Diagnosis: Piebaldism

The most prominent and common feature of piebaldism is a white forelock directly above the forehead, often with a triangular shape, in an area that is melanocyte-free. Named for the black-and-white-feathered magpie and the bald eagle, piebaldism was known to the Romans. It is one of the first genetic disorders for which a pedigree was presented. The disorder occurs in 1-2.5 of every 10,000 newborns. A Wood’s lamp will identify the depigmented patch at the hairline. Skin biopsy finds no melanocytes. A family history will likely be positive.

Piebaldism is a congenital leukoderma that is inherited in an autosomal dominant pattern. In some patients, white macules also manifest on eyebrow and eyelash hair either continuously or discontinuously with the white forelock. Roughly symmetrical white macules can also appear on the face (particularly the chin), trunk, legs, and arms (hands and feet are not usually affected) on the ventral surface of the body. In an occasional patient, the white macules have brown or black borders. The macules also contain islands of normal, brown, or black skin. These must be distinguished from café-au-lait macules, which in numbers of six or more would indicate neurofibromatosis.

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Piebaldism is due to an absence of melanocytes in affected skin and hair follicles resulting from mutations of the c-kit proto-oncogene (>75% of cases) and HIKE and SLUG gene defects (>25%). These mutations lead to defective melanoblast proliferation, survival, and migration from the neural crest during development. The c-kit proto-oncogene encodes for the cell-surface tyrosine kinase receptor, the ligand of which is a stem and mast cell growth factor. The nature of the c-kit mutation defines the manifestations of the piebaldism. The SLUG gene (known officially as SNAI2) is crucial for the normal development of neural crest-derived cells. SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. Waardenburg syndrome is a systemic disease characterized by a white forelock along with iris heterochromia, lateral displacement of inner canthi, and deafness, which can be caused by PAX3, MITF, and SOX10 (endothelin-B receptor [ENDRB]) gene mutations. HIKE is a kinase inactivator and likely affects tyrosine kinase in patients with piebaldism.

Piebaldism usually remains static throughout the patient’s life. Some authorities categorize piebaldism with disease types featuring partial albinism, but piebaldism manifests with normal eye pigmentation. Genetic analysis of a mother and daughter with progressive piebaldism revealed a novel mutation in the c-kit gene. This newly described phenotype with melanocyte instability leads to advancing loss of pigmentation and the progressive appearance of hyperpigmented macules.

Piebaldism patients have almost no systemic complications. Woolf syndrome is piebaldism associated with deafness, but whether this is true piebaldism or some other disease is un-clear. Piebaldism with lifelong severe constipation has been reported. Mouse models of piebaldism include gut pathology commonly proved by histology, but histologic specimens of human guts in piebaldism rarely show pathologic changes. Homozygosity in piebald trait was noted with almost no pigmentation of the skin and hair, blue irises, and deafness.

The differential diagnosis of piebaldism is defined by other conditions that have white forelocks, including Woolf syndrome, Vogt-Koyanagi-Harada syndrome, and Waardenburg syndrome. Genetic conditions reported with concurrent piebaldism include Rubinstein-Taybi syndrome, fragile X syndrome, Brown-Séquard syndrome, congenital dyserythropoietic anemia type II, and neurofibromatosis 1. White forelock has been suggested as an early sign of tuberous sclerosis. Graft-versus-host reaction affecting lesional skin but not normal skin has been seen in a patient with piebaldism.

Piebaldism appears unresponsive to medical or light treatment. Attempts to darken the depigmented skin have not been effective. Micrografts with pigmented skin have been used. Dermabrasion followed by application of thin split-skin grafts has been tried, with residual leukodermic patches treated
using a minigrafting method. Additional irradiation with UVA was provided. This new combined approach led to 95%-100% repigmentation of the leukoderma. Permanent repigmentation of piebaldism by erbium:yttrium-aluminum-garnet laser and autologous cultured epidermis has been reported. Cosmetics and dyes may help mask the physical signs of this disorder. Patients should use sunscreens in depigmented areas.

Believing his forelock made him distinctive, our patient chose not to be treated. Genetic testing was not done.

Dr. Scheinfeld is assistant clinical professor of dermatology at Columbia University in New York City, where he has a private practice.