Seizures, Benign Familial Neonatal, 2

A number sign (#) is used with this entry because benign familial neonatal seizures-2 (BFNS2) is caused by heterozygous mutation in the KCNQ3 gene (602232) on chromosome 8q24.

Description

Benign familial neonatal seizures-2 is an autosomal dominant neurologic condition characterized by onset of clonic or tonic-clonic seizures in the first few days of life. Seizures tend to last for about a minute, may occur several times a day, and are responsive to medication. Almost all patients have full remission within the first months of life, although some rare patients may have a few seizures later in childhood. EEG, brain imaging, and psychomotor development are usually normal (summary by Fister et al., 2013).

For a general phenotypic description and a discussion of genetic heterogeneity of benign familial neonatal seizures, see BFNS1 (121200).

Clinical Features

Ryan et al. (1991) reported a large 3-generation family of Mexican American origin in which 14 individuals had benign neonatal epilepsy manifest as clonic seizures. All affected individuals had onset of seizures between the second and fourteenth day of life, and none had seizures after 2 months of age. EEG and brain imaging were normal, and all patients showed normal intellectual development.

Hirose et al. (2000) reported a Japanese family in which several members had onset of clonic or tonic-clonic seizures in the first week of life. Seizures disappeared by 2 weeks of life in all affected individuals except 2: these 2 patients had complex partial seizures with occasional secondary generalization at ages 6 months and 3 years, respectively. None of the patients showed intellectual delay.

Li et al. (2008) reported a 3-generation Chinese family in which 7 individuals had benign neonatal seizures. Affected individuals developed afebrile seizures between 2 and 3 days after birth, followed by remission during 1 month without recurrence. Most patients had partial clonic seizures that lasted from 30 seconds to 1 minute and occurred from 1 to 10 times a day. One patient had paroxysmal squeals. EEG and brain imaging were normal in all patients studied.

Fister et al. (2013) reported a mother and daughter of Slovenian descent with BFNS2. The patients developed focal clonic seizures on the third and fifth days of life, respectively. The seizures in the daughter lasted from thirty seconds to 2 minutes. At age 2.5 years, she was seizure-free and developing normally. The mother had recurrence of seizures at age 3 weeks, but thereafter was seizure-free and had normal development. The seizures in both patients were responsive to phenobarbital.

Inheritance

The transmission pattern of benign neonatal seizures in the families reported by Ryan et al. (1991), Hirose et al. (2000), and Li et al. (2008) was consistent with autosomal dominant inheritance.

Mapping

Using dinucleotide repeat markers distributed throughout the genome to analyze an affected family reported by Ryan et al. (1991), Lewis et al. (1993) demonstrated linkage of benign neonatal epilepsy to markers D8S284 and D8S256 on chromosome 8q (maximum pairwise lod score of 4.43). Multipoint analysis placed the BFNS2 locus in the interval spanned by D8S198-D8S274. The kindred was of Mexican American ancestry.

Molecular Genetics

In an affected member of the large BFNC family previously reported by Ryan et al. (1991) and Lewis et al. (1993), Charlier et al. (1998) identified a mutation in the KCNQ3 gene (G263V; 602232.0001) that cosegregated with the BFNC phenotype.

In affected members of a Japanese family with BFNS2, Hirose et al. (2000) identified a heterozygous missense mutation in the KCNQ3 gene (W309R; 602232.0002).

In affected members of a Chinese family with benign neonatal seizures, Li et al. (2008) identified a heterozygous mutation in the KCNQ3 gene (R330C; 602232.0003). The mutation, which was found by linkage analysis followed by candidate gene sequencing, segregated with the disorder in the family. Fister et al. (2013) identified a heterozygous R330C mutation in the KCNQ3 gene in a Slovenian mother and daughter with benign neonatal seizures-2.