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


Orphanet epidemiological data:

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


branchiooculofacial syndrome:
Inheritance: autosomal dominant inheritance


External Ids:

OMIM49 113620
Disease Ontology10 DOID:0050691
Orphanet51 1297
ICD10 via Orphanet28 Q18.8
UMLS via Orphanet66 C0376524
MedGen34 C0376524
MeSH36 D019280
UMLS65 C0376524

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 c9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia, and has symptoms including sacrococcygeal pilonidal abnormality, external ear malformation and aplasia/hypoplasia of the skin. 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 kidney, and related mouse phenotypes are renal/urinary system and vision/eye.

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

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.

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.

GeneReviews summary for NBK55063

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 34)
idRelated DiseaseScoreTop Affiliating Genes
1burn-mckeown syndrome11.3
2c9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia10.7EYA1, SIX5
3popliteal pterygium syndrome 110.5GRHL3, IRF6, TFAP2A
4tooth agenesis, selective, 210.4EYA1, SALL1
5renal tubular dysgenesis, ace-related10.4EYA1, SALL1
6pancreatic and cerebellar agenesis10.4EYA1, SALL1, SIX5
7schimke immunoosseous dysplasia10.3IRF6, TBX22
8familial isolated arrhythmogenic ventricular dysplasia, left dominant form10.2DSP, PKP2
11pulmonic stenosis10.2
13colobomatous microphthalmia10.2
14frontotemporal dementia, right temporal atrophy variant10.2DSP, PKP2
15tooth ankylosis10.2SALL1, TP63
16mitf-related melanoma and renal cell carcinoma predisposition syndrome10.2DSP, PKP2
17mixed receptive-expressive language disorder10.2SALL1, TP63
18arrhythmogenic right ventricular dysplasia 1210.2DSP, PKP2
19nonsyndromic congenital nail disorder 210.2TBX22, TP63
20carnitine palmitoyltransferase ii deficiency10.1EYA1, SIX5
21type i ehlers-danlos syndrome10.1DACH1, EYA1, SALL1, SIX5
22variola minor10.1MSX1, TBX22
23cystic teratoma10.1MAFB, TP63
24focal dermal hypoplasia10.0
25ectodermal dysplasia10.0
26ectopic thymus9.9
27visual pathway disease9.9EYA1, SIX5, TFAP2A, TP63
28limb-mammary syndrome9.9PKP2, TP63
29dysbaric osteonecrosis9.6IRF6, MSX1, TBX22, TP63
30lip disease9.2BMP4, IRF6, MSX1, TFAP2A, TP63
31spondylocostal dysostosis9.2BMP4, IRF6, MSX1, TBX22, TP63
32myasthenic syndrome, congenital, 2a, slow-channel9.2BMP4, IRF6, MSX1, TBX22, TP63
33asphyxiating thoracic dystrophy8.9BMP4, DSP, IRF6, MSX1, TP63
34auriculocondylar syndrome 34.8ATP8B1, 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:


Clinical features from OMIM:



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

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 TFAP2A

Anatomical Context for Branchiooculofacial Syndrome

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MalaCards organs/tissues related to Branchiooculofacial Syndrome:

Skin, Eye, Kidney, Prostate, Thymus, Colon, T cells

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:00053917.6BMP4, EYA1, GRHL3, MSX1, PAX3, SIX5
3MP:00053717.5BMP4, GRHL3, IRF6, MSX1, PAX3, SALL1
4MP:00107717.3BMP4, DSP, GRHL3, IRF6, MSX1, PAX3
5MP:00053797.2BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
6MP:00028737.1BMP4, EYA1, GDF3, GRHL3, MAFB, PAX3
7MP:00053887.1BMP4, DACH1, EYA1, MAFB, MSX1, PAX3
8MP:00053697.0BMP4, DSP, EYA1, MSX1, PAX3, PKP2
9MP:00053866.8BMP4, DACH1, EYA1, GRHL3, MAFB, MSX1
10MP:00053776.7ATP8B1, BMP4, EYA1, IRF6, MAFB, MSX1
11MP:00053816.4BMP4, DSP, EYA1, GRHL3, IRF6, MSX1
12MP:00036316.4ATP8B1, BMP4, DACH1, DSP, EYA1, GRHL3
13MP:00053806.3BMP4, DSP, EYA1, GDF3, GRHL3, IRF6
14MP:00053826.2BMP4, DSP, EYA1, GRHL3, IRF6, MAFB
15MP:00053905.9BMP4, DACH1, EYA1, GRHL3, IRF6, MAFB
16MP:00053765.9ATP8B1, BMP4, DACH1, EYA1, GDF3, GRHL3
17MP:00053855.9BMP4, DSP, EYA1, GRHL3, MAFB, MSX1
18MP:00053845.8BMP4, DACH1, DSP, EYA1, GDF3, GRHL3
19MP:00053785.4ATP8B1, BMP4, DSP, EYA1, GDF3, GRHL3
20MP:00107684.4ATP8B1, BMP4, DACH1, DSP, EYA1, GDF3

Publications for Branchiooculofacial Syndrome

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Articles related to Branchiooculofacial Syndrome:

Branchiootorenal and branchiooculofacial syndrome. (25569411)
Branchiooculofacial syndrome and bilateral ectopic thymus: report of a family. (23106675)
Branchiooculofacial Syndrome (21634087)

Variations for Branchiooculofacial Syndrome

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

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Branchiooculofacial Syndrome:

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

(show all 30)
idNameGO IDScoreTop Affiliating Genes
1cochlea morphogenesisGO:009010310.6EYA1, GRHL3
2negative regulation of transcription by competitive promoter bindingGO:001094410.5DACH1, TFAP2A
3outer ear morphogenesisGO:004247310.5EYA1, SALL1
4inner ear morphogenesisGO:004247210.3EYA1, MAFB
5regulation of cell fate commitmentGO:001045310.3BMP4, GDF3
6mesenchymal to epithelial transition involved in metanephros morphogenesisGO:000333710.3BMP4, SALL1
7establishment of planar polarityGO:000173610.3GRHL3, TP63
8embryonic cranial skeleton morphogenesisGO:004870110.2BMP4, TFAP2A
9negative regulation of myoblast differentiationGO:004566210.2BMP4, GDF3
10positive regulation of Notch signaling pathwayGO:004574710.2EYA1, TP63
11embryonic forelimb morphogenesisGO:003511510.2MSX1, TFAP2A
12pituitary gland developmentGO:002198310.2BMP4, SALL1
13bone morphogenesisGO:006034910.2MSX1, TFAP2A
14SMAD protein signal transductionGO:006039510.1BMP4, GDF3
15embryonic hindlimb morphogenesisGO:003511610.1BMP4, MSX1
16odontogenesisGO:004247610.1BMP4, MSX1
17cloacal septationGO:006019710.0BMP4, TP63
18kidney developmentGO:00018229.9BMP4, SALL1, TFAP2A
19ureteric bud developmentGO:00016579.8BMP4, EYA1, SALL1
20embryonic digit morphogenesisGO:00427339.8BMP4, MSX1, SALL1
21establishment of skin barrierGO:00614369.7GRHL3, TP63
22BMP signaling pathwayGO:00305099.7BMP4, GDF3, MSX1
23negative regulation of cell proliferationGO:00082859.7BMP4, PKP2, TFAP2A
24anatomical structure formation involved in morphogenesisGO:00486469.0BMP4, TP63
25embryonic limb morphogenesisGO:00303268.9BMP4, MSX1, TP63
26negative regulation of apoptotic processGO:00430668.9BMP4, MSX1, TFAP2A, TP63
27positive regulation of transcription from RNA polymerase II promoterGO:00459448.2BMP4, EYA1, MAFB, SALL1, TFAP2A, TP63
28positive regulation of transcription, DNA-templatedGO:00458938.0BMP4, EYA1, GRHL3, PAX3, SALL1, TFAP2A
29regulation of transcription, DNA-templatedGO:00063557.8DACH1, EYA1, IRF6, MAFB, PAX3, TFAP2A
30negative regulation of transcription, DNA-templatedGO:00458927.5ATP8B1, BMP4, DACH1, MSX1, SALL1, SIX5

Sources for Branchiooculofacial Syndrome

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28ICD10 via Orphanet
37MESH via Orphanet
50OMIM via Orphanet
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
66UMLS via Orphanet