Clinical Spectrum and Genetic Diagnosis of 54 Consecutive Patients Aged 0-25 with Bilateral Cataracts.

Suzannah Bell,Samantha Malka,Ian Christopher Lloyd,Ian Christopher Lloyd,Mariya Moosajee,Mariya Moosajee,Mariya Moosajee,Mariya Moosajee

doi:10.3390/genes12020131

Abstract

Childhood cataract affects 2.5–3.5 per 10,000 children in the UK, with a genetic mutation identified in 50–90% of bilateral cases. However, cataracts can also manifest in adolescence and early adulthood in isolation, as part of a complex ocular phenotype or with systemic features making accurate diagnosis more challenging. We investigate our real-world experience through a retrospective review of consecutive bilateral cataract patients (0–25 years) presenting to the ocular genetics service at Moorfields Eye Hospital between 2017 and 2020. Fifty-four patients from 44 unrelated families were identified, with a median age of 13.5 years (range 1 to 68 years) and a median age at diagnosis of 43.9 months IQR (1.7–140.3 months); 40.7% were female and 46.3% were Caucasian. Overall, 37 patients from 27 families (61.4%) were genetically solved (50%) or likely solved (additional 11.4%), with 26 disease-causing variants (8 were novel) in 21 genes; the most common were crystallin genes, in 8 (29.6%) families, with half occurring in the CRYBB2 gene. There was no significant difference in the molecular diagnostic rates between sporadic and familial inheritance (P = 0.287). Associated clinical diagnoses were retinal dystrophies in five (18.5%) and aniridia in three (11.1%) families. Bilateral cataracts were the presenting feature in 27.3% (6/22) of either complex or syndromic cases, and isolated cataract patients were 11.5 years younger (rank-sum Z = 3.668, P = 0.0002). Prompt genetic investigation with comprehensive panel testing can aid with diagnosis and optimise management of cataract patients.

Highlights

Cataract is a leading cause of avoidable visual impairment and blindness in both adults and children worldwide [1,2]
We report our real-world clinical experience of children and young adults presenting with cataracts to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust (MEH), which oversees the care of the largest number of genetic eye disease patients of any one site in the United Kingdom, and discuss the impact of genetic testing in this cohort
Thirty-one families received genetic testing via whole-genome sequencing (WGS), 8 received targeted panel sequencing, and 5 received single-gene Sanger sequencing

Summary

Introduction

Cataract is a leading cause of avoidable visual impairment and blindness in both adults and children worldwide [1,2]. In the UK, cataract affects 2.5–3.5 per 10,000 children, most within the first year of life [3]. It is a highly heterogenous disease with a broad aetiology including congenital infections (Toxoplasma gondii, Syphilis, Varicella-Zostervirus, Parvovirus B19, Coxsackievirus, Rubella, Cytomegalovirus, Herpes Simplex Virus I and II), trauma or radiation, previous ocular surgery or exposure to steroid medications. Hereditary cataracts can present in later adolescence or early adulthood either in isolation, as part of a complex ocular phenotype (e.g., with retinal dystrophies, anterior segment dysgenesis [ASD], and aniridia) or in association with systemic disorders (syndromic, e.g., cerebrotendinous xanthomatosis [CTX]) [6,7]

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Conclusion