PLACK syndrome: A Rare Genetic Disorder
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PLACK (peeling skin, leuconychia, acral keratoses, cheilitis and knuckle pads) syndrome is a recently described, rare autosomal recessive genodermatosis for which the molecular basis has been identified as loss-of-function mutations in the CAST gene, which encodes the endogenous calpain inhibitor, calpastatin. Calpains play a role in regulating epidermal end differentiation, and increased levels arising from inactivating mutations in the CAST manifest with the hyperkeratosis and skin fragility observed in patients with PLACK syndrome.

Proband presented at 5 years of age with severe xerosis and skin blisters measuring 2–7 mm in size, which had been present since birth. Over the subsequent 2 years, further signs emerged with a bilateral painful angular cheilitis, punctate palmoplantar keratoderma (predominantly on the hands), follicular hyperkeratosis of the knees, nail thickening, marked scalp scaling and thickened skin over the knuckles. The evolution of the clinical findings raised the possibility of PLACK syndrome and prompted sequencing of the CAST gene. Birectional Sanger sequencing of the CAST gene was undertaken using primer pairs. This demonstrated a homozygous single nucleotide transversion, leading to a premature termination codon which was consistent with the clinical picture and confirmed PLACK syndrome.

This rare syndrome has only been recognized as a distinct clinical entity in recent years. Six homozygous nonsense mutations in CAST have previously been reported. The homozygous p.Gly191* mutation identified in our proband is novel, and expands the database of CAST mutations giving rise to PLACK syndrome.

This case demonstrates the typical clinical features of this newly identified genodermatosis, PLACK syndrome, which, with an estimated prevalence of less than 1 in 10,00,000 is extremely rare. In the case presented, the development of the classic phenotypic constellation prompted sequencing of the CAST gene and subsequent molecular confirmation of the diagnosis.

source: https://onlinelibrary.wiley.com/doi/full/10.1111/ced.14417
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