Branchiooculofacial Syndrome

Excerpt

Clinical characteristics: The branchiooculofacial syndrome (BOFS) is characterized by: branchial (cervical or infra- or supra-auricular) skin defects that range from barely perceptible thin skin or hair patch to erythematous "hemangiomatous" lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include ocular hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called "pseudocleft lip") with or without cleft palate, upper lip pits, and lower facial weakness (asymmetric crying face or partial 7th cranial nerve weakness). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.

Diagnosis/testing: The diagnosis is based on clinical findings and confirmed with the identification of a heterozygous pathogenic variant in TFAP2A.

Management: Treatment of manifestations: In general, children with BOFS should be managed by a multispecialty team including, for example, craniofacial specialists, plastic surgeons, otolaryngologists, and speech therapists. Small, linear or superficial branchial skin defects may heal spontaneously; however, some require surgical intervention. Anophthalmia or severe microphthalmia may require a conformer (a structure, usually plastic, inserted into the eye socket to encourage its growth); nasolacrimal duct stenosis or atresia often requires surgery. It is recommended that cleft lip be repaired by an experienced pediatric plastic surgeon. Lesser forms of cleft lip ("pseudocleft") may need surgical correction.

Surveillance: Monitor for changes related to the major findings over time as directed by the team of specialists.

Genetic counseling: BOFS is inherited in an autosomal dominant manner. De novo pathogenic variants are observed in 50%-60% of affected individuals. Each child of an individual with BOFS has a 50% chance of inheriting the pathogenic variant. Once the TFAP2A pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.