Netherton syndrome is a rare autosomal recessive disorder characterized by the 
triad of ichthyosiform erythrodermia, typical hair dysplasia, and severe atopic 
features. The broad range of variable expression of this disease is well 
described and 20% of complications occur during the neonatal period such as 
hypernatremic dehydration, electrolyte imbalances, recurrent or severe 
infections, and failure to thrive. Mutation of the SPINK5 gene has been 
identified as disease-causing in Netherton syndrome, but the pathophysiology 
still remains unclear. Almost all SPINK5 mutations result in the absence of the 
serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes. 
In this study, we report on a severe form of Netherton syndrome observed in 
three patients within a large inbred Rom family. All of them died in the first 
months of life despite early treatment. They were found to be homozygous for the 
c.1431-12G>A SPINK5 gene mutation, which has not been associated with a lethal 
form of the disease thus far. This family illustrates the extreme phenotype of 
Netherton disease of neonatal onset. Molecular diagnosis allowed further genetic 
counseling and prenatal testing during other pregnancies.