50%) HP:0001231
17 intrauterine growth retardation typical (50%) HP:0001511
18 abnormality of the voice typical (50%) HP:0001608
19 neurological speech impairment typical (50%) HP:0002167
20 premature graying of hair typical (50%) HP:0002216
21 short stature typical (50%) HP:0004322
22 postnatal growth retardation typical (50%) HP:0008897
23 reduced number of teeth typical (50%) HP:0009804
24 non-midline cleft lip typical (50%) HP:0100335
25 multicystic kidney dysplasia occasional (7.5%) HP:0000003
26 microcornea occasional (7.5%) HP:0000482
27 strabismus occasional (7.5%) HP:0000486
28 ptosis occasional (7.5%) HP:0000508
29 cataract occasional (7.5%) HP:0000518
30 preaxial hand polydactyly occasional (7.5%) HP:0001177
31 renal hypoplasia/aplasia occasional (7.5%) HP:0008678
32 lip pit occasional (7.5%) HP:0100267
33 autosomal dominant inheritance HP:0000006
34 cryptorchidism HP:0000028
35 hypospadias HP:0000047
36 renal agenesis HP:0000104
37 renal cyst HP:0000107
38 abnormality of the teeth HP:0000164
39 cleft palate HP:0000175
40 lower lip pit HP:0000196
41 cleft upper lip HP:0000204
42 microcephaly HP:0000252
43 dolichocephaly HP:0000268
44 malar flattening HP:0000272
45 hypertelorism HP:0000316
46 micrognathia HP:0000347
47 small forehead HP:0000350
48 low-set ears HP:0000369
49 overfolded helix HP:0000396
50 conductive hearing impairment HP:0000405
51 sensorineural hearing impairment HP:0000407
52 short nasal septum HP:0000420
53 broad nasal tip HP:0000455
54 short neck HP:0000470
55 retinal coloboma HP:0000480
56 strabismus HP:0000486
57 telecanthus HP:0000506
58 ptosis HP:0000508
59 cataract HP:0000518
60 anophthalmia HP:0000528
61 myopia HP:0000545
62 microphthalmos HP:0000568
63 nasolacrimal duct obstruction HP:0000579
64 upslanted palpebral fissure HP:0000582
65 iris coloboma HP:0000612
66 nystagmus HP:0000639
67 single transverse palmar crease HP:0000954
68 atypical scarring of skin HP:0000987
69 aplasia cutis congenita HP:0001057
70 preaxial hand polydactyly HP:0001177
71 seizures HP:0001250
72 intellectual disability, mild HP:0001256
73 intrauterine growth retardation HP:0001511
74 nasal speech HP:0001611
75 hypoplastic fingernail HP:0001804
76 gastroesophageal reflux HP:0002020
77 pyloric stenosis HP:0002021
78 low posterior hairline HP:0002162
79 white forelock HP:0002211
80 premature graying of hair HP:0002216
81 agenesis of cerebellar vermis HP:0002335
82 supernumerary nipple HP:0002558
83 kyphosis HP:0002808
84 elbow flexion contracture HP:0002987
85 hyperlordosis HP:0003307
86 clinodactyly of the 5th finger HP:0004209
87 dermal atrophy HP:0004334
88 postauricular pit HP:0004464
89 preauricular pit HP:0004467
90 malrotation of colon HP:0004785
91 duplication of internal organs HP:0005217
92 depressed nasal bridge HP:0005280
93 fusion of middle ear ossicles HP:0005473
94 wide intermamillary distance HP:0006610
95 microtia HP:0008551
96 hypoplastic superior helix HP:0008559
97 supraauricular pit HP:0008606
98 proximal placement of thumb HP:0009623
99 short thumb HP:0009778
100 branchial anomaly HP:0009794
101 ectopic thymus tissue HP:0010517
102 hamartoma HP:0010566

Drugs & Therapeutics for Branchiooculofacial Syndrome

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Branchiooculofacial Syndrome

Genetic Tests for Branchiooculofacial Syndrome

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Genetic tests related to Branchiooculofacial Syndrome:

id Genetic test Affiliating Genes
1 Branchiooculofacial Syndrome22 24 TFAP2A

Anatomical Context for Branchiooculofacial Syndrome

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MalaCards organs/tissues related to Branchiooculofacial Syndrome:

33
Skin, Eye, Kidney, Thymus, Colon

Animal Models for Branchiooculofacial Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Branchiooculofacial Syndrome:

