Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986).
See also benign familial infantile seizures (BFIS1; ... Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). See also benign familial infantile seizures (BFIS1; 601764), which has a slightly later onset, and benign neonatal seizures (see BFNS1; 121200), which has a slightly earlier onset. See also early infantile epileptic encephalopathy-11 (613721), a more severe disorder that also results from mutations in the SCN2A gene.
Kaplan and Lacey (1983) reported a family in which 12 members had idiopathic neonatal or early infantile seizures inherited in an autosomal dominant pattern. Affected individuals had normal psychomotor development and did not develop subsequent seizures. At age ... Kaplan and Lacey (1983) reported a family in which 12 members had idiopathic neonatal or early infantile seizures inherited in an autosomal dominant pattern. Affected individuals had normal psychomotor development and did not develop subsequent seizures. At age 3.5 days, the proband developed seizures consisting of eye-blinking and lip-smacking or rhythmic twitching of the left arm and leg with the head turned to the right. A few subsequent seizures occurred, but all ceased after 6 months of age. Age at onset in other affected family members ranged from 2 days to 3.5 months, but ceased in all patients by age 7 months. Seizures occurred in clusters, usually 5 to 15, over a period of hours to a couple of days after onset. None of the patients developed a subsequent seizure disorder, and all had normal intellectual and motor development. The authors suggested the term 'benign familial neonatal-infantile seizures' to describe the disorder. Shevell et al. (1986) described 2 families demonstrating autosomal dominant inheritance of benign familial neonatal seizures (BFNC; see 121200) over 3 generations. None of the patients had seizures after the first 10 months of life, with long-term follow-up ranging from 10 months to 56 years. Development was normal, and antiepileptic drug therapy did not appear to modify either seizure recurrence or long-term outcome. Lewis et al. (1996) studied one of the pedigrees described by Shevell et al. (1986), with the inclusion of additional individuals. Several individuals had onset at 3 to 3.5 months, later than that typical for BFNC, which has onset within the first week of life. Noting that the age at onset in benign familial infantile convulsions (BFIC; see 601764) is typically between 4 and 8 months, the authors concluded that the age at onset in this family was intermediate between that seen in BFNC and BFIC. Lewis et al. (1996) termed BFNC and BFIC 'benign familial convulsions of early life.' Berkovic et al. (2004) reported 5 families with benign familial neonatal-infantile seizures. Age at onset ranged from 2 days to 7 months (mean 11.2 weeks). Seizures were predominantly afebrile partial seizures with secondary generalization. Focal motor manifestations were usually noted first, typically head and eye deviation, although apnea and staring also occurred. All patients stopped having seizures by age 12 months with no subsequent neurologic deficits. - Clinical Variability Sugawara et al. (2001) reported a 6-year-old Japanese boy with normal development who had onset of febrile seizures at age 8 months, and later had 5 episodes of brief afebrile atonic seizures lasting less than 10 seconds since age 4 years. EEG showed single spikes over the right frontal region. Both parents, who were not related, had a history of febrile seizures in childhood. Genetic analysis identified a heterozygous mutation in the SCN2A gene (R188W; 182390.0001) in the boy and the father, but not the mother. Although the authors suggested a link to GEFS+ (604233), they noted that assignment of the phenotype in this patient was difficult because both parents had febrile seizures, which have a high frequency in the general population. Berkovic et al. (2004) concluded that there is little support for an association between SCN2A and GEFS+, despite the report of Sugawara et al. (2001). Berkovic et al. (2004) also stated that seizures with fever occasionally do occur in BFNIS.
In the family reported by Shevell et al. (1986) and Lewis et al. (1996), and in a second family in which seizure onset occurred predominantly after 1 month of age, Heron et al. (2002) found mutations in the ... In the family reported by Shevell et al. (1986) and Lewis et al. (1996), and in a second family in which seizure onset occurred predominantly after 1 month of age, Heron et al. (2002) found mutations in the SCN2A gene in affected individuals: a leu1563-to-val (182390.0003) mutation in the family of Shevell et al. (1986), and a leu1330-to-phe (182390.0002) mutation in the second family. Both of these mutations disrupted a conserved leucine, and both were predicted to reduce the rate of inactivation of the sodium channel, leading to increased ion flow through the channel and hyperexcitability. In affected members of multiple families, including those originally reported by Kaplan and Lacey (1983) and Malacarne et al. (2001), Berkovic et al. (2004) identified mutations in the SCN2A gene (182390.0004-182390.0007).