Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy

• Published in: Scientific reports Vol. 14; no. 1; pp. 22956 - 9
• Main Authors: de Muijnck, Cansu, Haer-Wigman, Lonneke, van Everdingen, Judith A. M., Lushchyk, Tanya, Heutinck, Pam A. T., van Dooren, Marieke F., Kievit, Anneke J. A., Verhoeven, Virginie J. M., Simon, Marleen E. H., Wasmann, Rosemarie A., Notting, Irene C., De Baere, Elfride, Walraedt, Sophie, De Zaeytijd, Julie, Van den Broeck, Filip, Leroy, Bart P., Boon, Camiel J. F., van Genderen, Maria M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 692/1807; 692/1807/1482; 692/308; 692/700/139; Adolescent; Adult; Aged; Anterior chamber; Atrophy; Child; Color vision; Diabetes mellitus; DOA; Extremities; Eye diseases; Female; Genotype & phenotype; GTP Phosphohydrolases - genetics; Hearing loss; Humanities and Social Sciences; Humans; Inherited optic neuropathy; Lamination; Male; Membrane Proteins - genetics; Middle Aged; multidisciplinary; Mutation; OPA1; Optic atrophy; Optic Atrophy, Autosomal Dominant - genetics; Optic Atrophy, Autosomal Dominant - pathology; Optic neuropathy; Phenotype; Phenotypes; Science; Science (multidisciplinary); Visual evoked potentials; WFS1; Wolfram Syndrome - genetics; Young Adult; Optic atrophy; Inherited optic neuropathy; OPA1; WFS1; DOA
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-74364-x

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1 -associated optic atrophy (AD WFS1 -OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1 -gene. WFS1 -associated diseases, or ‘wolframinopathies’, exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1 -associated disease, the combination of OA and hearing loss (HL), clinically resembles the ‘plus’ phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1 -OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.