Next Generation Sequencing in presumptive diagnosis of syndromes in childhood retinal dystrophies - case series from India

Purpose

Childhood onset retinal dystrophies are heterogeneous group of diseases that include Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa, early onset retinitis pigmentosa (EORP) and Severe Early Childhood Onset Retinal Dystrophy (SECORD) and can present either as an isolated condition or with associated non-ocular features. Genetic testing aids in the differential diagnosis of these conditions, for monitoring and timely management of the systemic manifestations. In this study, we present a case series of childhood onset retinal dystrophies where genetic testing has aided in the diagnosis of syndromic form of inherited retinal degenerations (IRD).

Methods

Patients (N = 10) underwent complete ophthalmic examination including slit lamp biomicroscopy and dilated indirect ophthalmoscopy. ERG, fundus photograph and Optical Coherence Tomography was done for all patients if the child cooperated for the same. This was followed by targeted re-sequencing of IRD gene panel, on the Illumina Hiseq 2500 platform. Clinical follow up for other associated systemic features was advised based on the genetic results, for patients who were asymptomatic at the time of genetic diagnosis. The patients were monitored for the same periodically.

Results

Mutations were identified in IQCB1, ALMS1, SLC19A2, CNNM4, and VPS13B genes suggested associated syndromes. In all these cases, the ocular phenotype was the first presentation in early infancy and genetic testing for IRD genes suggested syndromic disease. The patients could hence be followed up appropriately for other manifestations.

Conclusions

Molecular diagnosis has helped in identifying the associated syndrome in these patients with childhood retinal dystrophies who were asymptomatic for some of the non-ocular features at the time of genetic testing. The patients can be benefitted by frequent clinical surveillance with a scope for effective and timely management of the systemic features wherever applicable.