Progressive symmetric erythrokeratoderma associated with biallelic PNPLA1 variants

We describe three kindreds with progressive symmetric erythrokeratoderma (PSEK) associated with recessive PNPLA1 variants, expanding the clinical spectrum of PNPLA1-related epidermal differentiation disorders. Affected individuals exhibited distinctive symmetric plaques with patterned sparing, contrasting with the generalized scaling typical of PNPLA1-associated autosomal recessive congenital ichthyosis. These findings highlight genotype-phenotype variability within PNPLA1 disease and support a role for lipid pathway-specific modifiers in shaping epidermal differentiation disorder phenotypes.