Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by multiple basal cell carcinomas and odontogenic keratocysts.
A characteristic appearance including facial milia, frontal bossing, wide nasal bridge, coarse facial features, high-arched eyebrows and palate, mandibular prognathism, and macrocephaly may be present. Palmar and plantar pits, skeletal abnormalities of the ribs, and vertebrae and ectopic calcification of the falx cerebri are often found and useful in diagnosis.
Individuals are also at increased risk for developing other cysts and neoplasms including medulloblastoma and cardiac and ovarian fibromas.
NBCCS is inherited in an autosomal dominant fashion, with approximately 70% to 80% of patients receiving an affected gene from a parent and the remaining 20% to 30% representing de novo mutations. Penetrance is near complete.
While other inherited disorders such as susceptibility to basal cell carcinoma (BCC), Bazex syndrome and Rombo syndrome should be considered in the setting of multiple BCCs, NBCCS should be highly suspected in cases of odontogenic keratocysts or early-onset medulloblastoma, see Table 113-1.
|Syndrome||Gene Symbol||Associated Findings|
Susceptibility to basal cell carcinoma
BCC1, BCC2, BCC3, BCC4, BCC5, BCC6
Basal cell carcinoma
Basal cell carcinoma, congenital hypotrichosis, follicular atrophoderma
Basal cell carcinoma, atrophoderma, milia, hypotrichosis, trichoepitheliomas, peripheral vasodilation with cyanosis
Multiple familial trichoepithelioma
Trichoepitheliomas that may degenerate into basal cell carcinoma
Trichoepitheliomas that may degenerate into basal cell carcinoma, cylindromas, and spiradenomas
Diagnostic Criteria and Clinical Characteristics
Diagnosis may be made in the presence of two major and one minor criterion or one major and three minor criteria.
Greater than five in a lifetime or one under age 30
Palmar or plantar pits
Two or more
Lamellar calcification of the falx or calcification of the falx at less than 20 years
First-degree relative with NBCCS
Congenital skeletal anomaly
Occipitofrontal head circumference greater than 97th percentile
Ovarian or cardiac fibromas
Lymphomesenteric or pleural cysts
Cleft lip or palate
Preaxial or postaxial polydactyly
Many patients have a characteristic appearance with coarse facial features, frontal bossing, high-arched eyebrows and palate, wide nasal bridge, mandibular prognathism, macrocephaly, and facial milia. Shoulders are downward sloping and some patients may be very tall.
Early skin lesions may have the appearance of nevi. Carcinomas are histologically indistinguishable from a typical BCC. These occur most frequently in the third and fourth decades of life, and are more common in individuals of lighter skin color and those with more exposure to ultraviolet light. However, approximately 10% of individuals with NBCCS never manifest BCCs.
Facial milia are present in 50% to 60% of patients. Skin tags may appear in childhood, especially around the neck, and are histologically similar to BCC. Meibomian cysts, sebaceous cysts, and dermoid cysts are frequent.
Keratocysts are cystic lesions of the bone lined with a thin, uniform layer of keratinized epithelium. Lesions are locally destructive and aggressive, leading to tooth disruption or jaw fracture if left untreated. Approximately 90% of those with NBCCS develop multiple odontogenic keratocysts and peak occurrence is within the second and third decades. Three-fourths occur in the mandible.
Pits are highly characteristic of NBCCS and useful in diagnosis, present in about 80% of those affected. They are more easily visualized after soaking the hands and feet in warm water for 10 to 15 minutes. Pits are shallow, 1 to 3 mm, white or pink depressions at areas of partial or complete absence of the stratum corneum.
Calcification of the falx cerebri, sella turcica, tentorium cerebelli, or petroclinoid ligament may take place; calcification of the falx is nearly always present after age 20. This is visible on skull x-rays.
Many patients demonstrate rib abnormalities such as bifid, splayed, extra or absent ribs. Bifid, wedged or fused vertebrae may also be present. Sprengel and pectus deformities are less common.
Cardiac fibromas occur in a small percentage of individuals with NBCCS and are generally present at the time of birth. These may lead to obstruction or conduction abnormalities.