J Korean Med Sci.  2010 Feb;25(2):324-326. 10.3346/jkms.2010.25.2.324.

The First Korean Case of KCNQ2 Mutation in a Family with Benign Familial Neonatal Convulsions

• Yum MS
• Ko TS
• Yoo HW

• KMID: 1779270
• DOI: http://doi.org/10.3346/jkms.2010.25.2.324

Abstract

Neonatal seizures represent a heterogeneous group of disorders with vastly different etiologies and outcomes. Benign familial neonatal convulsions (BFNC) are a distinctive epileptic syndrome of autosomal dominant inheritance with a favorable prognosis, characterized by the occurrence of unprovoked partial or generalized clonic seizures in the neonatal period or early infancy. Recently, mutations in two potassium channel genes, KCNQ2 and KCNQ3, have been described in this disorder. In this report, we describe a family with BFNC due to a KCNQ2 mutation, the first such family to be described in the Korean population. The diagnosis of BFNC can be made based on clinical suspicion and careful history taking with special emphasis on the familial nature of the disorder. KCNQ2 mutations may be associated with BFNC in a number of different races, as has been reported in other ethnic groups.

Keyword

Epilepsy, Benign Neonatal; KCNQ2 Potassium Channel; Epilepsy; Mutation

MeSH Terms

Electroencephalography
Epilepsy, Benign Neonatal/*diagnosis/genetics
Female
Humans
Infant, Newborn
KCNQ2 Potassium Channel/*genetics
Magnetic Resonance Imaging
Mutation
Pedigree
Republic of Korea
Sequence Analysis, DNA

Figure

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  Fig. 1 The pedigree of the patients. Open symbols indicate healthy individuals and solid black symbols indicate affected individuals. An arrow indicates the index case.

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  Fig. 2 DNA analysis of the involved patients. To search for mutations in KCNQ2 in the pedigree, 16 exons and adjacent short intronic sequences of the gene were amplified by polymerase chain reaction with DNA obtained from the affected individuals. Genetic study revealed a c.1342C>T (p. Arg448X) mutation located in the C-terminal segment of KCNQ2 in the family members with neonatal seizures (Ia, IIe, IIId).

Reference

1. Ronen GM, Rosales TO, Connolly M, Anderson VE, Leppert M. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology. 1993. 43:1355–1360.

2. Plouin P, Anderson V. Roger J, Bureau M, Dravet C, Genton PT, C.A. , Wolf P, editors. Benign familial and Non-familial neonatal seizures. Epilepic syndromes in Infancy, Childhood and Adolescence. 2005. 4th ed. Montrouge, France: John Libbey Eurotext;3–15.

3. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998. 282:1890–1893.

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

5. Zonana J, Silvey K, Strimling B. Familial neonatal and infantile seizures: an autosomal-dominant disorder. Am J Med Genet. 1984. 18:455–459.

6. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson VE, Sanguinetti MC, Leppert MF. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain. 2003. 126:2726–2737.

7. Kanaumi T, Takashima S, Iwasaki H, Itoh M, Mitsudome A, Hirose S. Developmental changes in KCNQ2 and KCNQ3 expression in human brain: possible contribution to the age-dependent etiology of benign familial neonatal convulsions. Brain Dev. 2008. 30:362–369.

8. Ryan SG, Wiznitzer M, Hollman C, Torres MC, Szekeresova M, Schneider S. Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. Ann Neurol. 1991. 29:469–473.

9. Maihara T, Tsuji M, Higuchi Y, Hattori H. Benign familial neonatal convulsions followed by benign epilepsy with centrotemporal spikes in two siblings. Epilepsia. 1999. 40:110–113.

10. Coppola G, Castaldo P, Miraglia del, Bellini G, Galasso F, Soldovieri MV, Anzalone L, Sferro C, Annunziato L, Pascotto A, Taglialatela M. A novel KCNQ2 K+ channel mutation in benign neonatal convulsions and centrotemporal spikes. Neurology. 2003. 61:131–134.