Striking contiguous depigmentation across the lower limbs in piebaldism and its implications for understanding melanocytic migration and development

Piebaldism is an uncommon autosomal dominantly inherited pigment anomaly characterized by a congenital white forelock and leukoderma on the frontal scalp, forehead, ventral trunk and extremities. It is caused by a loss-of-function mutation in the KIT gene. Genetic analyses reveal a consistent genotype-phenotype relationship in piebaldism. However, recently reported cases of piebaldism that are milder or severer than genetically expected indicate that other factors, such as a modifier gene of MC1R, influence skin and hair color. The KIT ligand/KIT that triggers the Ras/mitogen-activated protein kinase signaling pathway play essential functions in the migration, proliferation, survival, melanogenesis and melanosome transfer of the melanocytes. We summarize current research progress in piebaldism and related disorders. © 2012 Japanese Dermatological Association.

Summary Systematic work in the mouse and chicken has mapped out two neural crest‐derived pathways of melanocyte precursor migration. With these in mind, this study reappraises the patterns of congenital pigmentary disorders in humans and identifies three recurrent patterns consistent across genetically different diseases. Only two of these are seen in diseases known to be melanocyte cell‐autonomous. The segmental pattern correlates well with the classical dorsolateral population from animal studies, demonstrating respect of the midline, cranio‐caudal axial mixing, unilateral migration and involvement of key epidermally derived structures. Importantly however, the melanocyte precursors responsible for the non‐segmental pattern, which demonstrates circular, bilateral migration centred on the midline, and not involving key epidermally derived structures, have not been identified previously. We propose that this population originates around the time of gastrulation, most likely within the mesoderm, and ultimately resides within the dermis. Whether it contributes to mature melanocytes in non‐disease states is not known; however, parallels with the patterns of acquired vitiligo would suggest that it does. The third pattern, hypo‐ or hyperpigmented fine and whorled Blaschko's lines, is proposed to be non‐cell‐autonomous.