Protean cutaneous manifestation caused by ABCA12 variants: erythrokeratodermia variabilis-like ichthyosis and unique palmoplantar keratoderma

Abstract

ABCA12 is crucial for skin barrier function and traditionally linked to severe congenital ichthyosis, such as harlequin ichthyosis. However, its genotype-phenotype relationship may be more nuanced. Using whole-exome sequencing and Sanger sequencing, we identified four cases of mild ichthyosis with biallelic ABCA12 pathogenic variants. In addition to a milder phenotype, the palmoplantar keratoderma (PPK) in these cases had a distinct “mosaic-tile like” pattern. Two cases with missense variants in the N-terminus of ABCA12 also presented an annular ichthyosis pattern resembling erythrokeratodermia variabilis et progressiva (EKVP). Our findings suggest a correlation between ABCA12 missense variant location and clinical presentation, expanding the phenotype spectrum associated with ABCA12 variants and highlighting the potential for annular patterns or “mosaic-tile like” PPK in these patients.