Abstract
Purpose :
Purpose: The purpose of this study is to describe the genotype and phenotypes in a cohort of patients with presumed inherited optic atrophy.
Methods :
A retrospective review of the New Zealand Database of Inherited Retinal and Optic nerve disease to identify patients with inherited optic atrophy. A cohort of 67 patients from 55 families who presented to the Eye Clinic, and were recruited between January 1997 to August 2022 . Comprehensive clinical examination included vision, colour vision, ocular exam, imaging, and electrophysiology in some individuals. Additional testing variably included audiology, diabetic profiling and neurological examination. Family members were recruited and examined if possible. Candidate gene sequencing and next generation sequencing using an ocular gene panel were performed. In a small number of unsolved families, whole exome sequencing was performed.
Results :
A cohort of 67 patients (26 female, 41 male) from 55 families were recruited. All patients had presumed optic atrophy with typically temporal disc pallor and retinal nerve fibre layer thinning. Molecular diagnosis was achieved in 46 individuals from 35 families. Disease causing variants in OPA1 accounted for 22 cases in 16 families, including biallelic Behr disease in 2 patients. This was followed by mitochondrial disease (LHON), WFS1, ACO2, OPA3, ECHS1 and RTN4IP1. In one patient the ocular diagnosis changed due to disease associated variant in CACNAF1.
Conclusions :
The inherited group of optic atrophies are a heterogenous group of disorders as a result of retinal ganglion cell loss, however genotyping identifies the reasonably high prevalence of syndromic disease, particulary Wolfram syndrome. In this study causative variants were detected in 63.6% of patients . The genotypic spectrum associated with optic atrophy in a NZ population also includes ECHS1, a metabolic disorder in predominantly Samoan individuals, potentially modifiable with diet, along with ACO2-dominant optic atrophy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.