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  Disease summary:

  
  
  
  
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    Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by multiple basal cell carcinomas and odontogenic keratocysts.

    
    
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    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.

    
    
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    Individuals are also at increased risk for developing other cysts and neoplasms including medulloblastoma and cardiac and ovarian fibromas.

  
  
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  Hereditary basis:

  
  
  
  
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    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.

  
  
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  Differential diagnosis:

  
  
  
  
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    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.

Diagnostic Criteria for Nevoid Basal Cell Carcinoma Syndrome

Diagnosis may be made in the presence of two major and one minor criterion or one major and three minor criteria.

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  Major criteria:

  
  
  
  
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    Multiple BCCs

    
    
    
    
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      Greater than five in a lifetime or one under age 30

    
    
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    Odontogenic keratocyst

    
    
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    Palmar or plantar pits

    
    
    
    
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      Two or more

    
    
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    Ectopic calcification

    
    
    
    
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      Lamellar calcification of the falx or calcification of the falx at less than 20 years

    
    
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    First-degree relative with NBCCS

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  Minor criteria:

  
  
  
  
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    Congenital skeletal anomaly

    
    
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    Macrocephaly

    
    
    
    
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      Occipitofrontal head circumference greater than 97th percentile

    
    
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    Ovarian or cardiac fibromas

    
    
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    Childhood medulloblastoma

    
    
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    Lymphomesenteric or pleural cysts

    
    
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    Cleft lip or palate

    
    
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    Preaxial or postaxial polydactyly

    
    
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    Ocular anomalies

Clinical Characteristics

Appearance

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.

Basal Cell Carcinomas

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.

Other Skin Findings

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.

Odontogenic Keratocysts

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.

Palmar and Plantar Pits

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.

Ectopic Calcification

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.

Congenital Skeletal Anomalies

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 Fibroma

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.