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Real-world clinical presentation and genetic spectrum of young bilateral cataract patients presenting to an ocular genetics service

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First Author: S.Bell UK

Co Author(s):    S. Malka   C. Lloyd   M. Moosajee              

Abstract Details

Purpose:

Childhood cataract affects 2.5-3.5 per 10,000 of UK children with a genetic mutation identified in 50-90% of bilateral cases. However, diagnosis is challenging as cataracts can also manifest in adolescence and early adulthood in isolation, as part of a complex ocular phenotype or with systemic features. Comprehensive panel testing of the genes known to cause cataracts has been shown to streamline care pathways and alter clinical outcomes for these patients. We investigate our real-world experience of consecutive bilateral cataract patients (0-25 years) presenting to the ocular genetics service over a 44 month period.

Setting:

The ocular genetics service at Moorfields Eye Hospital (NHS) Foundation Trust.

Methods:

A retrospective case-note review of consecutive patients who attended MEH between January 2017-August 2020 was performed. Patients were eligible if they were less than 26 years old at age of cataract diagnosis and had received a genetic result or attended a review appointment at MEH within this timeframe. Molecular testing was performed both in the clinical and research setting using next-generation sequencing panel testing, whole genome sequencing as part of the UK Genomics England 100,000 Genomes project or single gene genetic testing via Sanger sequencing in cases of aniridia (identification of PAX6 mutation) or for confirmatory testing of research findings.

Results:

Fifty-four patients from 44 unrelated families were identified, median age 13.5 years (range 1 to 68 years), median age at diagnosis 43.9 months IQR (53-4264 days); 40.7% female and 46.3% Caucasian. Overall, 37 patients from 28 families (63.6%) were genetically solved, with 27 disease-causing variants in 22 genes; the most common was CRYBB2. Eight novel variants were discovered. Associated diagnoses were retinal dystrophies in 5 (17.9%) and aniridia in 3 (10.7%) families. Bilateral cataracts were the presenting feature in 30.4% (7/23) of either complex or syndromic cases, isolated cataract patients were 13.6 years younger (rank-sum Z=4.809, P =.0000).

Conclusions:

We expand the mutational spectrum for known cataract genes in young patients and highlight their extreme heterogeneity and the challenges faced in establishing a molecular diagnosis. We show how a genetic diagnosis can direct individual care pathways, including support in family planning and the potential to prevent significant systemic morbidity and mortality in syndromic patients. Despite genetic eye diseases affecting 1 in 1000 people worldwide, ophthalmic genomics is still considered a niche area. We highlight the importance of genetic testing in young cataract patients and the benefit of integration of genetic and genomics into UK mainstream ophthalmology.

Financial Disclosure:

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