Inherited epidermal differentiation disorders (EDD) in pediatric patients from a single Italian referral Center

Inherited epidermal differentiation disorders (EDD) are a heterogeneous group of genetic skin diseases characterized by impaired epidermal differentiation and defective skin-barrier function. These conditions include congenital ichthyoses and palmoplantar keratoderma (PPK), which are particularly rare in the pediatric population and can present with evolving and, in mild forms, nonspecific or subtle clinical features, making early diagnosis challenging in children. A retrospective review was conducted on pediatric patients with a clinical and molecular diagnosis of EDD, who were evaluated at a single Italian referral center for rare skin disorders over a 12-month period. Data on phenotypic features, the underlying genetic defect, and dermatologic therapy were collected for three patients. Two patients were clinically and molecularly diagnosed with autosomal recessive congenital ichthyosis (ARCI) and carried homozygous variants in NIPAL4 and TGM1, respectively. A third female patient was found to harbor a homozygous c.82del(p.Cys28fs) variant in SLURP1, causing Mal de Meleda (MDM), a rare genodermatosis characterized by PPK.

This study describes three previously unreported pediatric patients with EDD evaluated at a single Italian specialized center. All patients presented with congenital and clinically heterogeneous dermatologic features, emphasizing the variability of these rare genodermatoses. Molecular analysis enabled prompt and accurate diagnosis, thereby supporting clinical management and treatment selection. Further pediatric case descriptions may help delineate the phenotypic spectrum of EDD, improve recognition by pediatricians, and reinforce key therapeutic principles.

• Inherited epidermal differentiation disorders (EDD) are a heterogeneous group of genetic skin diseases that can substantially impair quality of life. • Pediatric descriptions of these conditions, often based on single-center experiences, remain limited.

• The clinical and molecular findings of additional pediatric patients with EDD evaluated at an Italian referral center are reported. • This study contributes to the limited body of knowledge regarding the presentation of EDD during childhood.