Xp22.13 duplication causing Nance-Horan syndrome: case report

Nance-Horan syndrome (NHS) is a rare X-linked disorder caused by variants in the NHS gene on chromosome Xp22.13, characterized by congenital cataracts, dysmorphic facies, intellectual disability, and dental anomalies. Most pathogenic variants reported to date are protein‑truncating variations and large deletions of the NHS gene, while duplications of the NHS locus have been rarely described and never associated with a full syndromic presentation. We report the case of a 10-year-old male patient, with right visually significant sutural cataract and left visually insignificant partial sutural cataract, bilateral microcornea, and learning disabilities. His mother and maternal grandmother had sutural cataracts, and there was a family history of dental issues. NHS single gene analysis identified a partial duplication at Xp22.13. Only two duplications involving the NHS locus have been previously reported, and neither was associated with a conclusive NHS phenotype. This case represents, to the best of our knowledge, the first description of NHS caused by a simple partial duplication restricted to the NHS gene, expanding the mutational and phenotype spectrum of this rare disorder and suggesting that copy number gains should be considered in the genetic workup of patients with suspected NHS.