Abstract
Purpose :
The diagnostic yield of genetic testing in inherited retinal dystrophies (IRD) varies at different centers. This retrospective study evaluates the proportion of IRD patients seen at the Hospital for Sick Children (SickKids) who receive conclusive genetic test results. Our aim was to determine the yield of genetic testing for IRDs at SickKids over the span of 2 years and delineate which subgroups of IRD patients had a higher likelihood of having causative mutations identified.
Methods :
Patients who had been clinically evaluated and offered clinical genetic testing at the Ocular Genetics Clinic in Sickkids Hospital from January 2016 to December 2017 were included. Clinical diagnosis, genetic testing results and follow-up plan were obtained from the internal ocular genetic database and patient records. Results were categorized based on clinical diagnosis e.g. Lebers Congenital Amaurosis (LCA), Achromatopsia etc. Descriptive statistics were used to analyse the data.
Results :
The patient population included in the study was 647 individuals (419 probands, 228 relatives). Of the probands 255 (60.85%) were male and 162 (38.66%) were female. Among the probands 231 (55.13%) had causative mutations identified, 105 (25.05%) had VUS, 67 (15.99%) had a negative result, and the rest did not have testing done. Of all diagnoses, IRDs comprised more than 50% of cases. Among the subcategories based on clinical diagnoses, causative mutations were identified in 88.23% (15/17) of LCA patients and in 71.42% (10/14) of patients with achromatopsia. The number of patients who had no causative mutations identified were highest in the retinal dystrophies subcategory (34/268) at 12.68%.
Conclusions :
The systematic multidisciplinary approach to patient diagnosis and management at SickKids yields a higher rate of identifying causative mutations than has previously been described. This number will become higher as more VUSs become recategorized as pathogenic variants. The high yield of genetic tests for IRD will continue to improve and contribute positively to patient management.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.