Benign familial neonatal seizures is an autosomal dominant disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age. The disorder is distinguished from benign familial ... Benign familial neonatal seizures is an autosomal dominant disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age. The disorder is distinguished from benign familial infantile seizures (BFIS1; 601764) by an earlier age at onset. Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm. - Genetic Heterogeneity of Benign Familial Neonatal Seizures See also BFNS2 (121201), which is caused by mutation in the KCNQ3 gene (602232) on chromosome 8q24, and BFNS3 (608217), which has been associated with a pericentric inversion on chromosome 5. See 269720 for a possible autosomal recessive form.
Rett and Teubel (1964) and Bjerre and Corelius (1968) reported families in which multiple persons had neonatal convulsions that cleared spontaneously after a few weeks and were followed by normal psychomotor development. Inheritance was autosomal dominant. Pyridoxine dependency ... Rett and Teubel (1964) and Bjerre and Corelius (1968) reported families in which multiple persons had neonatal convulsions that cleared spontaneously after a few weeks and were followed by normal psychomotor development. Inheritance was autosomal dominant. Pyridoxine dependency was excluded in all. Zimprich et al. (2006) provided follow-up of the original family reported by Rett and Teubel (1964). There were 9 affected individuals spanning 4 generations. The 2 index patients had their first seizures on the third day of life. Seizures recurred 15 to 20 times daily for the first few weeks and then remitted. Seizures started uniformly with brief generalized tonic posturing and cyanosis followed by a generalized clonic phase including facial and ocular manifestations. Unilateral or focal features were not observed, and 9 of 10 seizures occurred during sleep. Later in childhood, 3 of the 9 affected individuals developed nocturnal generalized tonic-clonic seizures; 2 of the 3 also had simple focal orofacial seizures. In the case reported by Carton (1978), strong paroxysmal fetal movements were perceived during the last 2 months of pregnancy, possibly indicating intrauterine convulsions. Herranz and Arce (1979) reported 13 affected persons in 5 generations of a family. No convulsions occurred after the 40th day of life, and development in all but one was normal. Pettit and Fenichel (1980) reported a family with 5 affected members. One patient died during a cyanotic spell, and the remainder were developmentally and neurologically normal, although 3 continued to have seizure disorders as adults. Tibbles (1980) described 3 families with benign neonatal seizures with male-to-male transmission in 2 of them. Tibbles (1980) suggested that persons with this disorder have an increased risk of the later development of epilepsy. Dobrescu and Larbrisseau (1982) described a family with 12 affected members in 3 generations. Zonana et al. (1984) reported a family with 6 affected individuals in 3 generations. Analysis of the clinical features of their family and of 15 previously reported families (116 patients total) revealed a typical clinical phenotype with onset of seizures by 2 to 8 days of life and cessation of seizures by 1 to 6 months. Long-term neurodevelopmental outcome was normal, except for an increased rate (11%) of subsequent seizures in childhood or adulthood. Cunniff et al. (1988) described a family with 8 affected persons in 2 generations. Ryan et al. (1991) reported an affected family with a variable phenotype: seizures frequently did not remit until 6 to 24 months; febrile convulsions occurred in at least 2 patients; apparent audiogenic seizures occurred in 4 patients; and 1 individual had refractory epilepsy until late adolescence. The family showed linkage to chromosome 20q. On the basis of a kindred with 69 affected individuals, Ronen et al. (1993) defined the seizure characteristics in chromosome 20-linked BFNC. Seizure onset occurred on day 3 in 42%, and remission took place in 68% during the first 6 weeks. Seizures were brief and of a mixed type, starting with tonic posture, ocular symptoms, apnea, and other autonomic features. The seizure often progressed to clonic movements and motor automatisms. The postictal state was brief, and interictally the neonates looked well. The ictal EEG pattern showed with generalized suppression of amplitude on onset. Neurocognitive outcome was usually normal, but the risk for subsequent epilepsy was 16%. Most of the later epilepsy was generalized tonic or tonic-clonic, and some seizures were provoked, raising the possibility of an unusual form of reflex epilepsy. In a large family in which 13 individuals had benign neonatal convulsions, Berkovic et al. (1994) found that 10 patients had neonatal seizures and 4 had febrile seizures, including 2 without neonatal convulsions. Two individuals had afebrile seizures later, 1 of whom had not previously demonstrated neonatal or febrile seizures. Three obligate carriers had no known seizures. The authors emphasized the phenotypic heterogeneity. - Benign Familial Neonatal Seizures 1 and/or Myokymia Dedek et al. (2001) reported a German family in which twin sisters had BFNS. Both later had grand mal seizures at ages 2 and 12 to 13 years, some of which were associated with fever. Both complained about exercise-induced myalgia in preschool, but this resolved by adolescence. Both girls also developed myokymia later in childhood, characterized by involuntary movements of the limbs, fingers, and toes, and spontaneous repetitive discharges on EMG. Both had mild learning disabilities. A half-sister had recurrent neonatal convulsions with tonic and/or clonic limb movements in infancy. Myokymia became apparent at age 3 years. A son of 1 of the twins had neonatal convulsions without neurologic abnormalities or myokymia at age 1 year. However, EMG showed spontaneous discharges of grouped motor unit potentials, consistent with myokymic discharges. Inheritance was autosomal dominant. Wuttke et al. (2007) reported a 25-year-old Egyptian man with isolated myokymia and no history of neonatal seizures. There was no family history of epilepsy or peripheral nerve hyperexcitability. Clinically, the patient had had permanent muscle overactivity in the distal upper extremities and small amplitude movements of the fingers, which were not disabling. However, he also reported exercise-induced cramps of both hands since childhood and 4 episodes of exercise-induced generalized muscle stiffness. EMG showed spontaneous irregular discharges consistent with myokymia. He showed a favorable response to treatment with retigabine.
In affected members of the family reported by Berkovic et al. (1994), Biervert et al. (1998) identified a heterozygous truncating mutation in the KCNQ2 gene (602235.0003). One mutation carrier was unaffected, consistent with reduced penetrance.
In ... In affected members of the family reported by Berkovic et al. (1994), Biervert et al. (1998) identified a heterozygous truncating mutation in the KCNQ2 gene (602235.0003). One mutation carrier was unaffected, consistent with reduced penetrance. In affected members from 6 families with BFNS, Singh et al. (1998) identified 6 different mutations in the KCNQ2 gene (see, e.g., 602235.0001-602235.0002). In affected members of a German family with familial neonatal convulsions followed by myokymia, Dedek et al. (2001) identified a heterozygous mutation in the KCNQ2 gene (R207W; 602235.0006). One of the patients had isolated myokymia without seizures. Dedek et al. (2001) noted that 1 of the main pathophysiologic mechanisms of peripheral nerve hyperexcitability in myokymia is suppression of outward potassium currents (Lee et al., 1998). In a patient with isolated myokymia, Wuttke et al. (2007) identified a heterozygous mutation in the KCNQ2 gene (R207Q; 602235.0011). In affected members of the original BFNS1 family reported by Rett and Teubel (1964), Zimprich et al. (2006) identified a heterozygous mutation in the KCNQ2 gene (602235.0010). Heron et al. (2007) identified 3 deletions and 1 duplication of more than 1 exon of the KCNQ2 gene in 4 (44%) of 9 unrelated families with benign familial neonatal seizures who had previously tested negative for coding or splice site mutations. The changes were predicted to result in haploinsufficiency. The authors suggested that multiplex ligation-dependent probe amplification (MLPA) should be a second-tier testing strategy in candidate cases.