Paula and Bobby
Parents of Lillie
Branchiooculofacial syndrome (BOFS)
What is Branchiooculofacial syndrome (BOFS)?
This rare disease is a genetic condition first identified in 1987.
The main features and symptoms of the syndrome affect the eyes, the skin, and other facial features.
The syndrome also affects the kidneys of affected individuals.
This syndrome is also known as:
Bof Syndrome; BOFS; Branchial Clefts With Characteristic Facies, Growth Retardation, Imperforate Nasolacrimal Duct, And Premature Aging Haemangiomatous branchial clefts - pseudocleft syndrome Haemangiomatous branchial clefts - pseudoclefts syndrome Hemangiomatous Branchial Clefts-lip Pseudocleft Syndrome Lip Pseudocleft-hemangiomatous Branchial Cyst Syndrome
What gene changes cause Branchiooculofacial syndrome (BOFS)?
Mutations to the TFAP2A are responsible for causing the syndrome. It is inherited in an autosomal dominant pattern but over half of all cases are the result of a de novo or random mutation.
In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.
What are the main symptoms of Branchiooculofacial syndrome (BOFS)?
The main symptoms affecting the eyes are small or absent eyeballs which can cause issues with vision.
Coloboma, a hole in the eye, and early cataracts (a clouding of the eye) are other issues related to the syndrome. Blocked tear ducts are another common symptom.
Skin scarring, connected to issues with the development of the branchial arches while the fetus is in utero, is also a common feature of the syndrome. This scarring occurs mainly on the neck and can present as thick patches, overly hairy patches. They may also be very red and filled with blood vessels.
Other unique facial characteristics of the condition include widely-spaced eyes, a cleft or pseudo cleft lip, a high forehead, a broad nose and flat tip of the nose, and abnormalities with the development of the nails and teeth. Some individuals may also experience premature greying of the hair.
Individuals may also experience kidney abnormalities and problems, including the development of cysts.
Possible clinical traits/features:
Lip pit, Nasolacrimal duct obstruction, Neurological speech impairment, Myopia, Lower lip pit, Malrotation of colon, Low-set ears, Low posterior hairline, Low-set, posteriorly rotated ears, Intellectual disability, mild, Intrauterine growth retardation, Iris coloboma, Preauricular pit, Multicystic kidney dysplasia, Microdontia, Micrognathia, Microphthalmia, Microtia, Atypical scarring of skin, Abnormality of the dentition, Abnormality of the voice, Abnormal palate morphology, Abnormality of the nose, Agenesis of cerebellar vermis, Aplasia/Hypoplasia of the skin, Aplasia cutis congenita, Abnormal fingernail morphology, Lacrimation abnormality, Broad nasal tip, Branchial anomaly, Cataract, Short stature, Hypoplastic fingernail, Hypoplastic superior helix, Nasal speech, Hyperlordosis, Kyphosis, Hypertelorism, Short thumb, Hypospadias, Gastroesophageal reflux, Depressed nasal bridge, Fusion of middle ear ossicles, Hamartoma, Postnatal growth retardation, Autosomal dominant inheritance, Overfolded helix, Postauric
How does someone get tested for Branchiooculofacial syndrome (BOFS)?
The initial testing for Branchiooculofacial syndrome (BOFS) can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Branchiooculofacial syndrome (BOFS)
The main features of this disorder include hypertrophy of the lateral pillars of the philtrum (it may look like a poorly repaired cleft); a broad, asymmetric nose with a broad tip; lacrimal duct obstruction; and a branchial sinus or linear skin lesion behind the ear. Coloboma of the iris and/or retina are common, and auricular and lip pits are also frequent. Some of those affected, but not all, are short and have intellectual disability.
The two excellent handles in this condition are the pseudoclefts - which are prominent, bilateral, vertical ridges between the lip and the nose - and the hemangiomatous lesions behind the ear at the angle of the jaw, which can be associated with ectopic thymic tissue. Lesser forms (microforms and mini-microforms) of labial clefting also occur and might be overlooked (Lin et al., 2009).
Ear malformations are common, and one case is pictured as having deep pits on the posterior surface of the ear itself. Bilateral cochlear dysplasia, enlarged vestibule and enlarged vestibular aqueduct have been reported (Tekin et al., 2009). Abnormalities in the middle and inner ear were reported by Lugli et al., (2015).
Preaxial polydactyly of the thumb may be an occasional feature (Fujimoto et al., 1987, McGaughran 2001).
Lin et al., (1995) reviewed 43 patients from the literature, including 15 new cases. Lin et al., (1991) reviewed 13 reported cases and added the evaluations of two new patients.
Richardson et al., (1996) reported a three-generation pedigree. A three-generation family with variable expression (one died at 6 hours - he was premature and had agenesis of one kidney) was reported by Titheradge et al., (2015).
In three families a parent has been affected, and premature graying of the hair occurred in them (Fujimoto et al., 1987).
Lee et al., (1982) reported a mother and son with bilateral branchial sinuses, low birth weight, short stature and an unusual facial appearance. There was a mild upward eye slant, a prominent nose, a short philtrum, a prominent upper lip, downturned corners of the mouth and prominent ears. The mother's hair went gray at 18 years, and she had an aged facial appearance. At 38 years, she had periodontosis and early cataract formation.
Megarbane et al., (1998) reported a father and daughter with features of the condition. The father had a convincing white forelock. Fielding and Fryer (1992) reported a brother and sister with normal parents. They both had hemangiomatous orbital cysts in addition to the classical features of the condition.
McCool and Weaver (1994) reported a mother and son who were relatively mildly affected and had the unusual manifestation of a supra-auricular sinus. The child had unilateral renal agenesis, which is a rare feature of the condition. Kulkarni et al., (2005) also reported three members of a family with mild involvement (pseudocleft in one, prominent philtral pillars in two others, and a broad nasal tip and telecanthus in all three).
Two unrelated cases were reported by Hall et al., (1983). Both had operations for obstructed nasolacrimal ducts, and one had unilateral microphthalmia. Intelligence was normal. A minor anomaly was retroversion of the ears with uplifted lobules.
Mazzone et al., (1992) reported a case with agenesis of the cerebellar vermis. Schmerler et al., (1992) reported a 12-year-old boy with normal intelligence.
The single case reported by Demirci et al., (2005) is difficult to place. There was no pseudocleft nor hemangiomatous skin lesion, and the eye anomalies were unusual (left orbital dermoid, an iris pigment epithelial cyst on the other side, and combined hamartoma of the retina and retinal pigment epithelium). There was a branchial cleft and openings of fistulae on each side of the nose, connecting the lacrimal sac to the skin.
The condition has been mapped to 6p24 and mutations found in TFAP2A (Milunsky et al., 2008, Stoetzel et al., 2009). Lin et al., (2000) excluded linkage to the BOR region on chromosome 8. Correa-Cerro et al., (2000) excluded linkage to EYA1-4 genes. Trummer et al., (2002) also produced data suggesting that BOF and BOR are separate entities.
* This information is courtesy of the L M D.
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