Familial progressive hyperpigmentation (FPH) is an autosomal dominant disorder characterized by hyperpigmented patches in the skin, which are present in early infancy and increase in size and number with age (summary by Wang et al., 2009).
... Familial progressive hyperpigmentation (FPH) is an autosomal dominant disorder characterized by hyperpigmented patches in the skin, which are present in early infancy and increase in size and number with age (summary by Wang et al., 2009). For a discussion of genetic heterogeneity of FPH, see FPH1 (614233).
Familial progressive hyperpigmentation was observed by Chernosky et al. (1971) in 4 individuals in 2 generations of a black family. It was characterized by patches of cutaneous hyperpigmentation which were present at birth and increased in size and ... Familial progressive hyperpigmentation was observed by Chernosky et al. (1971) in 4 individuals in 2 generations of a black family. It was characterized by patches of cutaneous hyperpigmentation which were present at birth and increased in size and number with age. Eventually large areas of skin became hyperpigmented. A mother had 2 affected children by different husbands. Rebora and Parodi (1989) traced the disorder through at least 4 generations of an Italian family. A discoloration had its onset on the external genitalia around the second month of life. There were several instances of male-to-male transmission. Debao and Ting (1991) examined 15 affected persons in 6 generations of a kindred of Han nationality living in China. The onset of the pigmentation was either at birth or in early infancy and consisted of irregular patches which increased with age in size, number, and confluence. Progression was rapid during childhood and slower during adolescence and resulted in extensive hyperpigmentation of the conjunctiva, face, neck, trunk, limbs, lips, oral mucosa, palms, and soles. Biopsies from hyperpigmented areas showed hyperkeratosis with marked increase in the amount of melanin in the epidermis, especially in the basal cell layer and at the tips of the rete ridges. The dermis appeared normal. In all, 21 persons in 6 generations were affected. The hyperpigmentation showed no whorls or streaks. Wang et al. (2009) followed up on a 6-generation Chinese family from Shandong province originally described by Debao and Ting (1991). All affected individuals manifested a pigmentation disorder without association of any other system disease. Hyperpigmentation was reported on hands, palms, limbs, conjunctive tissue of the face, neck, trunk, and soles. No affected member had skin cancer. The pattern of inheritance was autosomal dominant.
Wang et al. (2009) identified an asn36-to-ser (184745.0003) mutation in the KIT ligand gene in a 6-generation family segregating familial progressive hyperpigmentation. The mutation cosegregated with affected individuals and was not present in any unaffected members. Functional analysis ... Wang et al. (2009) identified an asn36-to-ser (184745.0003) mutation in the KIT ligand gene in a 6-generation family segregating familial progressive hyperpigmentation. The mutation cosegregated with affected individuals and was not present in any unaffected members. Functional analysis revealed that this is a gain-of-function mutation and that the presence of the mutant allele increased the content of melanin by 109% compared to wildtype KIT ligand in human melanoma cells. Tyrosinase (606933) activity was significantly increased in mutant compared to wildtype controls as well.