Prenatal and postnatal diagnosis of congenital ichthyosis: Three Asian-Indian cases

Congenital ichthyosis (CI) represents a heterogeneous group of inherited keratinization disorders that typically present at birth or in early childhood. While some forms are limited to cutaneous involvement, syndromic variants may also affect the liver, musculoskeletal system, and nervous system. The advent of next-generation sequencing has improved delineation of the genetic basis of CI, enabling precise diagnosis and genetic counseling. We report three children with CI evaluated at a tertiary care center. The first case was a 19-month-old girl with lamellar scaling, ectropion, strabismus, hepatosplenomegaly, and cytoplasmic vacuoles in neutrophils. Whole-exome sequencing (WES) confirmed Chanarin-Dorfman syndrome due to a homozygous ABHD5 pathogenic variant. She was managed with emollients, topical retinoids, dietary fat modification, and multidisciplinary support. The second case, a 2-year-old boy with diffuse scaling, growth failure, rickets, and developmental delay, had a pathogenic 15q11.2 microdeletion in addition to a homozygous NIPAL4 mutation on WES, consistent with autosomal recessive congenital ichthyosis. He received nutritional rehabilitation, skin-directed therapy, and genetic counseling. The third case involved a fetus with antenatally detected growth restriction, microcephaly, clubfeet, and ambiguous genitalia. Following termination, dysmorphic features and skeletal anomalies were noted. WES confirmed Neu-Laxova syndrome due to a homozygous PSAT1 nonsense mutation. This case series highlights the broad phenotypic and genotypic spectrum of congenital ichthyosis, ranging from multisystem lipid storage disorders to dual genetic diagnoses and lethal syndromic presentations. Detailed clinical evaluation combined with genomic diagnostics is critical for establishing an accurate diagnosis, guiding multidisciplinary management, and providing informed genetic counseling.