MCID: BRN003
MIFTS: 51

Branchiooculofacial Syndrome malady

Categories: Genetic diseases, Rare diseases, Fetal diseases

Aliases & Classifications for Branchiooculofacial Syndrome

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Aliases & Descriptions for Branchiooculofacial Syndrome:

Name: Branchiooculofacial Syndrome 50 11 22 46 23 13 68 25 12
Branchio-Oculo-Facial Syndrome 23 24 52 68 48 66
Bof Syndrome 22 23 68 48
Hemangiomatous Branchial Clefts-Lip Pseudocleft Syndrome 46 24 68
Bofs 24 52 68
 
Branchial Clefts with Characteristic Facies Growth Retardation Imperforate Nasolacrimal Duct and Premature Aging 46 68
Lip Pseudocleft-Hemangiomatous Branchial Cyst Syndrome 46 68
Branchial Clefts with Characteristic Facies, Growth Retardation, Imperforate Nasolacrimal Duct, and Premature Aging 24
Lip Pseudocleft-Hemagiomatous Branchial Cyst Syndrome 24
Bofs Syndrome 46

Characteristics:

Orphanet epidemiological data:

52
branchio-oculo-facial syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal

HPO:

62
branchiooculofacial syndrome:
Inheritance: autosomal dominant inheritance


Classifications:



External Ids:

OMIM50 113620
Disease Ontology11 DOID:0050691
Orphanet52 ORPHA1297
ICD10 via Orphanet29 Q18.8
UMLS via Orphanet67 C0376524
MedGen35 C0376524
MeSH37 D019280

Summaries for Branchiooculofacial Syndrome

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OMIM:50 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 cask-related disorders, 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), and among its related pathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Neural Crest Differentiation. Affiliated tissues include skin, eye and thymus, and related mouse phenotypes are renal/urinary system and hearing/vestibular/ear.

Disease Ontology:11 An autosomal dominant disease that is characterized by low birth weight and growth retardation, bilateral branchial clefts.

Genetics Home Reference:24 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:46 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:68 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 NBK55063

Related Diseases for Branchiooculofacial Syndrome

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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:

 52 (show all 37)
  • multicystic kidney dysplasia
  • renal agenesis
  • hydronephrosis
  • oral cleft
  • high palate
  • everted lower lip vermilion
  • dolichocephaly
  • low-set, posteriorly rotated ears
  • abnormality of the pinna
  • conductive hearing impairment
  • wide nasal bridge
  • broad nasal tip
  • microcornea
  • strabismus
  • ptosis
  • cataract
  • nasolacrimal duct obstruction
  • upslanted palpebral fissure
  • coloboma
  • iris coloboma
  • microdontia
  • atypical scarring of skin
  • hemangioma
  • preaxial hand polydactyly
  • intrauterine growth retardation
  • nasal speech
  • deep philtrum
  • neurological speech impairment
  • premature graying of hair
  • short stature
  • postauricular pit
  • preauricular pit
  • supraauricular pit
  • reduced number of teeth
  • upper lip pit
  • non-midline cleft lip
  • fingernail dysplasia

HPO human phenotypes related to Branchiooculofacial Syndrome:

(show all 101)
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 cryptorchidism HP:0000028
34 hypospadias HP:0000047
35 renal agenesis HP:0000104
36 renal cyst HP:0000107
37 abnormality of the teeth HP:0000164
38 cleft palate HP:0000175
39 lower lip pit HP:0000196
40 cleft upper lip HP:0000204
41 microcephaly HP:0000252
42 dolichocephaly HP:0000268
43 malar flattening HP:0000272
44 hypertelorism HP:0000316
45 micrognathia HP:0000347
46 small forehead HP:0000350
47 low-set ears HP:0000369
48 overfolded helix HP:0000396
49 conductive hearing impairment HP:0000405
50 sensorineural hearing impairment HP:0000407
51 short nasal septum HP:0000420
52 broad nasal tip HP:0000455
53 short neck HP:0000470
54 retinal coloboma HP:0000480
55 strabismus HP:0000486
56 telecanthus HP:0000506
57 ptosis HP:0000508
58 cataract HP:0000518
59 anophthalmia HP:0000528
60 myopia HP:0000545
61 microphthalmia HP:0000568
62 nasolacrimal duct obstruction HP:0000579
63 upslanted palpebral fissure HP:0000582
64 iris coloboma HP:0000612
65 nystagmus HP:0000639
66 single transverse palmar crease HP:0000954
67 atypical scarring of skin HP:0000987
68 aplasia cutis congenita HP:0001057
69 preaxial hand polydactyly HP:0001177
70 seizures HP:0001250
71 intellectual disability, mild HP:0001256
72 intrauterine growth retardation HP:0001511
73 nasal speech HP:0001611
74 hypoplastic fingernail HP:0001804
75 gastroesophageal reflux HP:0002020
76 pyloric stenosis HP:0002021
77 low posterior hairline HP:0002162
78 white forelock HP:0002211
79 premature graying of hair HP:0002216
80 agenesis of cerebellar vermis HP:0002335
81 supernumerary nipple HP:0002558
82 kyphosis HP:0002808
83 elbow flexion contracture HP:0002987
84 hyperlordosis HP:0003307
85 clinodactyly of the 5th finger HP:0004209
86 dermal atrophy HP:0004334
87 postauricular pit HP:0004464
88 preauricular pit HP:0004467
89 malrotation of colon HP:0004785
90 duplication of internal organs HP:0005217
91 depressed nasal bridge HP:0005280
92 fusion of middle ear ossicles HP:0005473
93 wide intermamillary distance HP:0006610
94 microtia HP:0008551
95 hypoplastic superior helix HP:0008559
96 supraauricular pit HP:0008606
97 proximal placement of thumb HP:0009623
98 short thumb HP:0009778
99 branchial anomaly HP:0009794
100 ectopic thymus tissue HP:0010517
101 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 Syndrome25 23 TFAP2A

