Molecular Genetics & Genomic Medicine (Nov 2023)

Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders

  • 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,
  • The Xuanwu Molecular Counselling Group for Neurogenetic Diseases

DOI
https://doi.org/10.1002/mgg3.2243
Journal volume & issue
Vol. 11, no. 11
pp. n/a – n/a

Abstract

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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.

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