Clinical characteristics: 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, cataract, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include dolichocephaly, 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 weakness of cranial nerve VII). 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 of BOFS is established in a proband with characteristic clinical findings and a heterozygous pathogenic variant in TFAP2A identified by molecular genetic testing.

Management: Treatment of manifestations: In general, children with BOFS should be managed by a multispecialty team including craniofacial specialists, plastic surgeons, otolaryngologists, and speech-language therapists. Small, linear, or superficial branchial skin defects may heal spontaneously; however, some require surgical intervention. Treatment of ophthalmic manifestations is per pediatric ophthalmologist. Nasolacrimal duct stenosis or atresia often requires surgery. Anophthalmia or severe microphthalmia may require a conformer (a structure, usually plastic, inserted into the eye socket to encourage its growth). It is recommended that cleft lip be repaired by an experienced pediatric plastic surgeon. Nasal tip abnormalities, lesser forms of cleft lip ("pseudocleft"), and malformed pinnae may need surgical correction. Standard treatments for hearing loss, renal malformations, dental manifestations, and congenital heart defects. Treatment of sensory, psychologic, and developmental challenges with supportive therapies.

Surveillance: Ophthalmology examination and vision assessment as recommended by ophthalmologist; audiology evaluation as recommended by otolaryngologist and/or audiologist; at each visit assess for a recurrent urinary tract infection suggestive of vesicoureteral reflux, assess teeth for size, number, carries, and malocclusion, and assess for new cysts; developmental and behavioral assessment annually or as needed; monitor for signs of low self-esteem and other psychological issues at each visit in older children as they enter adolescence.

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 and preimplantation genetic testing are possible.