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Branchio-oculo-facial syndrome

Reviewed September 2012

What is branchio-oculo-facial syndrome?

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.

"Branchio-" refers to the branchial arches, which are structures in the developing embryo that give rise to tissues in the face and neck. In people with branchio-oculo-facial syndrome, the first and second branchial arches do not develop properly, leading to abnormal patches of skin, typically on the neck or near the ears. These patches can be unusually thin, hairy, or red and densely packed with blood vessels (hemangiomatous). In a small number of individuals, tissue from a gland called the thymus is abnormally located on the skin of the neck (dermal thymus). Problems with branchial arch development underlie many of the other features of branchio-oculo-facial syndrome.

"Oculo-" refers to the eyes. Many people with branchio-oculo-facial syndrome have malformations of the eyes that can lead to vision impairment. These abnormalities include unusually small eyeballs (microphthalmia), no eyeballs (anophthalmia), a gap or split in structures that make up the eyes (coloboma), or blockage of the tear ducts (nasolacrimal duct stenosis).

Problems with development of the face lead to distinctive facial features in people with branchio-oculo-facial syndrome. Many affected individuals have a split in the upper lip (cleft lip) or a pointed upper lip that resembles a poorly repaired cleft lip (often called a pseudocleft lip) with or without an opening in the roof of the mouth (cleft palate). Other facial characteristics include widely spaced eyes (hypertelorism), an increased distance between the inner corners of the eyes (telecanthus), outside corners of the eyes that point upward (upslanting palpebral fissures), a broad nose with a flattened tip, and weakness of the muscles in the lower face. The ears are also commonly affected, resulting in malformed or prominent ears. Abnormalities of the inner ear or of the tiny bones in the ears (ossicles) can cause hearing loss in people with this condition.

Branchio-oculo-facial syndrome can affect other structures and tissues as well. Some affected individuals have kidney abnormalities, such as malformed kidneys or multiple kidney cysts. Nail and teeth abnormalities also occur, and some people with this condition have prematurely graying hair.

How common is branchio-oculo-facial syndrome?

Branchio-oculo-facial syndrome is a rare condition, although the prevalence is unknown.

What genes are related to branchio-oculo-facial syndrome?

Branchio-oculo-facial syndrome is caused by mutations in the TFAP2A gene. This gene provides instructions for making a protein called transcription factor AP-2 alpha (AP-2α). As its name suggests, this protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2α regulates genes that are involved in several cellular processes, such as cell division and the self-destruction of cells that are no longer needed (apoptosis). This protein is critical during development before birth, particularly of the branchial arches, which form the structures of the face and neck.

Most TFAP2A gene mutations that cause branchio-oculo-facial syndrome change single protein building blocks (amino acids) in the transcription factor AP-2α protein. These changes tend to occur in a region of the protein that allows it to bind to DNA. Without this function, transcription factor AP-2α cannot control the activity of genes during development, which disrupts the development of the eyes, ears, and face and causes the features of branchio-oculo-facial syndrome.

Related Gene(s)

Changes in this gene are associated with branchio-oculo-facial syndrome.

  • TFAP2A

How do people inherit branchio-oculo-facial syndrome?

Branchio-oculo-facial syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In about half of cases, an affected person inherits the mutation from one affected parent. The remaining cases occur in people whose parents do not have a mutation in the TFAP2A gene. In these situations, the mutation likely occurs as a random event during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development of the affected individual.

Where can I find information about diagnosis or management of branchio-oculo-facial syndrome?

These resources address the diagnosis or management of branchio-oculo-facial syndrome and may include treatment providers.

  • Gene Review: Branchiooculofacial Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK55063)
  • Genetic Testing Registry: Branchiooculofacial syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0376524)
  • MedlinePlus Encyclopedia: Cleft Lip and Palate (http://www.nlm.nih.gov/medlineplus/ency/article/001051.htm)

You might also find information on the diagnosis or management of branchio-oculo-facial syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/branchio-oculo-facial-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about branchio-oculo-facial syndrome?

You may find the following resources about branchio-oculo-facial syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for branchio-oculo-facial syndrome?

  • BOFS
  • branchial clefts with characteristic facies, growth retardation, imperforate nasolacrimal duct, and premature aging
  • hemangiomatous branchial clefts-lip pseudocleft syndrome
  • lip pseudocleft-hemagiomatous branchial cyst syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about branchio-oculo-facial syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding branchio-oculo-facial syndrome?

acids ; anophthalmia ; apoptosis ; autosomal ; autosomal dominant ; branchial arch ; cell ; cell division ; cleft palate ; cysts ; DNA ; duct ; embryo ; gene ; hypertelorism ; inherited ; kidney ; mutation ; palate ; prevalence ; protein ; reproductive cells ; sperm ; stenosis ; syndrome ; thymus ; tissue ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Developmental Biology (sixth edition, 2000): The Neural Crest (http://www.ncbi.nlm.nih.gov/books/NBK10065/)
  • Gene Review: Branchiooculofacial Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK55063)
  • Lin AE, Gorlin RJ, Lurie IW, Brunner HG, van der Burgt I, Naumchik IV, Rumyantseva NV, Stengel-Rutkowski S, Rosenbaum K, Meinecke P, et al. Further delineation of the branchio-oculo-facial syndrome. Am J Med Genet. 1995 Mar 13;56(1):42-59. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7747785?dopt=Abstract)
  • Milunsky JM, Maher TA, Zhao G, Roberts AE, Stalker HJ, Zori RT, Burch MN, Clemens M, Mulliken JB, Smith R, Lin AE. TFAP2A mutations result in branchio-oculo-facial syndrome. Am J Hum Genet. 2008 May;82(5):1171-7. doi: 10.1016/j.ajhg.2008.03.005. Erratum in: Am J Hum Genet. 2009 Feb;84(2):301.. (http://www.ncbi.nlm.nih.gov/pubmed/18423521?dopt=Abstract)
  • Milunsky JM, Maher TM, Zhao G, Wang Z, Mulliken JB, Chitayat D, Clemens M, Stalker HJ, Bauer M, Burch M, Chénier S, Cunningham ML, Drack AV, Janssens S, Karlea A, Klatt R, Kini U, Klein O, Lachmeijer AM, Megarbane A, Mendelsohn NJ, Meschino WS, Mortier GR, Parkash S, Ray CR, Roberts A, Roberts A, Reardon W, Schnur RE, Smith R, Splitt M, Tezcan K, Whiteford ML, Wong DA, Zori R, Lin AE. Genotype-phenotype analysis of the branchio-oculo-facial syndrome. Am J Med Genet A. 2011 Jan;155A(1):22-32. doi: 10.1002/ajmg.a.33783. (http://www.ncbi.nlm.nih.gov/pubmed/21204207?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2012
Published: March 2, 2015