Ophthalmic, systemic, and genetic characteristics of patients with Wolfram syndrome

To evaluate the ophthalmic, systemic, and genetic characteristics of patients with Wolfram syndrome.

In total, 13 patients with suspected or clinically diagnosed Wolfram syndrome underwent ophthalmic and systemic examinations and genetic analyses for Wolfram syndrome between August and October 2018.

The mean age of the subjects was 24.2 ± 7.1 years, of which 5 (38.5%) subjects were male and 8 (61.5%) were female. The mean best-corrected visual acuity ranged from counting fingers to 20/40, with a mean of 20/250 (1.10 ± 0.69 logarithm of the minimum angle of resolution). Dyschromatopsia was present in all patients (100%). There was a severe decrease in the average peripapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thicknesses (54.7 ± 6.5 and 51.9 ± 4.8 µm, respectively). Optical coherence tomography angiography showed significantly lower whole-image, inside disk, and peripapillary vessel densities in the patients with Wolfram syndrome than in the healthy controls (p < 0.001 for all). All patients who underwent genetic analyses had mutations in the WFS1 gene. Moreover, two novel mutations, p.Met623Trpfs*2 (c.1867delA) and p.Arg611Profs*9 (c.1832_11847del16) at exon 8, were detected. The frequency of systemic findings was as follows: optic atrophy (100%), diabetes mellitus (92.3%), central diabetes insipidus (38.5%), sensorineural hearing loss (38.5%), and presence of urological (30.8%), psychiatric (30.8%), and neurological (23.1%) diseases.

Wolfram syndrome is a rare genetic disorder that can be associated with severe ophthalmic and systemic abnormalities. All patients who present with unexplained optic atrophy should be evaluated for Wolfram syndrome, even if they do not have diabetes mellitus because optic atrophy can sometimes manifest before diabetes mellitus.