Familial progressive hyper- and hypopigmentation and malignancy in two families with new mutations in KITLG

Clin Exp Dermatol. 2015 Dec;40(8):860-4. doi: 10.1111/ced.12702. Epub 2015 Jul 14.

Abstract

Background: Familial progressive hyper- and hypopigmentation (FPHH) is an autosomal dominant skin condition presenting in childhood with generalized macular dyspigmentation, usually reported in patients of East Asian origin. It overlaps phenotypically with other dyschromatoses, but can now be distinguished by mutations in the KIT ligand gene (KITLG).

Aim: We report two unrelated white families with similar phenotypic presentations of FPHH developing in early childhood in several generations.

Methods: Sanger sequencing of the exons and flanking introns of KITLG was performed.

Results: This identified a new heterozygous missense mutation in each family (p.Thr34Asn and p.Val37Gly, respectively). Of the six affected individuals examined by us, two had cancer: a 62-year-old man in family 1 had developed two primary melanomas and a pharyngeal carcinoma, and a 42-year-old woman in family 2 had developed thyroid carcinoma. All had unusually sparse lateral eyebrows, a finding not previously reported in this condition.

Conclusions: We summarize the genetic spectrum of the dyschromatoses and discuss a possible increased risk of malignancy in FPHH.

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Exons
  • Female
  • Humans
  • Hyperpigmentation / genetics*
  • Hypopigmentation / genetics*
  • Introns
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Neoplasms / complications
  • Pedigree
  • Stem Cell Factor / genetics*

Substances

  • Stem Cell Factor