Nevoid Basal Cell Carcinoma Syndrome

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].

Excerpt

Clinical characteristics: Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs), usually from the third decade onward. Many individuals have a recognizable appearance with macrocephaly, frontal bossing, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in 90% of affected individuals by age 30 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals, respectively. Approximately 5% of all children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor), generally the desmoplastic subtype. The risk of developing medulloblastoma is substantially higher in individuals with an SUFU pathogenic variant (33%) than in those with a PTCH1 pathogenic variant (<2%). Peak incidence is at age one to two years. Life expectancy in NBCCS is not significantly different from average.

Diagnosis/testing: The diagnosis of NBCCS is established in a proband who fulfills proposed diagnostic clinical criteria. Identification of a heterozygous germline pathogenic variant in PTCH1 or SUFU by molecular genetic testing establishes the diagnosis if clinical features are inconclusive.

Management: Treatment of manifestations: Best provided by specialists experienced with the condition; avoidance of direct sun exposure through the use of complete sunblock and covering of exposed skin with long sleeves, high collars, and hats; early treatment of BCCs to ensure complete eradication of aggressive BCCs and to preserve normal tissue to prevent disfigurement; sonic hedgehog inhibitors such as vismodegib to treat severe BCCs; jaw keratocysts usually require surgical excision; treatment of medulloblastoma per neurosurgeon/oncologist.

Surveillance: Monitor head circumference throughout childhood; ophthalmology evaluations per ophthalmologist; feeding, hearing, and speech evaluation as needed in those with a history of cleft lip/palate; clinical exam for scoliosis as needed; skin examination at least annually; orthopantogram every 12-18 months beginning at age eight years to identify jaw keratocysts; developmental assessment and physical examination every six months until age five years due to increased risk for medulloblastoma; brain MRI in those with SUFU-related NBCCS every three to four months until age three years, every six months until age five years, annually until age eight years for medulloblastoma, and then every three to five years beginning at age 30 years for meningioma; ovarian ultrasound in women at age 18 years.

Agents/circumstances to avoid: Radiotherapy if there are alternative treatments, especially in childhood; diagnostic radiographs should be used sparingly; direct sun exposure should be limited, as excessive sun exposure increases the likelihood of developing BCCs.

Evaluation of relatives at risk: Because of the need for surveillance for complications of NBCCS (medulloblastoma in children; jaw keratocysts and BCCs in adults) and the need to avoid radiographs and sun exposure, clarification of the genetic status of at-risk relatives, including children, is appropriate.

Genetic counseling: NBCCS is inherited in an autosomal dominant manner. Approximately 70%-80% of individuals with NBCCS have an affected parent and about 20%-30% have NBCCS as the result of a de novo pathogenic variant. Each child of an individual with NBCCS has a 50% chance of inheriting the disorder. If the NBCCS-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for NBCCS are possible.

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