%0 Journal Article
%T Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders.
%A Zhang L
%A Li XY
%A Xu F
%A Gao L
%A Wang Z
%A Wang X
%A Li X
%A Liu M
%A Zhu J
%A Yao T
%A Ye J
%A Qi XH
%A Wang Y
%A Zhao G
%A Wang C
%A  
%J Mol Genet Genomic Med
%V 11
%N 11
%D 2023 Nov
%M 37489029
%F 2.473
%R 10.1002/mgg3.2243
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>All the patients had undergone an aligned and sequential consultations and discussions by a "triple reanalysis" procedure by clinical, genetic specialists, and researchers.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.