Bile duct paucity is part of the neonatal ichthyosis-sclerosing cholangitis phenotype

Neonatal ichthyosis-sclerosing cholangitis (NISCh) syndrome is a rare autosomal recessive disorder associated with scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. It is caused by homozygous mutations in the CLDN1 gene coding for the tight junction component claudin-1. Only five patients have been reported so far: four patients from two inbred Moroccan families, all carrying a dinucleotide deletion c.200_201delTT in the CLDN1 gene and a Swiss patient with a 1-bp deletion (c.358delG) in exon 2. Here, we report on three Moroccan brothers born of consanguineous parents (first cousins) presenting with ichthyosis, hypotrichosis and congenital paucity of bile ducts. In our patients, we found the same dinucleotide deletion (c.200_201delTT) in the CLDN1 gene that had been reported previously. In our view, this is suggestive of a founder effect. Interestingly, our patients presented not with sclerosing cholangitis but with congenital paucity of bile ducts. Although the two conditions cannot always be easily distinguished, we would suggest that paucity of bile ducts could be a manifestation of NISCh.