Lethal Form of Netherton Syndrome in a Consanguineous Multiplex Family

This study reported on a severe form of Netherton syndrome in a large inbred family, where three neonatal cases were observed, all resulting in death despite early intensive care. The patients were homozygous for the c.1431-12G > A mutation in the SPINK5 gene, a mutation previously not associated with lethal outcomes. Netherton syndrome is an autosomal recessive disorder characterized by ichthyosiform erythrodermia, hair dysplasia, and severe atopic features, with a 20% rate of potentially lethal neonatal complications. The absence of the LEKTI protein, due to SPINK5 mutations, contributes to the disease, but the exact pathophysiology and variability in disease expression remained unclear. Molecular diagnosis facilitated prenatal testing and genetic counseling for future pregnancies.