Seizures, Benign Familial Infantile, 1

Description

Benign familial infantile seizures (BFIS) is a seizure disorder of early childhood with age at onset from 3 months up to 24 months. It is characterized by brief seizures beginning with slow deviation of the head and eyes to 1 side and progressing to generalized motor arrest and hypotonia, apnea and cyanosis, and limb jerks. Seizures usually occur in clusters over a day or several days. The ictal EEG shows focal parietal-temporal activity, whereas the interictal EEG is normal. Concurrent and subsequent psychomotor and neurologic development are normal (Franzoni et al., 2005).

See also benign familial neonatal seizures (BFNS1; 121200).

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 Infantile Seizures

The BFIS1 locus has been mapped to chromosome 19q. BFIS2 (605751) is caused by mutation in the PRRT2 gene on chromosome 16p11. BFIS3 (607745), which is caused by the mutations in the SCN2A gene (182390) on chromosome 2q24, has a slightly earlier age at onset and is sometimes termed benign familial 'neonatal-infantile' seizures. BFIS4 (612627) has been mapped to chromosome 1p. BFIS5 (617080) is caused by mutation in the SCN8A gene (600702) on chromosome 12q13. BFIS6 (see 610353) is caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21.

Clinical Features

Benign familial infantile convulsions was described by Vigevano et al. (1992) in 5 families of Italian ancestry. Affected children had seizure onset between 4 and 6 months; seizures occurred in clusters and showed good response to pharmacologic treatment. Seizures were partial with secondary generalization, and were characterized by head and eye deviation followed by diffuse hypertonia and bilateral limb jerks. In 4 of the families, the inheritance was clearly autosomal dominant; in 1 family, 2 affected male first cousins were the offspring of ostensibly unaffected brothers.

Lee et al. (1993) reported 23 affected infants from 11 families from Singapore. Age at onset ranged from 3 to 19 months, and patients had normal neurologic development. Echenne et al. (1994) reported 6 infants from 3 French families who experienced clusters of brief seizures with onset between 3 and 12 months of age. The patients responded well to conventional anticonvulsants which were then discontinued without recurrence of seizures or psychomotor retardation. In all 3 kindreds, there was apparent autosomal dominant transmission of the disorder, although no male-to-male transmission occurred. None of the affected members had febrile seizures. In contrast to the patients reported by Vigevano et al. (1992) who had partial seizures, the patients reported by Echenne et al. (1994) had generalized seizures of various types: clonic, tonic, or atonic.

Franzoni et al. (2005) evaluated 58 Italian patients with benign infantile convulsions: 17 (29%) had a family history of benign epilepsy, 12 (21%) had a family history of febrile convulsions, 25 (43%) had no family history, and 4 (7%) had an uncertain family history. Psychomotor development before and after the seizures was normal in all infants, and none had neurologic abnormalities. Thirteen (76%) of 17 BFIS patients had onset before 12 months of age, compared to 56% of nonfamilial patients. In all patients, seizures occurred in clusters, twice a day or more, for 1 to 4 days. During seizures, patients showed psychomotor arrest, deviation of the eyes to 1 side, hypertonia, and apnea with cyanosis. Ictal EEG patterns tended to show focal paroxysmal discharges arising in the central, parietal, or temporal regions with occasional generalization. Franzoni et al. (2005) emphasized the benign outcome of BFIS and noted that pharmacologic management may not always be necessary.

Mapping

By performing linkage analysis of 8 previously described families with benign familial infantile convulsions and markers for the chromosome 20 locus implicated in benign familial neonatal convulsions (BFNS1; 121200), Malafosse et al. (1994) determined that the EBN1 gene is not responsible for BFIS and that the 2 are not allelic disorders. In 5 of these families, Guipponi et al. (1997) mapped the BFIS gene to chromosome 19q by linkage analysis. They obtained a maximum 2-point lod score of 6.36 at D19S114 and maximum multipoint lod scores greater than 8 for the interval D19S250-D19S245. The identification of a common haplotype in these Italian 19q-linked BFIS families suggested a founder effect.

Molecular Genetics

Exclusion Studies

Moulard et al. (2000) did not identify any mutations in the SCN1B gene (600235) in 10 Caucasian BFIC probands from western Europe, Mutations in the SCN1B gene have been shown to cause generalized epilepsy with febrile seizures plus (GEFS+; 604233).