The patterns of birthmarks suggest a novel population of melanocyte precursors arising around the time of gastrulation

Abstract

SummarySystematic 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.

The biker‐glove pattern of congenital melanocytic nevi

“…The finding of a biker‐glove pattern in CMN lends support to this hypothesis which also noted that melanocyte migration in most CMN emanates from a central point in a circular field, perhaps due to melanocyte precursor division and passive diffusion . The patterns presented here correspond to the distal limb (or glove/stocking) field as described previously, with variable involvement of the digits and sparing of the finger/toe tips …”

“…Neither the segmental neural crest‐derived melanocyte precursors nor the newly described mesoderm‐derived melanocytes seem to supply the digital tips and nails . It therefore follows that those structures are supplied by a yet unidentified population of melanocyte precursors.…”

“…In 2018, Kinsler and Larue proposed that CMN arise from the mesoderm, from a population of melanocytes arising around the time of gastrulation, ultimately residing within the dermis . The finding of a biker‐glove pattern in CMN lends support to this hypothesis which also noted that melanocyte migration in most CMN emanates from a central point in a circular field, perhaps due to melanocyte precursor division and passive diffusion .…”

“…In recent years, important advances have been made in the understanding of CMN pathogenesis. The causal mutations of the majority of CMN have been identified, and recent data suggest the existence of two distinct melanocyte precursor populations leading to congenital pigmentary disease, implicating precursors derived from mesoderm in the patterning of most large CMN …”

Patterned cutaneous hypopigmentation phenotype characterization: A retrospective study in 106 children

“…B, Type 1b, broad bands along the lines of Blaschko. C, Type 2, blocklike pattern (also called checkerboard, flaglike or segmental pattern) . This pattern is characterized by unilateral of bilateral quadrilateral shapes with a sharp midline demarcation.…”