Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2022, Vol. 18 ›› Issue (03): 307 -314. doi: 10.3877/cma.j.issn.1673-5250.2022.03.009

Original Article

Atypical benign familial neonatal epilepsy: a case report and literature review

Junjie Ning1,2, Lina Qiao1,2,()   

  1. 1Department of Pediatric Intensive Care Unit, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2NHC Key Laboratory of Chronobiology (Sichuan University), Chengdu 610041, Sichuan Province, China
  • Received:2021-12-01 Revised:2022-05-15 Published:2022-06-01
  • Corresponding author: Lina Qiao
  • Supported by:
    Central Government Fund of Guiding Local Scientific and Technological Development for Sichuan Province(2021ZYD0105)
Objective

To explore the clinical features, lineage identification and gene mutation analysis of children with atypical benign familial neonatal epilepsy (BFNE), and to summarize the genetic characteristics of children with epilepsy caused by KCNQ gene mutation in China.

Methods

A case of BFNE who was diagnosed in West China Second University Hospital, Sichuan University in February 2021 was selected into this study for retrospective analysis of its clinical manifestations, lineage identifieation, genetic testing results and other clinical data. Taking " KCNQ gene" " epilepsy" " seizures" " epilepsy" " convulsion" as Chinese and English keywords, search CNKI, Wanfang Data Knowledge Service Platform (from database construction to nowadays), as well as Google Scholar and Pubmed database (from January 2000 to December 2020) to summarize genetic characteristics of KCNQ gene mutation-positive epilepsy patients in China. The procedure followed in this study met requirements of the Helsinki Declaration of the World Medical Association revised in 2013.

Results

① Clinical characteristics of this girl were as follows. This case was a 3-month-old girl who was admitted to hospital due to " recurrent convulsions for 1 d" . Skull MRI results showed no abnormalities. Electroencephalogram results suggested multifocal epileptic wave release. Eight people from 3 generations of this lineage were investigated. In this case, the proband, his father and grandfather had convulsions in infancy, and the BFNE of his father and grandfather disappeared at 1 year old. This child was treated with levetiracetam for 9 months and followed up to 1 year and 1 month. The child did not have convulsions until now. ②Genetic test results showed that c. 373dupG (p.A125fs) heterozygous mutation was found in the second exon of KCNQ 2 gene in this case, which was associated with benign convulsion of neonates. c. 373dupG(p.A125fs) heterozygous variation was also found in the second exon of KCNQ 2 gene in this case′s father and grandfather. ③Results of literature review were as follows. A total of 129 domestic literatures about epilepsy caused by KCNQ gene mutation were reviewed. A total of 130 Chinese cases were enrolled, including this case. Among these 130 cases, the age of onset ranged from 0 to 28 days in 72 cases, from 29 days to 2 years in 56 cases, and older than 2 year-old in 2 cases. There were 119 cases of KCNQ 2 gene variants, 11 cases of KCNQ 3 gene variants. Among 51 cases with mental/developmental disorders, 50 cases with KCNQ 2 gene mutation and 1 patient with KCNQ 3 gene mutation. And 5 dead cases were all KCNQ 2 gene mutations. Besides, the effective rate of drug use in children with epilepsy caused by KCNQ gene mutation was 69.4%(75/108), and the mortality was 4.8%(5/105).

Conclusions

KCNQ 2 gene c. 373dupG (p.A125fs) mutation may be the genetic cause of BFNE in this lineage. Epilepsy caused by KCNQ gene mutation patients in China were mainly KCNQ 2 gene mutation, and the onset age was mainly within 2 years old. And the prognosis of KCNQ 2 gene mutation was worse than that of KCNQ 3 mutation.

图1 本例患儿(先证者)(女性,3个月龄)BFNE发病家系图注:BFNE为良性家族性新生儿癫痫。Ⅰ、Ⅱ、Ⅲ分别指家系第1~3代(祖、父、孙3代)。□与○为男、女性未患病者,■与●为男、女性患病者,为先证者
图2 本例BFNE患儿(女性,3个月龄)及其父亲(23岁)、祖父(47岁)KCNQ 2基因Sanger测序峰图[图2A~2C:本例患儿及其父亲、祖父的KCNQ 2基因2号外显子存在c.373dupG(p.A125fs)杂合突变]注:BFNE为良性家族性新生儿癫痫
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