Benign familial infantile seizure is an autosomal dominant disorder characterized by afebrile partial complex or generalized tonic-clonic seizures occurring between 3 and 12 months of age with a good response to medication and no neurologic sequelae. Seizures usually ... Benign familial infantile seizure is an autosomal dominant disorder characterized by afebrile partial complex or generalized tonic-clonic seizures occurring between 3 and 12 months of age with a good response to medication and no neurologic sequelae. Seizures usually remit by age 18 months (summary by Weber et al., 2004). For a phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). Benign familial infantile seizures can also occur in 2 allelic disorders: infantile convulsions and choreoathetosis (ICCA; 602066) and paroxysmal kinesigenic choreoathetosis (EKD1; 128200).
Caraballo et al. (2001) identified and studied 7 families with autosomal dominant BFIS. In 1 family, Caraballo et al. (2001) observed a patient who was clearly homozygous for the BFIS2 gene. Infantile convulsions did not respond well to ... Caraballo et al. (2001) identified and studied 7 families with autosomal dominant BFIS. In 1 family, Caraballo et al. (2001) observed a patient who was clearly homozygous for the BFIS2 gene. Infantile convulsions did not respond well to anticonvulsants, in contrast to all other affected members of his family and to classic BFIS. In addition, although the families had been selected on the basis of clinical evidence of BFIS only, this patient had atypical paroxysmal choreic/dystonic dyskinesia beginning at age 2 years. The age of onset was earlier than that of classic paroxysmal dyskinesias (which usually begins at age 5 to 16 years). Dyskinetic movements sometimes occurred a few seconds after starting exertion, which suggested a kinesigenic type. However, the patient did not respond to carbamazepine, a finding that is consistent with an exertional rather than a kinesigenic type. Weber et al. (2004) reported 14 families with BFIS2 showing linkage to chromosome 16p12-q12. Onset of seizures occurred between 2 and 7 months of age and disappeared at the latest by age 18 months. Seizure types included complex partial seizures and generalized tonic-clonic seizures. Other features included loss of consciousness, paleness, cyanosis, hypotonia, gaze deviation, and focal clonicity. Medication was effective, and could be stopped by age 4 years without seizure relapse. Most interictal EEG did not show abnormalities, but some had focal seizure activity. Schubert et al. (2012) reported 39 families with BFIS2. The phenotype was homogeneous, with an onset of seizures between 3 and 12 months of age and a benign outcome in almost all cases without long-term anticonvulsive treatment. Seizure types mainly included complex partial seizures and generalized tonic-clonic seizures. Some patients reported migraine, but none had febrile seizures, choreoathetosis, or dyskinesia. Some of the families had previously been reported by Striano et al. (2006) and Weber et al. (2004).
In affected members of 14 (82%) of 17 families with benign familial infantile seizures-2, Heron et al. (2012) identified heterozygous mutations in the PRRT2 gene (see, e.g., 614386.0001 and 614386.0006). The 649insC mutation (614386.0001) was the most common ... In affected members of 14 (82%) of 17 families with benign familial infantile seizures-2, Heron et al. (2012) identified heterozygous mutations in the PRRT2 gene (see, e.g., 614386.0001 and 614386.0006). The 649insC mutation (614386.0001) was the most common mutation, found in 12 families with BFIS2. Heterozygous mutations in the PRRT2 gene were also found in 5 (83%) of 6 families with familial infantile convulsions with paroxysmal choreoathetosis (ICCA; 602066), a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (EKD1; 128200), cooccur. The 649insC mutation was found in 3 families with ICCA. The families with this mutation were of different ethnic origin, including Australasian of western European heritage, Swedish, and Israeli Sephardic-Jewish, and there was no evidence of a common haplotype among these families, indicating a mutation hotspot. These findings demonstrated that mutations in PRRT2 cause both epilepsy and a movement disorder, with obvious pleiotropy in age of expression. The mutations were identified by linkage analysis, confirming linkage to chromosome 16p, followed by sequence-capture array of coding and promoter sequences within the candidate region. Schubert et al. (2012) identified a heterozygous 649dupC mutation in the PRRT2 gene in 39 of 49 families with BFIS2 and in 1 patient with sporadic occurrence of the disorder (77% of index cases). Three additional heterozygous PRRT2 mutations (see, e.g., 614386.0013; 614386.0014) were found in 3 other families with the disorder. The patients were of German, Italian, Japanese, and Turkish origin. Some of the families had previously been reported by Striano et al. (2006) and Weber et al. (2004). The 649dupC mutation, which occurs in an unstable DNA sequence of 9 cytosines, arose independently in families of different origin. Some unaffected family members also carried the mutation, indicating incomplete penetrance. Ono et al. (2012) identified the 649dupC mutation in 14 of 15 Japanese families with EKD1 and in 2 Japanese families with BFIS2. The mutation was shown to occur de novo in at least 1 family, suggesting that it is a mutation hotspot. EKD1, ICCA, and BFIS2 segregated with the mutation even within the same family. The findings indicated that all 3 disorders are allelic and are likely caused by a similar mechanism. In 1 family, a Japanese mother and daughter both carried a heterozygous mutation (Q250X; 614386.0015). The mother had EKD1 and her daughter had BFIS2.