Branchio-oculo-facial syndrome (BOFS)
is a disease that arises from a mutation in the
TFAP2A
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in humans is encoded by the ''TFAP2A'' gene.
Function
Transcription factor AP-2 alpha is a 52-kD sequence-specific DNA-bindi ...
gene. It is a rare
autosomal dominant disorder that starts to affect a child's development before birth.
Symptoms of this condition include skin abnormalities on the neck, deformities of the ears and eyes, and other distinctive facial features such a
cleft lip
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
along with slow growth,
mental retardation
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...
and premature graying of hair.
Signs and symptoms
"Branchio" refers to the
branchial arch
Branchial arches, or gill arches, are a series of bony "loops" present in fish, which support the gills. As gills are the primitive condition of vertebrates, all vertebrate embryos develop pharyngeal arches, though the eventual fate of these arc ...
es, also known as the pharyngeal arches, of the affected individual. The branchial arches are structures in the developing
embryo that give rise to certain tissues in the neck and facial area. In individuals affected by this condition, the branchial arches fail to develop properly. This leads to some of the physical conditions of this syndrome, which include abnormal patches of skin on the neck and face region and can be abnormally hairy, thin or red and with a high number of blood vessels. "Oculo" refers to the eyes. Individuals have
vision impairment
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
due to several malformations in the eyes such as small eyeballs, blockage in the tear ducts or lacking eyes completely. "Facial" refers to the face; those affected can have several abnormalities in that region. These abnormalities include a cleft lip, a
cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...
which is an opening in the roof of the mouth, widely spaced eyes (
hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...
), sharp corners of the mouth that point upward, a broad nose that can include a flattened tip, along with several deformations of both the external and
middle ear
The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear).
The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in the ...
structures. This syndrome is restricted to the face, but it can also cause underdeveloped or malformed kidneys.
Pathophysiology
The disease is genetically inherited and stems from a mutation that deletes the
TFAP2A
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in humans is encoded by the ''TFAP2A'' gene.
Function
Transcription factor AP-2 alpha is a 52-kD sequence-specific DNA-bindi ...
gene. This gene is important because it provides the blueprint for the arrangement of 437
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s that make up the protein
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
known as AP-2 alpha. This protein transcription factor binds to a carboxy terminus helix-span-helix motif and an amino terminus portion of DNA that affects the activity of numerous cellular activities such as
cell division
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
and
apoptosis. AP-2 alpha is especially important during the embryos development principally in the development of the branchial arches. Currently there are also four other proteins that are affected by the deletion of TFAP2A gene as well. One is
L249P, this protein changes to cause a conformational space change with a substituted
proline. Furthermore, a change in the
R254W and
R255G
R, or r, is the eighteenth Letter (alphabet), letter of the Latin alphabet, used in the English alphabet, modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is English alphabe ...
proteins results in a replacement of a charged polar side chain by a nonpolar side chain, and lastly, an alteration in the
G262E protein results in a nonpolar side chain being replaced by a charged polar side chain.
Diagnosis
Branchio-oculo-facial syndrome is difficult to diagnose because it has
incomplete penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype). In medical genetics, the penetrance of a disease-causing mutation is t ...
. It is often misdiagnosed as
branchio-oto-renal syndrome because of their similarities in symptoms.
Management
The care and management of people with BOFS is aimed at the specific signs and symptoms, and should be carried out by a multi-specialty team who are skilled in craniofacial disorders. A medical geneticist usually makes the clinical diagnosis, which is confirmed with molecular testing. Reconstructive surgery is needed to repair facial deformities and obstructed nasal ducts. Importantly, the skin defects should not be treated with simple cauterization. Strabismus ("crossed eyes") may be corrected by surgery.
In addition, people with BOFS should be managed by an ophthalmologist, otolaryngologist, dentist, and speech therapist. Depending on the person's issues, there may be a need for a neuropsychologic or developmental evaluation and mental health support.
Genetic counseling is recommended for the patients and their families for reproductive health.
Epidemiology
It was estimated that only 100 cases of BOFS have been documented in the medical literature .
References
External links
{{Medical resources
, DiseasesDB =
, ICD10 = Q18.8
, ICD9 =
, ICDO =
, OMIM = 113620
, MedlinePlus =
, eMedicineSubj =
, eMedicineTopic =
, MeSH =
, GeneReviewsNBK =
, GeneReviewsName =
, Orphanet = 1297
, SNOMED CT = 449821007
Genetic diseases and disorders
Transcription factor deficiencies
Rare syndromes
Syndromes with intellectual disability
Syndromes with cleft lip and/or palate