Lentiginosis, Inherited Patterned

O'Neill and James (1989) described autosomal dominant transmission of a pigmentary pattern characterized by facial, lip, extremity, buttock, and palmoplantar small, discrete hyperpigmented macules. None of the patients had lesions of the oral mucosa or internal organ system abnormalities. Thus, the disorder could be distinguished from the Peutz-Jeghers syndrome (175200), the centrofacial lentiginosis syndrome (151000), the Carney syndrome (160980) and the LEOPARD syndrome (151100), all of which have associated internal abnormalities. Although all the patients were of African extraction, it is unlikely that this trait occurs only in blacks. The pedigrees of 2 families showed extensive multigeneration involvement with numerous instances of male-to-male transmission.

Xing et al. (2005) reported a 4-generation Chinese family transmitting generalized lentiginosis as an autosomal dominant trait. Affected individuals had small brown macules on the face, extremities, and trunk, particularly noticeable on sun-exposed areas. The macules ranged in color from dark brown to black and ranged in size from a few mm to 1 cm in diameter. The palms, soles, and buccal mucosa were not affected. The lesions, which did not darken with sun exposure or lighten during the winter, first appeared at age 5 to 7 years; although they persisted throughout life, they faded in later years. The affected individuals had no hypopigmented macules or noncutaneous abnormalities.

Mapping

Xing et al. (2005) performed a genomewide linkage search in a 4-generation Chinese family segregating generalized lentiginosis as an autosomal dominant trait and localized the familial locus to chromosome 4q21.1-q22.3, with a maximum 2-point lod score of 3.01 for D4S395 and D4S423 (theta = 0.0). Multipoint analysis yielded a maximum lod score of 5.08 between markers D4S395 and D4S1563 and haplotype construction showed strong evidence of linkage in a region of 20 Mb flanked by markers D4S2915 and D4S1560 on chromosome 4q21.1-q22.3.