Segregation of two variants suggests the presence of autosomal dominant and recessive forms of -related disease within the same family: expanding the phenotypic spectrum of Wolfram Syndrome.

BACKGROUND

was initially described as causative agent of autosomal recessive (AR) Wolfram syndrome, a childhood-onset disorder involving diabetes, optic atrophy, hearing loss and neurodegenerative features. However, the discovery of autosomal dominant (AD) disorders caused by this gene has resulted in clinical counselling and result interpretation challenges.

OBJECTIVE

We seek to report a family that appears to segregate dominant and recessive forms of -related disease.

METHODS/RESULTS: A 19-year-old woman presented with progressive childhood sensorineural hearing loss and recent optic atrophy, with biallelic mutations in : c.2486T>C (likely pathogenic) and c.2470G>A (uncertain significance). Her AC was normal. Her sister carried the same variants and had a similar phenotype. Their father carried c.2486T>C and was found to have mild-moderate hearing loss but no optic atrophy or neurological symptoms. The mother carried c.2470G>A and had a normal audiogram and ophthalmological exam. Providing anticipatory guidance for this family was difficult given the phenotypic variability of -related disorders and the uncertainty surrounding whether the inheritance pattern was AR or AD.

CONCLUSION

The clinical correlation of the variants identified in this family suggests an AR Wolfram-like syndrome, without the typical diabetes mellitus or diabetes insipidus nor neurological decline. To our knowledge, this is a novel -related phenotype.