Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

Sofia Douzgou,Jamie M. Ellingford,Georgina Hall,Eva Lenassi,Panagiotis I. Sergouniotis,Jane L. Ashworth,William D. Newman,Vinod Sharma,Simon C. Ramsden,Susmito Biswas,Rachel L. Taylor,Claire L. Hardcastle,Jill Clayton-Smith,Graeme C. Black,Cecilia Fenerty,I. Chris Lloyd,Tracy A. Fletcher,Stuart Ingram

doi:10.1038/s41436-019-0722-8

Abstract

PurposeA key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs). MethodsTwo hundred one unrelated children (0–5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011–2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing. ResultsThe diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism). ConclusionGenetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

Highlights

Inherited eye disorders are an important cause of visual impairment in children and young adults.[1]
Genetic testing helped identify an etiological diagnosis in the majority of preschool children with inherited eye disorders (IEDs)
Diagnostic yield A probable molecular diagnosis was identified in 129/201 probands (64%); the diagnostic yield of genetic testing for each condition is shown in Table 1 and the genetic findings are presented in detail in Supplementary Table 1

Summary

Introduction

Inherited eye disorders are an important cause of visual impairment in children and young adults.[1] Prevalent subtypes include inherited retinal disease (IRD), pediatric cataracts, ocular anterior segment dysgenesis (ASD), and albinism. These conditions may manifest as isolated ophthalmic disorders (nonsyndromic forms) or as part of multisystemic syndromes that include extraocular features (syndromic forms).

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Conclusion