Genetic insights into neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome

Abstract Background Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome is a rare autosomal recessive syndrome due to mutations in the claudin-1 gene (CLDN1). Defective expression of claudin-1 protein manifests with involvement of the liver and skin. Phenotypic expression of the disease varies from cholangitis resolving on supportive management to severe liver damage requiring liver transplantation. Case presentation We hereby discuss an Indian infant presenting with neonatal cholestasis and ichthyosis, carrying a novel nonsense mutation in exon 3 of the CLDN1 gene (p.Pro154LeufsTer2). We also report a striking association between NISCH syndrome and hyperferritinemia; the pathophysiology for the same is yet to be elucidated. The patient’s clinical condition improved after supportive management, including vitamin supplementation, ursodeoxycholic acid, and emollients. Conclusion Awareness, early diagnosis, genotype-phenotype correlation, and timely and appropriate management are key to the prognostication of the patient.