Clinical and genetic findings in 13 Chinese children with keratinopathic ichthyosis.

Importance: Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the , , or genes. In KPI, the relationship between genotype and phenotype is complex.

Objective: To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.

Methods: Clinical data were collected from 13 children diagnosed with KPI, and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel, and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.

Results: Genetic analysis identified missense mutations in either or in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis. A missense hotspot mutation in was identified in one patient with superficial epidermolytic ichthyosis. Additionally, two truncation mutations in were detected, leading to the development of generalized ichthyosiform erythroderma. Ear malformation and ectropion at birth, scalp involvement, and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.

Interpretation: We analyzed the genotype-phenotype correlations in KPI, revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics. Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.