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Phenotypic and Genetic Complexity in Pediatric Movement Disorders
The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198294/ https://www.ncbi.nlm.nih.gov/pubmed/35719373 http://dx.doi.org/10.3389/fgene.2022.829558 |
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author | Kim, Min-Jee Yum, Mi-Sun Seo, Go Hun Ko, Tae-Sung Lee, Beom Hee |
author_facet | Kim, Min-Jee Yum, Mi-Sun Seo, Go Hun Ko, Tae-Sung Lee, Beom Hee |
author_sort | Kim, Min-Jee |
collection | PubMed |
description | The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate the clinical benefit of WES as a diagnostic tool in a pediatric cohort. We evaluated 75 patients with diverse single or combined movement phenomenologies using WES. WES identified 42 variants in 37 genes (56.0%). The detection rate was highest in patients with dystonia (11/13, 84.6%), followed by ataxia (21/38, 55.3%), myoclonus (3/6, 50.0%), unspecified dyskinesia (1/4, 25.0%), tremor (1/1, 100%), respectively. Most genetically diagnosed patients (90.5%) were affected by other neurologic or systemic manifestations; congenital hypotonia (66.7%), and epilepsy (42.9%) were the most common phenotypes. The genetic diagnosis changed the clinical management for five patients (6.7%), including treatments targeting molecular abnormalities, and other systemic surveillance such as cancer screening. Early application of WES yields a high diagnostic rate in pediatric movement disorders, which can overcome the limitations of the traditional phenotype-driven strategies due to the diverse phenotypic and genetic complexity. Additionally, this early genetic diagnosis expands the patient’s clinical spectrum and provides an opportunity for tailored treatment. |
format | Online Article Text |
id | pubmed-9198294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91982942022-06-16 Phenotypic and Genetic Complexity in Pediatric Movement Disorders Kim, Min-Jee Yum, Mi-Sun Seo, Go Hun Ko, Tae-Sung Lee, Beom Hee Front Genet Genetics The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate the clinical benefit of WES as a diagnostic tool in a pediatric cohort. We evaluated 75 patients with diverse single or combined movement phenomenologies using WES. WES identified 42 variants in 37 genes (56.0%). The detection rate was highest in patients with dystonia (11/13, 84.6%), followed by ataxia (21/38, 55.3%), myoclonus (3/6, 50.0%), unspecified dyskinesia (1/4, 25.0%), tremor (1/1, 100%), respectively. Most genetically diagnosed patients (90.5%) were affected by other neurologic or systemic manifestations; congenital hypotonia (66.7%), and epilepsy (42.9%) were the most common phenotypes. The genetic diagnosis changed the clinical management for five patients (6.7%), including treatments targeting molecular abnormalities, and other systemic surveillance such as cancer screening. Early application of WES yields a high diagnostic rate in pediatric movement disorders, which can overcome the limitations of the traditional phenotype-driven strategies due to the diverse phenotypic and genetic complexity. Additionally, this early genetic diagnosis expands the patient’s clinical spectrum and provides an opportunity for tailored treatment. Frontiers Media S.A. 2022-06-01 /pmc/articles/PMC9198294/ /pubmed/35719373 http://dx.doi.org/10.3389/fgene.2022.829558 Text en Copyright © 2022 Kim, Yum, Seo, Ko and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Kim, Min-Jee Yum, Mi-Sun Seo, Go Hun Ko, Tae-Sung Lee, Beom Hee Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title | Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title_full | Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title_fullStr | Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title_full_unstemmed | Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title_short | Phenotypic and Genetic Complexity in Pediatric Movement Disorders |
title_sort | phenotypic and genetic complexity in pediatric movement disorders |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198294/ https://www.ncbi.nlm.nih.gov/pubmed/35719373 http://dx.doi.org/10.3389/fgene.2022.829558 |
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