38 (show all 20)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.0BMP4, EYA1, MAFB, PAX3, SALL1, TP63
2MP:00053717.7BMP4, IRF6, MSX1, PAX3, SALL1, TFAP2A
3MP:00028737.7BMP4, EYA1, GDF3, PAX3, SALL1, TBX22
4MP:00053917.7BMP4, EYA1, MSX1, PAX3, SIX5, TFAP2A
5MP:00053697.6BMP4, EYA1, MSX1, PAX3, PKP2, SIX5
6MP:00053777.4ATP8B1, BMP4, EYA1, IRF6, MAFB, MSX1
7MP:00053827.3BMP4, EYA1, IRF6, MAFB, MSX1, PAX3
8MP:00107717.2BMP4, DSP, IRF6, MSX1, PAX3, TFAP2A
9MP:00053817.2BMP4, EYA1, IRF6, MSX1, PAX3, SALL1
10MP:00053857.0BMP4, EYA1, MAFB, MSX1, PAX3, PKP2
11MP:00053907.0BMP4, EYA1, IRF6, MAFB, MSX1, PAX3
12MP:00053886.9BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
13MP:00053796.8BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
14MP:00036316.8ATP8B1, BMP4, DACH1, EYA1, MAFB, MSX1
15MP:00053866.7BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
16MP:00053806.6BMP4, DSP, EYA1, GDF3, MAFB, MSX1
17MP:00053846.5BMP4, DSP, EYA1, GDF3, IRF6, MAFB
18MP:00053786.3ATP8B1, BMP4, DSP, GDF3, IRF6, MSX1
19MP:00053765.6ATP8B1, BMP4, DACH1, EYA1, GDF3, MAFB
20MP:00107685.3BMP4, DACH1, DSP, EYA1, GDF3, IRF6

Publications for Branchiooculofacial Syndrome

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Articles related to Branchiooculofacial Syndrome:

idTitleAuthorsYear
1
Branchiootorenal and branchiooculofacial syndrome. (25569411)
2015
2
Branchiooculofacial syndrome and bilateral ectopic thymus: report of a family. (23106675)
2012
3
Branchiooculofacial Syndrome (21634087)
1993

Variations for Branchiooculofacial Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Branchiooculofacial Syndrome:

67
id Symbol AA change Variation ID SNP ID
1TFAP2Ap.Leu249ProVAR_045838
2TFAP2Ap.Arg254GlyVAR_045839
3TFAP2Ap.Arg255GlyVAR_045840
4TFAP2Ap.Gly262GluVAR_045841

Clinvar genetic disease variations for Branchiooculofacial Syndrome:

5
id Gene Variation Type Significance SNP ID Assembly Location
1TFAP2ANM_001042425.1(TFAP2A): c.751A> G (p.Arg251Gly)single nucleotide variantPathogenicrs121909574GRCh37Chr 6, 10404742: 10404742
2TFAP2ANM_001042425.1(TFAP2A): c.773G> A (p.Gly258Glu)single nucleotide variantPathogenicrs121909575GRCh37Chr 6, 10402823: 10402823
3TFAP2ATFAP2A, 12-BP DEL, NT697deletionPathogenic
4TFAP2ATFAP2A, PHE319SERsingle nucleotide variantPathogenic
5TFAP2ATFAP2A, 18-BP DEL/6-BP INS, NT828indelPathogenic
6TFAP2ANM_001042425.1(TFAP2A): c.874G> A (p.Glu292Lys)single nucleotide variantPathogenicrs267607108GRCh37Chr 6, 10400820: 10400820
7TFAP2ANM_001042425.1(TFAP2A): c.698G> A (p.Arg233Gln)single nucleotide variantPathogenicrs151344525GRCh37Chr 6, 10404795: 10404795
8TFAP2ANM_001042425.1(TFAP2A): c.637C> A (p.Arg213Ser)single nucleotide variantPathogenicrs793888540GRCh37Chr 6, 10404856: 10404856
9TFAP2ANM_001042425.1(TFAP2A): c.629T> A (p.Val210Asp)single nucleotide variantPathogenicrs793888541GRCh37Chr 6, 10404864: 10404864

Expression for genes affiliated with Branchiooculofacial Syndrome

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Search GEO for disease gene expression data for Branchiooculofacial Syndrome.

Pathways for genes affiliated with Branchiooculofacial Syndrome

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Pathways related to Branchiooculofacial Syndrome according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
18.5BMP4, MSX1, PAX3, TFAP2A

GO Terms for genes affiliated with Branchiooculofacial Syndrome

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Cellular components related to Branchiooculofacial Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1desmosomeGO:00300579.9DSP, PKP2
2nucleusGO:00056345.3DACH1, DSP, EYA1, IRF6, KCTD1, MAFB

Biological processes related to Branchiooculofacial Syndrome according to GeneCards Suite gene sharing:

