Analysis of clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion.
10.3760/cma.j.cn112140-20211115-00953
- VernacularTitle:染色体16p11.2微缺失相关癫痫的临床与遗传学特点分析
- Author:
Hui Song WANG
1
;
Jie DENG
1
;
Xiao Hui WANG
1
;
Chun Hong CHEN
1
;
Xu WANG
1
;
Xiu Wei ZHUO
1
;
Li Fang DAI
1
;
Hua LI
1
;
Fang FANG
1
Author Information
1. Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
- Publication Type:Journal Article
- MeSH:
Child, Preschool;
Chromosomes;
DNA Copy Number Variations;
Electroencephalography;
Epilepsy/genetics*;
Female;
Humans;
Male;
Polymicrogyria/genetics*;
Retrospective Studies;
Seizures/genetics*
- From:
Chinese Journal of Pediatrics
2022;60(4):339-344
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion. Methods: The patients (n=10) with 16p11.2 microdeletion found in children with epilepsy treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2018 to January 2021 were collected. The clinical manifestations, gene variations and prognosis were analyzed retrospectively. Results: A total of 10 children's data were collected, including 5 male and 5 female. The onset age of epilepsy was 4.5 (4.1,5.0) months. Regarding the seizure types, 7 cases had focal seizures with secondary generalization, 2 cases had generalized seizures, and 1 case had tonic seizures and spasms. Nine cases had cluster seizure attacks and 3 cases had status epilepticus. Seven cases had focal or multifocal epileptiform discharges in interictal electroencephalogram (EEG), 3 cases had borderline or normal EEG. Brain magnetic resonance imaging showed polymicrogyria in 1 case, paraventricular leukomalacia in 1 case, delayed myelination of white matter in 3 cases, and no obvious abnormalities in the other 5 cases. The patients were followed up for 0.5-3.5 years, with 1-3 kinds of antiepileptic drugs taken orally. The case with polymicrogyria still had seizures, however the other 9 cases had seizures controlled. The age of the last seizure attack was 8 (6, 12) months. There were 6 cases with mental and motor developmental delay before epilepsy onset. During the follow-up, 7 cases were retarded to varying degrees, while 3 cases had normal development. Regarding the genetic detection methods, 7 cases underwent whole exome sequencing, 2 cases underwent whole genome copy number variation detection, and 1 case underwent whole genome sequencing. The length of the 16p11.2 deletion in 10 cases ranged from 525 to 951 kb, and all contained the PRRT2 gene intact. Six cases were de novo variants, 1 case was inherited from the mother who had a history of convulsions in early childhood, and the source of variant was not verified in 3 cases, none of whose parents had relevant phenotype. Conclusions: The epilepsy associated with 16p11.2 microdeletion is mainly induced by the heterozygous deletion of PRRT2 gene in this region, however the phenotype is usually severe, and often combined with developmental and epileptic encephalopathy. Detection of copy number variation should be emphasized in children whose etiology is considered genetic but second-generation sequencing result is negative.
