PLACK syndrome resulting from a novel homozygous variant in CAST

Abstract

Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM 616295) is a recently described form of peeling skin syndrome (PSS). It is an autosomal recessive condition and has been shown to result from loss-of-function mutations in CAST, the gene encoding calpastatin, a specific inhibitor of calpains, which function as calcium-dependent cysteine proteases. 1,2 To date, six homozygous pathogenic variants in CAST gene (c.424A > T, c.607dup, c.1750delG, c.461dupGCAT, c.544G > T, c.507_508insA) have been associated with PLACK syndrome. 2-5 2 | C A S E REP ORT A 5-year-old girl, born to consanguineous parents, was referred for evaluation of skin fragility. Dry skin was noted at birth and at 6 months of age, she developed erythematous, itchy, eczematous patches on face, arms, and lower limbs. At 12 months, she was admitted with Staphylococcus aureus bullous impetigo, and a keratosis pilaris-like eruption was observed on the arms, abdomen, and legs. By 18 months, punctate keratoderma developed on the palms and plantar feet and became extremely troublesome, with resultant difficulty walking. The patient also began walking on tiptoes at this

Knuckle lesions in inherited and acquired disorders

“…Other abnormalities described in various reports include follicular hyperkeratosis, facial telangiectasia, woolly hair, and sparse eyebrows and eyelashes. [ 16 17 ]…”

Novel nonsense CAST mutation in two siblings with PLACK syndrome

“…The clinical and molecular findings of these subjects and the present case are summarized in Table 1. 1,[3][4][5][6][7][8] With this case report, we aim to contribute to the literature by expanding the pathogenic variant database and presenting the clinical findings.…”