1. Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders
- Author
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Liping Zhang, Xu‐Ying Li, Fanxi Xu, Lehong Gao, Zhanjun Wang, Xianling Wang, Xian Li, Mengyu Liu, Junge Zhu, Tingyan Yao, Jing Ye, Xiao‐Hong Qi, Yaqing Wang, Guoguang Zhao, Chaodong Wang, and The Xuanwu Molecular Counselling Group for Neurogenetic Diseases
- Subjects
epilepsy ,epileptic encephalopathy ,genetic diagnosis ,multidisciplinary molecular consultation ,neurodevelopmental delay ,in ,Genetics ,QH426-470 - Abstract
Abstract Background Epilepsy (EP) is a common neurological disease in which 70–80% are thought to have a genetic cause. In patients with epilepsy, neurodevelopmental delay (NDD) was prevalent. Next generation of sequencing has been widely used in diagnosing EP/NDD. However, the diagnostic yield remains to be 40%–50%. Many reanalysis pipelines and software have been developed for automated reanalysis and decision making for the diseases. Nevertheless, it is a highly challenging task for smaller genetic centers or a routine pediatric practice. To address the clinical and genetic “diagnostic odyssey,” we organized a Multidisciplinary Molecular Consultation (MMC) team for molecular consultation for 202 children with EP/NDD patients referred by lower level hospitals. Methods All the patients had undergone an aligned and sequential consultations and discussions by a “triple reanalysis” procedure by clinical, genetic specialists, and researchers. Results Among the 202 cases for MMC, we totally identified 47 cases (23%) harboring causative variants in 24 genes and 15 chromosomal regions after the MMC. In the 15 cases with positive CNVs, 3 cases harbor the deletions or duplications in 16p11.2, and 2 cases for 1p36. The bioinformatical reanalysis revealed 47 positive cases, in which 12 (26%) were reported to be negative, VUS or incorrectly positive in pre‐MMC reports. Additionally, among 87 cases with negative cases, 4 (5%) were reported to be positive in pre‐MMC reports. Conclusion We established a workflow allowing for a “one‐stop” collaborative assessments by experts of multiple fields and helps for correct the diagnosis of cases with falsenegative and −positive and VUS genetic reports and may have significant influences for intervention, prevention and genetic counseling of pediatric epilepsy and neurodevelopmental disorders.
- Published
- 2023
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