Progressive symmetrical erythrokeratoderma associated with biallelic <i>PNPLA1</i> variants

We describe three kindreds with progressive symmetrical erythrokeratoderma associated with recessive PNPLA1 variants, expanding the clinical spectrum of patatin-like phospholipase domain-containing protein 1 (PNPLA1)-related epidermal differentiation disorders. Affected individuals exhibited distinctive symmetrical 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.