Skip to main content
SpringerLink
Log in

Infantile seizures and other epileptic phenotypes in a Chinese family with a missense mutation of KCNQ2

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Introduction

Benign familial infantile seizures (BFIS) is a form of idiopathic epilepsy characterized by clusters of afebrile seizures occurring around the sixth month of life and a favorable outcome. Linkage analysis has revealed that three chromosomal segments, 19q12-q13.1, 16p12-q12, and 2q23-31, are linked to this disorder.

Subjects and methods

We report here a large Chinese family in which all 17 affected members had had infantile seizures with onset at age 2–4 months, with two of these also manifesting seizures later in life accompanied with either choreoathetosis or myokymia. Linkage analysis in this family confirmed a previous report of genetic heterogeneity in BFIS – since linkage was excluded at the above-mentioned known BFIS loci – and suggested a possible linkage to the KCNQ2 gene, which is believed to be a voltage gated potassium channel gene responsible for benign familial neonatal seizures (BFNS).

Results and discussion

Sequencing of the KCNQ2 gene revealed that all 17 affected family members carried a heterozygous Gly-to-Val (G271V) mutation in the conserved pore region that resulted from a guanine-to-thymine transition in exon 5 of KCNQ2. The same mutation with a comparable localization in the KCNQ3 (G310V) gene has been found in BFNS patients. The same conserved amino acid was also found to be mutated in the KCNQ1 gene in a family with Long QT Syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

BFIS:

Benign familial infantile seizures

BFNS:

Benign familial neonatal seizures

EEG:

Electroencephalograms

KCNQ:

Potassium channel subfamily Q member

LQTS:

Long QT syndrome

References

  1. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK (1998) A potassium channel mutation in neonatal human epilepsy. Science 279:403–406

    Article  PubMed  CAS  Google Scholar 

  2. Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, Soldovier MV, Baschirotto C, Bresolin N, Dalla Bernardina B, Taglialatela M, Bassi MT (2004) A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 63:57–65

    PubMed  CAS  Google Scholar 

  3. Caraballo R, Pavek S, Lemainque A, Gastaldi M, Echenne B, Motte J, Genton P, Cersosimo R, Humbertclaude V, Fejerman N, Monaco AP, Lathrop MG, Rochette J, Szepetowski P (2001) Linkage of benign familial infantile convulsions to chromosome 16p12-q12 suggests allelism to the infantile convulsions and chroeatherosis syndrome. Am J Hun Genet 68:788–794

    Article  CAS  Google Scholar 

  4. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, Leppert M (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 18:53–55

    Article  PubMed  CAS  Google Scholar 

  5. Dedek K, Fusco L, Teloy N, Steinlein OK (2003) Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2. Epilepsy Res 54:21–27

    Article  PubMed  CAS  Google Scholar 

  6. Engel J Jr (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on classification and terminology. Epilesia 42:796–803

    Article  Google Scholar 

  7. Guipponi M, Rivier F, Vigevano F, Beck C, Crespel A, Echenne B, Lucchini P, Sebastianelli R, Baldy-Moulinier M, Malafosses A (1997) Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q. Hum Mol Genet 6:472–477

    Article  Google Scholar 

  8. Heron SE, Crossl KM, Andermann E, Phillips HA, Hall AJ, Bleasel A, Shevell M, Mercho S, Seni MH, Guiot MC, Mulley JC, Berkovic SF, Scheffer IE (2002) Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 360:851–852

    Article  PubMed  CAS  Google Scholar 

  9. Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T, Yonetani M, Tsutsumi M, Muranaka H, Kurokawa T, Hanai T, Wada K, Kaneko S, Mitsudome A (2000) A novel mutation of KCNQ3 (c.925T->C) in a Japanese family with benign familial neonatal convulsions. Ann Neurol 47:822–826

