Generalized Cutaneous Hyperpigmentation and Lentigines due to KIT Variant

Abstract

Activating KIT mutations are a rare cause of progressive hyperpigmentation and lentigines, with or without gastrointestinal stromal tumors (GISTs) , and effective treatments for the pigmentary phenotype remain limited. We report a family with generalized hyperpigmentation and lentigines carrying a germline KIT variant together with a missense variant in SASH1, another melanogenesis-related gene. The affected individuals showed marked clinical improvement following treatment with imatinib mesylate. Functional analyses further suggested that the SASH1 variant may modify KIT-associated melanogenesis.