Gaouzi Zainab, Belkhayat Aziza, Takki Zahra Chebihi, Lachraf Hind, Diawara Idrissa, Kriouile Yamna
Mohammed VI University of Sciences and Health, Mohammed VI Higher Institute of Biosciences and Biotechnologies (UM6SS), Casablanca, Morocco.
Mohammed VI Center for Research and Innovation (CM6RI), Rabat Morocco.
PLoS One. 2025 May 19;20(5):e0324177. doi: 10.1371/journal.pone.0324177. eCollection 2025.
Pediatric neurological disorders are a diverse group of conditions affecting the nervous system in children, often challenging to diagnose due to their nonspecific and overlapping clinical features. Advances in molecular diagnostics, particularly whole exome sequencing (WES), have significantly improved the identification of genetic causes, enabling precise diagnoses and personalized treatments. This study explores the application of WES in diagnosing pediatric neurological disorders within Moroccan childrens with undiagnosed or challenging pediatric neurological conditions to uncover genetic causes of complex pediatric neurological conditions unresolvable by traditional diagnostic methods. The study included 188 pediatric patients with complex neurological conditions from the Children's Hospital of Rabat who underwent exome sequencing to investigate suspected genetic causes. WES revealed a diagnostic yield of 45%, identifying conditions such as intellectual disabilities, hereditary metabolic disorders and epilepsies. It also uncovered neurodevelopmental and neurodegenerative disorders, neuromuscular diseases, and genetic syndromes. A total of 157 variants were detected: 34% were classified as pathogenic, 28.5% as likely pathogenic, and 37.5% as variants of uncertain significance (VUS). These findings underscore the utility of WES as a robust diagnostic tool, providing insights into genetic causes and enabling tailored treatment strategies. They also highlight the importance of expanding genetic research to improve diagnostic accuracy and clinical management of pediatric neurological disorders.
小儿神经系统疾病是影响儿童神经系统的多种病症，由于其临床特征不具特异性且相互重叠，往往难以诊断。分子诊断技术的进步，尤其是全外显子组测序（WES），显著提高了对遗传病因的识别能力，从而实现精准诊断和个性化治疗。本研究探讨了WES在诊断摩洛哥患有未确诊或具有挑战性的小儿神经系统疾病的儿童中的应用，以揭示传统诊断方法无法解决的复杂小儿神经系统疾病的遗传病因。该研究纳入了188名来自拉巴特儿童医院的患有复杂神经系统疾病的儿科患者，他们接受了外显子组测序以调查疑似遗传病因。WES的诊断率为45%，确定了智力残疾、遗传性代谢疾病和癫痫等病症。它还发现了神经发育和神经退行性疾病、神经肌肉疾病以及遗传综合征。总共检测到157个变异：34%被分类为致病性变异，28.5%为可能致病性变异，37.5%为意义未明的变异（VUS）。这些发现强调了WES作为一种强大诊断工具的实用性，为遗传病因提供了见解，并实现了量身定制的治疗策略。它们还凸显了扩大基因研究以提高小儿神经系统疾病诊断准确性和临床管理的重要性。
