Random Dermatology MCQ - Piebaldism

A newborn infant is noted to have a white forelock and well-demarcated, congenital, non-scaling hypopigmented macules on the ventral trunk and extremities. The patches remain stable throughout childhood. The parents report no history of seizures or developmental delay. Which of the following is the most likely genetic defect and the cell type primarily affected?

A) KIT mutation; melanocytes
B) MITF mutation; melanocytes
C) Hermansky-Pudlak syndrome gene mutation; melanosomes
D) Tyrosinase mutation; melanocytes
E) NF1 mutation; neural crest cells

Correct Answer: A) KIT mutation; melanocytes

Explanation

This presentation is classic for piebaldism, a rare, autosomal dominant disorder of melanocyte development.

Key Clinical Features of Piebaldism:

• White Forelock (Poliosis): A congenital, triangular or diamond-shaped patch of white hair in the frontal scalp. This is a hallmark feature.

• Cutaneous Depigmentation: Stable, well-demarcated, congenital, white macules and patches that are present at birth and do not change in size or shape.

• Characteristic Distribution: Typically involves the ventral trunk, mid-arms, and mid-legs, often with hyperpigmented macules within or at the border of the white patches.

• Stability: The lesions are non-progressive and remain unchanged throughout life.

• Absence of Systemic Features: Unlike Waardenburg syndrome, there is no associated sensorineural deafness or heterochromia iridis.

Genetic Defect and Pathophysiology:

• Gene: Mutations in the KIT proto-oncogene on chromosome 4q12.

• Cell Type Affected: Melanocytes derived from the neural crest.

• Mechanism: The KIT gene encodes a tyrosine kinase receptor for stem cell factor (SCF). This KIT/SCF signaling pathway is critical for the migration, proliferation, and survival of melanoblasts (melanocyte precursors) from the neural crest to the skin and hair follicles during embryogenesis.

• Result: Mutations in KIT lead to an absence of melanocytes in certain areas of the skin and hair, resulting in the characteristic congenital depigmentation.

Why Not the Other Options?

• (B) MITF mutation: Mutations in MITF (microphthalmia-associated transcription factor) can cause a rare form of Waardenburg syndrome type 2, which includes piebaldism-like depigmentation plus sensorineural hearing loss and heterochromia iridis.

• (C) Hermansky-Pudlak syndrome gene mutation: This affects melanosome and platelet dense granule formation, causing oculocutaneous albinism and a bleeding diathesis, not the distinct patterned depigmentation of piebaldism.

• (D) Tyrosinase mutation: Causes oculocutaneous albinism type 1, which presents with generalized hypopigmentation of skin, hair, and eyes, not the patterned depigmentation of piebaldism.

• (E) NF1 mutation: Causes neurofibromatosis type 1, which can feature café-au-lait macules and axillary freckling, but not the stable, congenital, ventral depigmentation of piebaldism.

Management:

• Reassurance about the benign, stable nature of the condition.

• Sun protection for depigmented areas to prevent sunburn and skin cancer.

• Cosmetic options: Camouflage makeup or, in selected cases, autologous melanocyte transplantation.

Note: Piebaldism is a disorder of melanocyte development, whereas vitiligo is an acquired disorder of melanocyte destruction. The key diagnostic clues are the congenital, stable, ventral distribution of depigmentation and the presence of a white forelock.