Exome sequencing and electro-clinical features in pediatric patients with very early-onset retinal dystrophies: A cohort study
| Autor: | D. Colavito, Agnese Suppiej, V. Maritan, C. Ceccato, I. Cermakova, A. Leon |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Socio-culturale Nystagmus Vision impairment Cohort Studies 03 medical and health sciences 0302 clinical medicine 030225 pediatrics Retinal Dystrophies Exome Sequencing medicine Electroretinography Humans Exome sequencing Infant Genetic Association Studies medicine.diagnostic_test business.industry Childhood blindness General Medicine medicine.disease Very early onset Child Preschool Pediatrics Perinatology and Child Health Cohort Mutation Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Cohort study |
| Zdroj: | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 31 |
| ISSN: | 1532-2130 |
| Popis: | Inherited retinal dystrophies (IRDs) are a major cause of childhood blindness. Timely diagnosis requires a high level of clinical suspicion from both neurologists and ophthalmologists and is increasingly important given recent advancements in gene therapy. We focused our study on genotype-phenotype associations in very early-onset forms of retinal dystrophy, the least well characterized and most challenging diagnostic subgroup.From January 12, 2015 to March 31, 2017, we prospectively performed whole exome sequencing targeted on the phenotype of non-syndromic IRDs and phenotype characterization in a cohort of 68 children affected by very early-onset inherited retinal dystrophies, defined by the onset before five years of age. Phenotype parameters included age at onset, clinical presentation, ophthalmic evaluation, electrophysiological patterns and clinical course.A genetically confirmed diagnosis was achieved in 50 out of 60 (83%) families. The median age at onset was 4 months (6 m in 70%,2 y in 82% of the cases). Clinical presentation was associated with visual loss and nystagmus in the majority of patients. Three (CNGB3, CNGA3 and CACNA1F) out of 22 genes considered pathogenic in the cohort, accounted for 51% of all IRD's, all within the class of stationary IRDs.This study reports on the largest cohort of very early-onset retinal dystrophies, including a description of electroretinography patterns. The electro-clinical phenotype coupled with genetic diagnosis provided additional clues for child neurologists dealing with low vision and nystagmus in infancy. A high level of clinical suspicion improves the diagnosis with important implications for the future of the affected child. |
| Databáze: | OpenAIRE |
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