    Article  PubMed  CAS  Google Scholar 

  10. Lee WL, Low PS, Rajan U (1993) Benign familial infantile epilepsy. J Pediatr 123:588–590

    Article  PubMed  CAS  Google Scholar 

  11. Malacarrne M, Gennaro E, Madia F, Pozzi S, Vacaa D, Barone B, dalla Bernardina B, Bianchi A, Bonanni P, De Marco P, Gambardella A, Giordano L, Lispi ML, Romeo A, Santorum E, Vanadia F, Vecchi M, Veggiotti P, Vigevano F, Viri F, Bricarelli FD, Zara F (2001) Benign familial infantile convulsions: mapping of a novel locus on chromosome 2q24 and evidence for genetic heterogeneity. Am J Hum Genet 68:1521–1526

    Article  Google Scholar 

  12. Malafosse A, Beck C, Bellet H, Di Capua M, Dulac O, Echenne B, Fusco L, Vigevano F (1994) Benign infantile familial convulsions are not an allelic form of the benign familial neonatal convulsions gene. Ann Neurol 35:480–482

    Article  Google Scholar 

  13. Pasquale S, Laura B, Maria Luisa L, Nicola S, Carlo M, Federico V, Federico Z (2006) A novel SCN2A mutation in family with benign familial infantile seizures. Epilepsia 47:218–220

    Article  Google Scholar 

  14. Pereira S, Roll P, Krizova J, Genton P, Brazdil M, Kuba R, Cau P, Rektor I, Szeptowski P (2004) Complete loss of the cytoplasmic carboxyl terminus of the KCNQ2 potassium channel: a novel mutation in a large Czech pedigree with benign neonatal convulsions or other epileptic phenotypes. Epilepsia 45:384–390

    Article  PubMed  CAS  Google Scholar 

  15. Schmitt B, Woglrab G, Sander T, Steinlein OK, Hajnal BL (2005) Neonatal seizures with tonic clonic sequences and poor developmental outcome. Epilepsy Res 65:161–168

    Article  PubMed  Google Scholar 

  16. Schroeder BC, Kubisch C, Stein V, Jentsch TJ (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 396:687–690

    Article  PubMed  CAS  Google Scholar 

  17. Seebohm G, Pusch M, Chen J, Sanguinetti M (2003) Pharmacological Activation of normal and arrhythmia-associated mutant KCNQ1 potassium. Circ Res 93:941–947

    Article  PubMed  CAS  Google Scholar 

  18. Wang JQ, Li HM, Yin JG, Zhang HY, Li C, Gu RJ, Jia FJ, Huo WH, Guo XP (2002) Linkage mapping of benign familial infantile convulsions(BFIC) and sequencing analysis of KCNQ2 gene in a BFIC family. Zhonghua Er Ke Za Zhi 40:513–517

    Google Scholar 

  19. Wideckenden AD, Yu W, Zou A, Jegla T, Wagoner PK (2000) Retigabine, a novel anticonvulsant, enhances activation of KCNQ2/3 potassium channels. Mol Pharmacol 58:591–600

    Google Scholar 

  20. Xiao B, Deng FY, Xiong G, Wang K, Zhang J, Chen XD, Liu YZ, Deng HW (2005) Clinical and genetic study on a new Chinese family with benign familial infantile seizures. Eur J Neurol 12:344–349

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank all of the family members who participated in this study, and Dingbian Country Hospital of Shaanxi Province and the physicians who facilitated contact with the family members. Each participant gave informed consent before the study. The experiments performed in this paper comply with the current laws of the China. This research was supported by grants 30571597 from the National Nature Science Foundation.

Author information

Authors and Affiliations

  1. Department of Cardiology, First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases (Xi’an Jiaotong University), Ministry of Education, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Aiqun Ma

  2. Department of Pediatrics, First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases (Xi’an Jiaotong University), Ministry of Education, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Xihui Zhou, Xiaohong Liu, Yanmin Zhang, Ruiming Shi & Tao Geng

  3. Central laboratory of Biochemical Research, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Chen Huang

  4. Department of Forensic Medicine, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Shiwei Mao & Shengbin Li

Authors
  1. Xihui Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiqun Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chen Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanmin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruiming Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiwei Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tao Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shengbin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aiqun Ma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, X., Ma, A., Liu, X. et al. Infantile seizures and other epileptic phenotypes in a Chinese family with a missense mutation of KCNQ2. Eur J Pediatr 165, 691–695 (2006). https://doi.org/10.1007/s00431-006-0157-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-006-0157-5

Keywords

Search

Navigation