PLACK syndrome is a rare autosomal recessive syndrome characterized by generalized peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads. The predominant clinical feature of PLACK syndrome in infancy is skin fragility with early-onset angular cheilitis. In early childhood, further signs such as punctate palmoplantar keratoderma, follicular hyperkeratosis, nail thickening, and marked scalp scaling may develop.

PLACK is caused by a loss-of-function mutation of the CAST gene that encodes calpastatin, the endogenous calpain inhibitor. Calpains, which are calcium-dependent cysteine proteases, help to regulate epidermal end differentiation and proteolytic pathways within the skin. The premature stop codon created by this nonsense mutation may lead to impaired keratinocyte adhesion and increased keratinocyte apoptosis.

The 12 patients with PLACK syndrome documented in the literature come from several ethnic backgrounds, including Chinese, Nepalese, and European, Tunisian, Arab, Turkish, Saudi, and Afghan. While many of these patients have consanguineous parents, a heterogeneous case has also been reported. The progression of PLACK syndrome varies among documented cases. One patient experienced significant improvement in their skin by age 11 years and no longer experiences pain, discomfort, or related functional problems. However, PLACK syndrome has been noted with additional features, including proximal lower limb weakness and abnormal gait; tooth decay; alopecia areata; woolly hair and sparse eyelashes; conjunctival injection and asthma; and cerebral atrophy with mild muscle involvement.