Dataset Information

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study.

ABSTRACT: In recent years, genetic techniques of diagnosis have shown rapid development, resulting in a modified clinical approach to many diseases, including neurological disorders. Movement disorders, in particular those arising in childhood, pose a diagnostic challenge. First, from a purely phenomenological point of view, the correct clinical classification of signs and symptoms may be difficult and require expert evaluation. This is because the clinical picture is often a mixture of hyperkinetic and hypokinetic disorders, and within hyperkinetic movement disorders, combined phenotypes are not unusual. Second, although several genes that cause movement disorders in children are now well-known, many of them have only been described in adult populations or discovered in patients after many years of disease. Furthermore, diseases that alter their mechanisms from childhood to adulthood are still little known, and many phenotypes in children are the result of a disruption of normal neurodevelopment. High-throughput gene screening addresses these difficulties and has modified the approach to genetic diagnosis. In the exome-sequencing era, customized genetic panels now offer the ability to perform fast and low-cost screening of the genes commonly involved in the pathogenesis of the disease. Here, we describe a 3-year study using a customized gene panel for pediatric-onset movement disorders in a selected cohort of children and adolescents. We report a satisfying diagnostic yield, further confirming the usefulness of gene panel analysis.

SUBMITTER: Graziola F

PROVIDER: S-EPMC6828958 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study.

Graziola Federica F Garone Giacomo G Stregapede Fabrizia F Bosco Luca L Vigevano Federico F Curatolo Paolo P Bertini Enrico E Travaglini Lorena L Capuano Alessandro A

Frontiers in genetics 20191029

In recent years, genetic techniques of diagnosis have shown rapid development, resulting in a modified clinical approach to many diseases, including neurological disorders. Movement disorders, in particular those arising in childhood, pose a diagnostic challenge. First, from a purely phenomenological point of view, the correct clinical classification of signs and symptoms may be difficult and require expert evaluation. This is because the clinical picture is often a mixture of hyperkinetic and h ...[more]

PMID: 31737037

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Project description:Epilepsy is one of the most common childhood-onset neurological conditions with a genetic etiology. Genetic diagnosis provides potential for etiologically-based management and treatment. Existing research has focused on early-onset (<24 months) epilepsies; data regarding later-onset epilepsies is limited. The goal of this study was to determine the diagnostic yield of a clinically available epilepsy panel in a selected pediatric epilepsy cohort with epilepsy onset between 24-60 months of life and evaluate whether this approach decreases the age of diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2). Next-generation sequencing (NGS)-based epilepsy panels, including genes associated with epileptic encephalopathies and inborn errors of metabolism (IEMs) that present with epilepsy, were used. Copy-number variant (CNV) detection from NGS data was included. Variant interpretation was performed per American College of Medical Genetics and Genomics (ACMG) guidelines. Results are reported from 211 consecutive patients with the following inclusion criteria: 24-60 months of age at the time of enrollment, first unprovoked seizure at/after 24 months, and at least one additional finding such as EEG/MRI abnormalities, speech delay, or motor symptoms. Median age was 42 months at testing and 30 months at first seizure onset; the mean delay from first seizure to comprehensive genetic testing was 10.3 months. A genetic diagnosis was established in 43 patients (20.4%). CNVs were reported in 25.6% diagnosed patients; 27.3% of CNVs identified were intragenic. Within the diagnosed cohort, 11 (25.6%) patients were diagnosed with an IEM. The predominant molecular diagnosis was CLN2 (14% of diagnosed patients). For these patients, diagnosis was achieved 12-24 months earlier than reported by natural history of the disease. This study supports comprehensive genetic testing for patients whose first seizure occurs ≥ 24 months of age. It also supports early application of testing in this age group, as the identified diagnoses can have significant impact on patient management and outcome.

Dataset Information

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study.

Publications

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study.

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