Peeling Skin, Leukonychia, Acral Punctate Keratoses, Cheilitis and Knuckle Pads (PLACK) Syndrome: An Updated Review of Cases and Identification of a Recurrent CAST Variant in Two Patients

Pediatr Dermatol. 2025 Nov-Dec;42(6):1239-1247. doi: 10.1111/pde.15987. Epub 2025 May 19.

Abstract

Peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) syndrome (OMIM616295) is an exceptionally rare autosomal recessive genodermatosis caused by loss-of-function pathogenic variants in the CAST gene, encoding calpastatin. A total of 19 cases have been described in 12 articles, among families with unique de novo genetic variants of CAST. We describe two pediatric PLACK cases with a homozygous loss-of-function CAST variant (c.571G>T, p.Gly191Ter) which represents the only recurrent genetic variant of PLACK syndrome reported in the literature.

Keywords: PLACK; blistering; calpastatin; cheilitis; keratoses; leukonychia; peeling skin syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cheilitis* / diagnosis
  • Cheilitis* / genetics
  • Child
  • Child, Preschool
  • Dermatitis, Exfoliative* / diagnosis
  • Dermatitis, Exfoliative* / genetics
  • Female
  • Humans
  • Hypopigmentation* / diagnosis
  • Hypopigmentation* / genetics
  • Keratoderma, Palmoplantar* / genetics
  • Male
  • Nail Diseases* / genetics
  • Skin Diseases / congenital
  • Skin Diseases, Genetic

Supplementary concepts

  • Peeling Skin Syndrome
  • Peeling skin syndrome, acral type