Piebaldism With Neurofibromatosis Type 1-Like Hyperpigmentation

Background Piebaldism is a rare autosomal dominant genodermatosis, manifesting as congenital and stable depigmentation of skin and white forelock. The depigmentation of skin has a characteristic distribution pattern that favors the central forehead, midfrontal portion of the scalp with a resultant triangular white forelock, central anterior trunk, and mid-extremities. It has been found to be associated with mutation in the KIT or SLUG gene. Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease. It is characterized clinically by Cafe-au-lait macules (CALMs), neurofibromas, freckling in the axillae and groin, Lisch nodules and bony defects. NF1 is caused by mutation of the NFI gene.Objective We collected a piebaldism pedigree, of which the proband manifested with typical lesion of piebaldism and hyperpigmentation of NFl-like. Molecular biological detection was performed in the pedigree to offer more information of gene mutation in piebaldism, to identify the relationship between mutation site and severity of clinical phenotype, and to investigate the relationship between piebaldism with NF1-like hyperpigmentation and NF1.Methods The piebaldism pedigree was investigated, the locations of lesions were recorded and pictures were taken. Polymerase chain reaction (PCR) and DNA sequencing were used to detect the mutation of KIT, SLUG, and NFI genes in patients of the pedigree and healthy adults as control group.Results Depigmentation of central forehead, central anterior trunk, and mid-extremities with a resultant triangular white forelock, associated with CALMs and intertriginous freckling were found in proband. A similar phenotype was confirmed in the son of proband. A heterozygous missense c.2431T>G mutation in exon 17 of KIT gene was found in proband, and no potentially pathogenic variant was identified in SLUG or NF1 gene. The same mutation was found in the affected son. No gene mutation was found in 100 unrelated control individuals, and the search in the database of 1000 Genomes Project suggests the mutation is not neutral polymorphism.Conclusion The heterozygous missense c.2431T>G mutation (p.F811V), codon of which is located in the center of tyrosine kinase domain, is the disease-causing mutation in the pedigree with piebaldism, which has not been reported previously. Severity of clinical phenotypecorrelates with the mutation site within the KIT gene; the most severe phenotypes usually result from mutations involving the intracellular tyrosine kinase domain. NF1-like hyperpigmentation seen in some piebaldism patients is part of pigmented anomaly in piebaldism, which does not necessarily represent coexistence of NF1.