(show all 40)
idNameGO IDScoreTop Affiliating Genes
1outer ear morphogenesisGO:004247310.6EYA1, SALL1
2middle ear morphogenesisGO:004247410.5EYA1, MSX1
3negative regulation of transcription by competitive promoter bindingGO:001094410.4DACH1, TFAP2A
4regulation of cell fate commitmentGO:001045310.4BMP4, GDF3
5mesenchymal to epithelial transition involved in metanephros morphogenesisGO:000333710.3BMP4, SALL1
6bundle of His cell-Purkinje myocyte adhesion involved in cell communicationGO:008607310.3DSP, PKP2
7regulation of ventricular cardiac muscle cell action potentialGO:009891110.3DSP, PKP2
8bone morphogenesisGO:006034910.3MSX1, TFAP2A
9keratinocyte proliferationGO:004361610.2IRF6, TP63
10pituitary gland developmentGO:002198310.2BMP4, SALL1
11negative regulation of myoblast differentiationGO:004566210.2BMP4, GDF3
12regulation of heart rate by cardiac conductionGO:008609110.2DSP, PKP2
13odontogenesisGO:004247610.1BMP4, MSX1
14embryonic hindlimb morphogenesisGO:003511610.1BMP4, MSX1
15positive regulation of BMP signaling pathwayGO:003051310.0BMP4, MSX1
16smooth muscle tissue developmentGO:004874510.0BMP4, TP63
17cloacal septationGO:006019710.0BMP4, TP63
18anatomical structure formation involved in morphogenesisGO:00486469.9BMP4, TP63
19ureteric bud developmentGO:00016579.9BMP4, EYA1, SALL1
20branching involved in ureteric bud morphogenesisGO:00016589.9BMP4, EYA1, SALL1
21inner ear morphogenesisGO:00424729.9EYA1, MAFB, TFAP2A
22kidney developmentGO:00018229.8BMP4, SALL1, TFAP2A
23neuron fate commitmentGO:00486639.8BMP4, PAX3
24embryonic digit morphogenesisGO:00427339.8BMP4, MSX1, SALL1
25BMP signaling pathwayGO:00305099.6BMP4, GDF3, MSX1
26embryonic limb morphogenesisGO:00303269.4BMP4, MSX1, TP63
27keratinocyte differentiationGO:00302169.4DSP, IRF6, TP63
28odontogenesis of dentin-containing toothGO:00424759.4BMP4, MSX1, TP63
29neural tube closureGO:00018439.3BMP4, PAX3, SALL1
30organ morphogenesisGO:00098879.3EYA1, PAX3, TP63
31skeletal system developmentGO:00015019.2BMP4, GDF3, TP63
32sensory perception of soundGO:00076059.0ATP8B1, EYA1, PAX3, TFAP2A
33negative regulation of cell proliferationGO:00082858.8BMP4, IRF6, MSX1, PKP2, SIX5, TFAP2A
34heart developmentGO:00075078.1BMP4, MSX1, PAX3, PKP2, SALL1
35positive regulation of transcription, DNA-templatedGO:00458938.1BMP4, IRF6, PAX3, SALL1, TFAP2A, TP63
36transcription from RNA polymerase II promoterGO:00063667.8MAFB, MSX1, PAX3, TFAP2A, TP63
37negative regulation of transcription, DNA-templatedGO:00458927.1ATP8B1, BMP4, DACH1, KCTD1, MSX1, SALL1
38negative regulation of transcription from RNA polymerase II promoterGO:00001227.0BMP4, DACH1, MSX1, PAX3, SALL1, TBX22
39positive regulation of transcription from RNA polymerase II promoterGO:00459446.8BMP4, EYA1, MAFB, MSX1, PAX3, SALL1
40regulation of transcription, DNA-templatedGO:00063556.7DACH1, EYA1, IRF6, MAFB, MSX1, PAX3

Molecular functions related to Branchiooculofacial Syndrome according to GeneCards Suite gene sharing:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific bindingGO:000098210.5MSX1, TFAP2A
2cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communicationGO:008608310.4DSP, PKP2
3transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific bindingGO:000107810.2DACH1, SALL1, TFAP2A
4RNA polymerase II core promoter proximal region sequence-specific DNA bindingGO:000097810.0MAFB, SALL1, SIX5, TFAP2A
5chromatin bindingGO:00036828.4PAX3, SALL1, TFAP2A, TP63
6sequence-specific DNA bindingGO:00435657.5MAFB, MSX1, PAX3, SALL1, SIX5, TFAP2A
7DNA bindingGO:00036777.2DACH1, IRF6, MAFB, MSX1, PAX3, SALL1
8transcription factor activity, sequence-specific DNA bindingGO:00037007.0DACH1, IRF6, MAFB, PAX3, SALL1, TBX22
9protein bindingGO:00055154.1ATP8B1, BMP4, DACH1, DSP, EYA1, GDF3

Sources for Branchiooculofacial Syndrome

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet