Table 1. Comparison of Diagnostic Criteria for Basal Cell Nevus Syndrome (BCNS) continued...
Rombo syndrome, a very rare genetic disorder associated with BCC, has been outlined in three case series in the literature.[114,115,116] The cutaneous examination is within normal limits until age 7 to 10 years, with the development of distinctive cyanotic erythema of the lips, hands, and feet and early atrophoderma vermiculatum of the cheeks, with variable involvement of the elbows and dorsal hands and feet. Development of BCC occurs in the fourth decade. A distinctive grainy texture to the skin, secondary to interspersed small, yellowish, follicular-based papules and follicular atrophy, has been described.[114,116] Missing, irregularly distributed and/or misdirected eyelashes and eyebrows are another associated finding.[114,115]
Bazex-Dupré-Christol syndrome, another rare genodermatosis associated with development of BCC, has more thorough documentation in the literature than Rombo syndrome. Inheritance is accomplished in an X-linked dominant fashion, with no reported male-to-male transmission.[117,118,119] Regional assignment of the locus of interest to chromosome Xq24-q27 is associated with a maximum LOD score of 5.26 with the DXS1192 locus.
Characteristic physical findings include hypotrichosis, hypohidrosis, milia, follicular atrophoderma of the cheeks, and multiple BCC, which manifest in the late second decade to early third decade. Documented hair changes with Bazex-Dupré-Christol syndrome include reduced density of scalp and body hair, decreased melanization, a twisted/flattened appearance of the hair shaft on electron microscopy, and increased hair shaft diameter on polarizing light microscopy. The milia, which may be quite distinctive in childhood, have been reported to regress or diminish substantially at puberty. Other reported findings in association with this syndrome include trichoepitheliomas, hidradenitis suppurativa, hypoplastic alae, and a prominent columella.[123,124]
Epidermolysis bullosa simplex, Dowling-Meara
A rare subtype of epidermolysis bullosa simplex (EBS), Dowling-Meara (EBS-DM), is primarily inherited in an autosomal dominant fashion and is associated with mutations in either keratin-5 (KRT5) or keratin-14 (KRT14). EBS-DM is one of the most severe types of EBS and occasionally results in mortality in early childhood. One report cites an incidence of BCC of 44% by age 55 years in this population. Individuals who inherit two EBS mutations may present with a more severe phenotype. Other less phenotypically severe subtypes of EBS can also be caused by mutations in either KRT5 or KRT14. Approximately 75% of individuals with a clinical diagnosis of EBS (regardless of subtype) have KRT5 or KRT14 mutations.
Characteristics of hereditary syndromes associated with a predisposition to BCC are described in Table 2 below.