Abstract
Purpose :
In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like Syndrome (WLS) is a rare, autosomal dominant disease caused by mutations in the WFS1 gene. It presents with optic atrophy, sensorineural hearing loss and diabetes mellitus. Here, we present a case of WLS without endocrine manifestations caused by a heterozygous missense WFS1 variant (c.2508G>T, p. Lys826Asn).
Methods :
Single case with a heterozygous WFS1 variant (c.2508G>T, p.Lys836Asn), ophthalmic examination, multimodal imaging and genetic testing will be discussed.
Results :
A 28-year-old Greek male was referred to our clinic for evaluation of bilateral optic nerve atrophy of unknown cause. Review of systems revealed bilateral sensorineural hearing loss for which he requires hearing aids. Family history was significant for early-onset severe hearing loss in his mother. The patient had best corrected visual acuity of 20/30 and 20/40 in the right and left eye, respectively. Pupillary responses, intraocular pressures and anterior segment exam were unremarkable. Fundus exam revealed normal appearance of the retina and bilateral tilted and pale optic nerves. Testing showed reduced contrast, color and depth perception. Visual fields showed supero-temporal and infero-nasal defects in both eyes. Optical coherence tomography revealed retinal nerve fiber layer global thinning in both eyes measuring 49 and 46 microns in the right and left eye, respectively. In addition, ganglion cell layer thickness was significantly reduced OU. MRI of the head and orbits was unremarkable. Blood work for toxic, infectious and nutritional causes of optic neuropathy were normal. Genetic testing was negative for mutations in OPA1, OPA3 and LHON panel; however, it revealed a heterozygous missense variant in WFS1 gene (c.2508G>T, p.Lys836Asn). To date, this variant is not present in gnomAd database and predicted to be pathogenic by in silico tools. His fasting blood glucose was 96mL/dL and hemoglobin A1C was 4.9%.
Conclusions :
We present deep phenotyping of a previously described WFS1 variant (c.2508G>T, p. Lys836Asn) (Hogewind B. F., Pennings R. J., Hol F. A., et al. Autosomal dominant optic neuropathy and sensorineual hearing loss associated with a novel mutation of WFS1. Molecular Vision. 2010;16:26–35.). Our findings confirm this heterozygous variant in WFS1 as a cause of optic atrophy and hearing loss without neurologic, cardiac or endocrine problems.
This is a 2021 ARVO Annual Meeting abstract.