Branchio-oculo-facial syndrome (BOFS) is a rare autosomal dominant disorder with highly variable expression. It is characterized by craniofacial, cervical, auricular, ophthalmologic and oral anomalies. Extracraniofacial malformations are uncommon. Atrial Septal defect and Tetralogy of Fallot’s have been described in association with BOFS(1,2). Neuro-development is normal; cases of moderate to severe retardation with hypotonia, visual, hearing and speech problems have been reported. The molecular basis of the disorder has not been elucidated.

This term neonate was born to parents with one previously normal child. The father and three paternal uncles had premature graying of hair at about 21 years and two had preauricular pits. At one year of age she was noticed to have an unusual facial appearance with a sloping forehead, midfacial clefting, left upslanted palpebral fissure, hypertelorism, micropthalmia (Left >Right), nose with broad bridge, posteriorly angulated and low set ears with preauricular pits. Discharge was present in the left eye with hypertrophy of the skin over the ducts suggesting chronic dacrocystitis. There was a strip of hemangiomatous skin in the posterior auricular area. The palate was high arched.

The nipples were normally spaced. There was a grade II/VI systolic murmur heard at the pulmonic area. An umbilical hernia was present. Left postaxial polydactyly, bilateral single transverse palmar creases were present with absent interphalangeal creases on both thumbs. She had syndactyly of the left 4th and 5th toes. Dentition was normal and hair were sparse.

Ultrasound abdomen revealed normal kidneys. Echocardiography demonstrated valvular pulmonic stenosis with no evidence of chamber hypertrophy. Puretone audiometry revealed severe sensorineural hearing loss. Karyotype was normal.

BOFS is recognized to be a neurocristopathy. Aberrant development in the area of the nasal maxillary groove leads to atresia or hypoplasia of the nasolacrimal duct(3). The craniofacial appearance consists of dolicocephaly, sparse hair, high forehead, ocular asymmetry, upslanting palpebral fissures, hypertelorism and a wide nasal bridge with a flat tip and midfacial clefting. The auricles are low set, posteriorly rotated with a thin helix. Distortion of the upper lip due to hyper- trophy of the lateral pillars of the philthrum named as ‘pseudocleft’ is seen in about 54% cases(4).

The post auricular area had an overlying hemangiomatous skin, which had subsided since birth. This abnormal skin with or without sinus or fistulae is the pathognomonic malformation of the BOF syndrome. Other features are oligodontia, sparse hair and premature graying of hair. Skeletal defects are rare, those described being fifth finger clinodactyly, polydactyly and single palmar creases.

Severe brain malformations are rare, but cerebellar agenesis and mild hydrocephalous have been described. Pulmonic stenosis has not been described so far. Branchio-oto-renal syndrome has a considerable overlap with BOFS. The BOR gene has been mapped and named EYA 1 gene. The known genes of the EYA family are not involved in BOFS(5). Pediatricians must be aware of this syndrome as this is an autosomal dominant disorder and carries a 50% risk of recurrence, hence genetic counseling is important.

Seema Kapoor,
Nitin Kapur,
Division of Genetics,
Department of Pediatrics,
Maulana Azad Medical College,
New Delhi 110 002, India.
Correspondence:
Dr. Seema Kapoor,
M-439, Guru Harkrishan Nagar,
Paschim Vihar,
New Delhi 110 087, India.
E-mail: [email protected]

1. Lin AE, Gorlin RJ, Lurie IW, Brunner HG, vander Burgt I, Naumchick IV et al. Further delineation of the Branchio-oculo-facial syndromes. Am J Med Genet 1995; 56: 42-59.

2. Bennacceur S, Buisson T, Bertolus C, Couly G. Branchio-oculo-facial syndrome with cleft lip and bilateral dermal thymus. Cleft Palate Craniofac J 1998; 35: 454-459.

3. Raveh E, Papsin BC, Forte V. Branchio-oculo-facial syndrome. Int J Pediatr Otorhinolaryngol 2000; 53: 149-156.

4. Fujimoto A, Lipson M, LacroRV, Sheno NW, Boetler WD, Jones KL, et al. New Autosomal domonant branchio-oculo-facial syndrome. Am J Med Genet 1987; 27: 943-951.

5. Correa-Cerro LS, Kennerknecht I, Just W, Vogel W, Muller D. The gene for branchio-oculo-facial syndrome does not colocalize to the EYA 1-4 genes. J Med Genet 2000; 37: 620-623.