Congenital cataracts in two siblings with Wolfram Syndrome

Abstract

Background: Wolfram syndrome is characterized by optic atrophy, insulin dependent diabetes mellitus, diabetes insipidus and deafness. There are several other associated conditions reported in the literature, but congenital or early childhood cataracts are not among them.

Materials and methods: Observational case series with confirmatory genetic analysis.

Results: A pair of siblings, followed over 17 years, who manifest congenital or early childhood cataracts, diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. They are both compound heterozygotes for mutations (V415 deletion and A684V substitution) in the WFS1 gene. Their father has congenital sensorineural hearing loss and developed optic atrophy. He is heterozygous for A684V in WFS1.

Conclusions: Wolfram syndrome should be in the differential diagnosis of genetic syndromes associated with congenital and early childhood cataracts. Here, we report on a mother who is a phenotypically normal carrier of an autosomal recessive Wolfram syndrome gene, and a father who has some of the findings of the syndrome and carries a single mutation that appears to be responsible for his hearing loss and optic atrophy. Their 2 children are compound heterozygotes and manifest the full Wolfram syndrome, in addition to cataracts.

KEYWORDS::

• Congenital cataracts
• Wolfram syndrome
• WFS1
• DIDMOAD (Diabetes, insipidus, diabetes mellitus, optic atrophy and deafness)

ACKNOWLEDGMENTS

This work was partially funded by an unrestricted grant from Research to Prevent Blindness, INC. New York, NY.

This work was also partially funded by grant DC00161 from NIDCD/NIH to M.L.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.