Anatomical Context for Branchiooculofacial Syndrome

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MalaCards organs/tissues related to Branchiooculofacial Syndrome:

34
Skin, Eye, Thymus, Colon, Kidney

Animal Models for Branchiooculofacial Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Branchiooculofacial Syndrome:

39 (show all 20)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053677.8BMP4, EYA1, MAFB, PAX3, SALL1, TP63
2MP:00053777.5ATP8B1, BMP4, EYA1, IRF6, MAFB, MSX1
3MP:00107717.4BMP4, DSP, GRHL3, IRF6, MSX1, PAX3
4MP:00053917.4BMP4, EYA1, GRHL3, MSX1, PAX3, SIX5
5MP:00053697.2BMP4, DSP, EYA1, MSX1, PAX3, PKP2
6MP:00053887.1BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
7MP:00053796.9BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
8MP:00028736.9BMP4, EYA1, GDF3, GRHL3, MAFB, PAX3
9MP:00053716.8BMP4, GRHL3, IRF6, MSX1, PAX3, SALL1
10MP:00053826.6BMP4, DSP, EYA1, GRHL3, IRF6, MAFB
11MP:00053866.5BMP4, DACH1, EYA1, GRHL3, MAFB, MSX1
12MP:00053816.4BMP4, DSP, EYA1, GRHL3, IRF6, MSX1
13MP:00036316.4ATP8B1, BMP4, DACH1, DSP, EYA1, GRHL3
14MP:00053856.2BMP4, DSP, EYA1, GRHL3, MAFB, MSX1
15MP:00053806.2BMP4, DSP, EYA1, GDF3, GRHL3, IRF6
16MP:00053846.0BMP4, DACH1, DSP, EYA1, GDF3, GRHL3
17MP:00053905.9BMP4, DACH1, EYA1, GRHL3, IRF6, MAFB
18MP:00053765.6ATP8B1, BMP4, DACH1, EYA1, GDF3, GRHL3
19MP:00053785.4ATP8B1, BMP4, DSP, EYA1, GDF3, GRHL3
20MP:00107684.6ATP8B1, BMP4, DACH1, DSP, EYA1, GDF3

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:

68
id Symbol AA change Variation ID SNP ID
1TFAP2Ap.Leu249ProVAR_045838
2TFAP2Ap.Arg254GlyVAR_045839
3TFAP2Ap.Arg255GlyVAR_045840rs121909574
4TFAP2Ap.Gly262GluVAR_045841rs121909575

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 pathwaysScoreTop Affiliating Genes
18.7BMP4, IRF6, MSX1, TP63
28.5BMP4, 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:003005710.0DSP, PKP2
2nucleoplasmGO:00056546.8EYA1, GRHL3, MSX1, PAX3, PKP2, SALL1
3cytoplasmGO:00057376.2BMP4, DACH1, DSP, EYA1, GDF3, GRHL3
4nucleusGO:00056345.9DACH1, DSP, EYA1, GRHL3, IRF6, KCTD1

