Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children

LAI Chong-Yuan; CHEN Rui-Hua; ZHONG Chun-Lan; JI Ming-Ming; LI Bing-Fei

doi:10.7499/j.issn.1008-8830.2111110

PDF(514 KB)

Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (5) : 585-590. DOI: 10.7499/j.issn.1008-8830.2111110

CLINICAL RESEARCH

Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children

LAI Chong-Yuan, CHEN Rui-Hua, ZHONG Chun-Lan, JI Ming-Ming, LI Bing-Fei

Author information +

History +

Abstract

Objective To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children. Methods The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed. Results The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children. Conclusions 16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.

Key words

Epilepsy / 16p11.2 microdeletion / Whole exon sequencing technology / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LAI Chong-Yuan, CHEN Rui-Hua, ZHONG Chun-Lan, JI Ming-Ming, LI Bing-Fei. Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(5): 585-590 https://doi.org/10.7499/j.issn.1008-8830.2111110

References

1 蒋萍, 张桐, 汤继宏, 等. 新生突变的16p11.2微缺失综合征(附1例报告及文献复习)[J]. 中国临床神经科学, 2021, 29(3): 303-309.
2 Rein B, Yan Z. 16p11.2 copy number variations and neurodevelopmental disorders[J]. Trends Neurosci, 2020, 43(11): 886-901. PMID: 32993859. PMCID: PMC7606557. DOI: 10.1016/j.tins.2020.09.001.
3 Matsuzaki J, Berman JI, Blaskey L, et al. Abnormal auditory mismatch fields in children and adolescents with 16p11.2 deletion and 16p11.2 duplication[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2020, 5(10): 942-950. PMID: 32033921. DOI: 10.1016/j.bpsc.2019.11.005.
4 Blackmon K, Thesen T, Green S, et al. Focal cortical anomalies and language impairment in 16p11.2 deletion and duplication syndrome[J]. Cereb Cortex, 2018, 28(7): 2422-2430. PMID: 28591836. DOI: 10.1093/cercor/bhx143.
5 Bachmann-Gagescu R, Mefford HC, Cowan C, et al. Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity[J]. Genet Med, 2010, 12(10): 641-647. PMID: 20808231. DOI: 10.1097/GIM.0b013e3181ef4286.
6 Vlaskamp DRM, Callenbach PMC, Rump P, et al. PRRT2-related phenotypes in patients with a 16p11.2 deletion[J]. Eur J Med Genet, 2019, 62(4): 265-269. PMID: 30125676. DOI: 10.1016/j.ejmg.2018.08.002.
7 Kleinendorst L, van den Heuvel LM, Henneman L, et al. Who ever heard of 16p11.2 deletion syndrome? Parents' perspectives on a susceptibility copy number variation syndrome[J]. Eur J Hum Genet, 2020, 28(9): 1196-1204. PMID: 32415274. PMCID: PMC7608422. DOI: 10.1038/s41431-020-0644-6.
8 Kleinendorst L, Sno M, van Haelst MM. A girl with 16p11.2 deletion syndrome[J]. Ned Tijdschr Geneeskd, 2019, 163: D3441. PMID: 30945833.
9 Shinawi M, Liu P, Kang SH, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size[J]. J Med Genet, 2010, 47(5): 332-341. PMID: 19914906. PMCID: PMC3158566. DOI: 10.1136/jmg.2009.073015.
10 蔺朋武, 孟照琰, 冯暄, 等. 2例16p11.2微缺失综合征家系的临床表型及分子遗传学分析[J]. 兰州大学学报(医学版), 2021, 47(5): 81-85. DOI: 10.13885/j.issn.1000-2812.2021.05.014.
11 葛婷, 崔云, 肖咏梅, 等. 16p11.2缺失综合征1例并文献复习[J]. 中国循证儿科杂志, 2014, 9(6): 452-455. DOI: 10.3969/j.issn.1673-5501.2014.06.010.
12 Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 512-521. PMID: 28276062. PMCID: PMC5386840. DOI: 10.1111/epi.13709.
13 Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J]. Genet Med, 2020, 22(2): 245-257. PMID: 31690835. PMCID: PMC7313390. DOI: 10.1038/s41436-019-0686-8.
14 Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 522-530. PMID: 28276060. DOI: 10.1111/epi.13670.
15 李小燕. 再发性16p11.2微缺失在不明原因智力低下/发育迟缓患儿中的患病率和表型异质性研究[D]. 南昌: 南昌大学, 2015.
16 Zou D, Wang L, Liao J, et al. Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study[J]. Brain, 2021, 144(12): 3623-3634. PMID: 34145886. PMCID: PMC8719847. DOI: 10.1093/brain/awab233.
17 Bassuk AG, Geraghty E, Wu S, et al. Deletions of 16p11.2 and 19p13.2 in a family with intellectual disability and generalized epilepsy[J]. Am J Med Genet A, 2013, 161A(7): 1722-1725. PMID: 23686817. PMCID: PMC4169108. DOI: 10.1002/ajmg.a.35946.
18 Yang L, You C, Qiu S, et al. Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy[J]. Brain Behav, 2020, 10(5): e01597. PMID: 32237035. PMCID: PMC7218244. DOI: 10.1002/brb3.1597.
19 Weber A, K?hler A, Hahn A, et al. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome[J]. Neurogenetics, 2013, 14(3-4): 251-253. PMID: 24100940. DOI: 10.1007/s10048-013-0376-7.
20 Calame DJ, Xiao J, Khan MM, et al. Presynaptic PRRT2 deficiency causes cerebellar dysfunction and paroxysmal kinesigenic dyskinesia[J]. Neuroscience, 2020, 448: 272-286. PMID: 32891704. DOI: 10.1016/j.neuroscience.2020.08.034.
21 Chung WK, Roberts TP, Sherr EH, et al. 16p11.2 deletion syndrome[J]. Curr Opin Genet Dev, 2021, 68: 49-56. PMID: 33667823. DOI: 10.1016/j.gde.2021.01.011.
22 Cooper GM, Coe BP, Girirajan S, et al. A copy number variation morbidity map of developmental delay[J]. Nat Genet, 2011, 43(9): 838-846. PMID: 21841781. PMCID: PMC3171215. DOI: 10.1038/ng.909.