Abstract
Purpose :
Heterozygous variants in WFS1 are associated with a Wolfram- like syndrome characterised by sensorineural hearing loss, optic atrophy and diabetes mellitus. A previous study described outer plexiform layer (OPL) lamination in dominant WFS1 disease. In this report two further patients are described.
Methods :
This was a retrospective case study of two probands from two families with detailed clinical phenotyping including ophthalmic examination, optic nerve and retinal imaging, and neuroimaging. Molecular investigations included targeted Sanger sequencing and next generation gene panel sequencing.
Results :
Two female patients with a background of congenital, severe sensorineural hearing loss, were incidentally found aged 10 years and 16 years to have optic disc pallor, with slightly reduced visual acuity (0.2-0.3 logMAR) and reduced color vision. Optical coherence tomography (OCT) of the nerve fiber layer identified severe generalised thinning. OCT of the macula demonstrated a linear splitting abnormality of the OPL within the central macula. Neuroimaging confirmed no intracranial cause of optic neuropathy.
In both probands, heterozygous variants were found in WFS1, specifically c.937T>C (p.His313Tyr) and c.2590G>A (p.Glu864Lys), both previously reported in affected patients. After identification of the optic neuropathy, diabetic screening was performed confirming diabetes mellitus in one proband.
Conclusions :
In optic atrophy, OCT macula may reveal a pathognomonic OPL lamination that is associated with dominant WFS1 variants.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.