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

(show all 40)
idNameGO IDScoreTop Affiliating Genes
1eyelid development in camera-type eyeGO:006102910.8GRHL3, TFAP2A
2outer ear morphogenesisGO:004247310.7EYA1, SALL1
3cochlea morphogenesisGO:009010310.6EYA1, GRHL3
4middle ear morphogenesisGO:004247410.6EYA1, MSX1
5negative regulation of transcription by competitive promoter bindingGO:001094410.4DACH1, TFAP2A
6regulation of cell fate commitmentGO:001045310.4BMP4, GDF3
7mesenchymal to epithelial transition involved in metanephros morphogenesisGO:000333710.3BMP4, SALL1
8keratinocyte proliferationGO:004361610.2IRF6, TP63
9epithelial to mesenchymal transition involved in endocardial cushion formationGO:000319810.2BMP4, MSX1
10BMP signaling pathway involved in heart developmentGO:006131210.2BMP4, MSX1
11negative regulation of myoblast differentiationGO:004566210.2BMP4, GDF3
12establishment of planar polarityGO:000173610.1GRHL3, TP63
13establishment of skin barrierGO:006143610.1GRHL3, TP63
14inner ear morphogenesisGO:004247210.1EYA1, MAFB, TFAP2A
15cloacal septationGO:006019710.0BMP4, TP63
16kidney developmentGO:000182210.0BMP4, SALL1, TFAP2A
17ureteric bud developmentGO:00016579.9BMP4, EYA1, SALL1
18branching involved in ureteric bud morphogenesisGO:00016589.9BMP4, EYA1, SALL1
19pattern specification processGO:00073899.9EYA1, GRHL3, TP63
20pituitary gland developmentGO:00219839.8BMP4, MSX1, SALL1
21bundle of His cell-Purkinje myocyte adhesion involved in cell communicationGO:00860739.8DSP, PKP2
22embryonic digit morphogenesisGO:00427339.8BMP4, MSX1, SALL1
23smooth muscle tissue developmentGO:00487459.8BMP4, TP63
24regulation of ventricular cardiac muscle cell action potentialGO:00989119.8DSP, PKP2
25anatomical structure formation involved in morphogenesisGO:00486469.7BMP4, TP63
26keratinocyte differentiationGO:00302169.7DSP, IRF6, TP63
27epidermis developmentGO:00085449.7DSP, GRHL3, TP63
28skeletal system developmentGO:00015019.4BMP4, GDF3, TP63
29odontogenesis of dentin-containing toothGO:00424759.4BMP4, MSX1, TP63
30animal organ morphogenesisGO:00098879.3EYA1, PAX3, TP63
31embryonic limb morphogenesisGO:00303269.3BMP4, MSX1, TP63
32sensory perception of soundGO:00076059.2ATP8B1, EYA1, PAX3, TFAP2A
33wound healingGO:00420609.2BMP4, DSP, GRHL3
34heart developmentGO:00075079.0BMP4, MSX1, PKP2, SALL1
35negative regulation of cell proliferationGO:00082858.6BMP4, IRF6, MSX1, PKP2, SIX5, TFAP2A
36transcription from RNA polymerase II promoterGO:00063668.2GRHL3, MAFB, MSX1, PAX3, TFAP2A, TP63
37positive regulation of transcription, DNA-templatedGO:00458937.7BMP4, EYA1, GRHL3, IRF6, PAX3, SALL1
38negative regulation of transcription from RNA polymerase II promoterGO:00001227.7BMP4, DACH1, MSX1, SALL1, TBX22, TFAP2A
39negative regulation of transcription, DNA-templatedGO:00458927.1ATP8B1, BMP4, DACH1, KCTD1, MSX1, SALL1
40positive regulation of transcription from RNA polymerase II promoterGO:00459446.3BMP4, EYA1, GRHL3, 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
2transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific bindingGO:000107810.1DACH1, SALL1, TFAP2A
3cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communicationGO:008608310.0DSP, PKP2
4transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific bindingGO:000122810.0GRHL3, MAFB, MSX1
5RNA polymerase II core promoter proximal region sequence-specific DNA bindingGO:00009789.9MAFB, SALL1, SIX5, TFAP2A
6transcription factor activity, sequence-specific DNA bindingGO:00037008.3DACH1, IRF6, PAX3, SALL1, TBX22, TP63
7sequence-specific DNA bindingGO:00435657.7GRHL3, MSX1, PAX3, SALL1, SIX5, TFAP2A
8DNA bindingGO:00036777.2DACH1, GRHL3, IRF6, MAFB, MSX1, SALL1
9protein bindingGO:00055153.8ATP8B1, BMP4, DACH1, DSP, EYA1, GDF3

Sources for Branchiooculofacial Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
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44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet