National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Branchiooculofacial syndrome


Other Names:
BOFS syndrome; Branchial clefts with characteristic facies growth retardation imperforate nasolacrimal duct and premature aging; Hemangiomatous branchial clefts-lip pseudocleft syndrome; BOFS syndrome; Branchial clefts with characteristic facies growth retardation imperforate nasolacrimal duct and premature aging; Hemangiomatous branchial clefts-lip pseudocleft syndrome; Lip pseudocleft-hemangiomatous branchial cyst syndrome See More
Categories:
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.[1][2][3]
Last updated: 6/23/2011
The characteristic signs and symptoms of BOFS include skin defects, eye abnormalities, and distinctive facial features. These features vary among affected individuals. The skin defects include proliferation of blood vessels (hemangiomatous) in the lower neck or upper chest; lumps in the area of the neck or collarbone (branchial cleft sinuses); and linear skin lesions behind the ears. Eye abnormalities can include microphthalmia, coloboma, and strabismus. The distinctive facial features can include widely spaced eyes; the presence of a pseudocleft of the upper lip resembling a poorly repaired cleft lip; a malformed nose with a broad bridge and flattened tip; blockage of the tear ducts (lacrimal duct obstruction); and malformed ears. Often, affected individuals may have burn-like lesions behind the ears. Other features can include delayed growth, thymic and kidney abnormalities, dental abnormalities, and hearing loss. Intellect is usually normal.[1][2][3] 
Last updated: 6/23/2011

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 95 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears
[ more ] 		0000377
Atypical scarring of skin
Atypical scarring
0000987
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Deep philtrum 0002002
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip
[ more ] 		0000232
Hemangioma
Strawberry mark
0001028
Low-set, posteriorly rotated ears 0000368
Postauricular pit
Pit behind the ear
0004464
Preauricular pit
Pit in front of the ear
0004467
Supraauricular pit
Pit above the ear
0008606
30%-79% of people have these symptoms
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose
[ more ] 		0000455
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Fingernail dysplasia
Abnormal fingernail development
0100798
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Intrauterine growth retardation
Prenatal growth retardation
Prenatal growth deficiency
[ more ] 		0001511
Iris coloboma
Cat eye
0000612
Microdontia
Decreased width of tooth
0000691
Nasal speech
Nasal voice
0001611
Nasolacrimal duct obstruction
Blocked tear duct
0000579
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ] 		0002167
Non-midline cleft lip 0100335
Premature graying of hair
Premature hair graying
Early graying
Premature graying
Premature greying
[ more ] 		0002216
Reduced number of teeth
Decreased tooth count
0009804
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
5%-29% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Hydronephrosis 0000126
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Multicystic kidney dysplasia 0000003
Preaxial hand polydactyly
Extra thumb
0001177
Ptosis
Drooping upper eyelid
0000508
Renal agenesis
Absent kidney
Missing kidney
[ more ] 		0000104
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Upper lip pit 0100268
1%-4% of people have these symptoms
Cleft of chin 0011323
Dimple chin
Chin butt
Chin dent
Chin dimple
Chin skin dimple
Indentation of chin
[ more ] 		0010751
Facial palsy
Bell's palsy
0010628
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Microphthalmia
Abnormally small eyeball
0000568
Postnatal growth retardation
Growth delay as children
0008897
Retinal coloboma
Hole in the back of the eye
0000480
Sparse hair 0008070
Percent of people who have these symptoms is not available through HPO
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality
[ more ] 		0000164
Agenesis of cerebellar vermis 0002335
Anophthalmia
Absence of eyeballs
Failure of development of eyeball
Missing eyeball
No eyeball
[ more ] 		0000528
Aplasia cutis congenita
Absence of part of skin at birth
0001057
Autosomal dominant inheritance 0000006
Branchial anomaly 0009794
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Dermal atrophy
Skin degeneration
0004334
Dermoid cyst 0025247
Duplication of internal organs 0005217
Ectopic thymus tissue
Abnormal thymus position
0010517
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures
[ more ] 		0002987
Fusion of middle ear ossicles 0005473
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Hamartoma 0010566
Hyperlordosis
Prominent swayback
0003307
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplastic fingernail
Small fingernail
Underdeveloped fingernail
[ more ] 		0001804
Hypoplastic superior helix 0008559
Hypospadias 0000047
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ] 		0001256
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Low posterior hairline
Low hairline at back of neck
0002162
Lower lip pit 0000196
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Malar flattening
Zygomatic flattening
0000272
Malrotation of colon 0004785
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Microtia
Small ears
Underdeveloped ears
[ more ] 		0008551
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Overfolded helix
Overfolded ears
0000396
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Proximal placement of thumb
Attachment of thumb close to wrist
0009623
Pyloric stenosis 0002021
Renal cyst
Kidney cyst
0000107
Seizure 0001250
Sensorineural hearing impairment 0000407
Short nasal septum
Decreased length of nasal septum
Decreased length of septum of nose
Short septum of nose
[ more ] 		0000420
Short neck
Decreased length of neck
0000470
Short thumb
Short thumbs
Small thumbs
[ more ] 		0009778
Single transverse palmar crease 0000954
Small forehead
Decreased size of forehead
0000350
Supernumerary nipple
Accessory nipple
0002558
Telecanthus
Corners of eye widely separated
0000506
White forelock
White part of hair above forehead
0002211
Wide intermamillary distance
Wide-spaced nipples
Widely spaced nipples
Widely-spaced nipples
[ more ] 		0006610
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Last updated: 7/1/2020
Although some cases can be sporadic, most of the reported cases are inherited within families. BOFS is inherited in an autosomal dominant pattern, which means that one copy of the altered TFAP2A gene in each cell is sufficient to cause this condition.[2][3]
Last updated: 6/23/2011
BOFS can be diagnosed clinically based on the characteristic features of this condition. Genetic testing can also confirm the diagnosis.[3] GeneTests lists the names of laboratories that are performing genetic testing for branchiooculofacial syndrome. To view the contact information for the clinical laboratories conducting testing, click here. To access the contact information for the research laboratories performing genetic testing, click here.

Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
Last updated: 6/23/2011

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
BOFS should be differentiated from the branchio-oto-renal syndrome (BOR syndrome; see this term).
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Branchiooculofacial syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Branchiooculofacial syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I would like information on branchiooculofacial syndrome. My son was born with a bilateral cleft lip and palate, low-set ears with dimpled ear lobes, and some type of odd lesions in the branchial sinus area on one side and a pit on the other. His sister has an odd raised line on her neck in the same place and also has the dimpled ear-lobes, which led me to believe its a genetic issue. See answer


  1. Branchio Oculo Facial Syndrome. National Organization for Rare Disorders (NORD). 2007; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/714/viewAbstract. Accessed 6/23/2011.
  2. Branchio-oculo-facial syndrome. Orphanet. January 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1297. Accessed 6/23/2011.
  3. Lin AAE & Milunsky JM. Branchiooculofacial Syndrome. GeneReviews. May 31, 2011; http://www.ncbi.nlm.nih.gov/books/NBK55063/. Accessed 6/23/2011.