Childhood seizures associated with febrile episodes are relatively common and represent the majority of childhood seizures. A febrile convulsion is defined as a seizure event in infancy or childhood, usually occurring between 6 months and 6 years of ... Childhood seizures associated with febrile episodes are relatively common and represent the majority of childhood seizures. A febrile convulsion is defined as a seizure event in infancy or childhood, usually occurring between 6 months and 6 years of age, associated with fever but without any evidence of intracranial infection or defined pathologic or traumatic cause (Nabbout et al., 2002). Although the majority of patients do not develop epilepsy, the risk of developing subsequent afebrile seizures is 5 to 7 times higher in those with a history of febrile seizures compared to the general population (Annegers et al., 1987; Hedera et al., 2006). The FEB1 locus maps to chromosome 8q13-q21. - Genetic Heterogeneity of Familial Febrile Seizures FEB3A (604403) is caused by mutation in the SCN1A gene (182389) on chromosome 2q24; FEB3B (see 604403) is caused by mutation in the SCN9A gene (603415) on chromosome 2q24; FEB4 (604352) is caused by mutation in the GPR98 gene (602851) on chromosome 5q14; FEB8 (611277) is caused by mutation in the GABRG2 gene (137164) on chromosome 5q31; and FEB11 (614418) is caused by mutation in the CPA6 gene (609562) on chromosome 8q13. Several loci for familial febrile seizures have been identified: see FEB2 (602477) on chromosome 19p, FEB5 (609255) on chromosome 6q, FEB6 (609253) on chromosome 18p, FEB7 (611515) on chromosome 21q22, FEB9 (611634) on chromosome 3p24.2-p23, and FEB10 (612637) on chromosome 3q26. A phenotype termed 'generalized epilepsy with febrile seizures plus' (GEFS+; 604233) is a clinical subset of familial febrile convulsions in which affected individuals later develop afebrile seizures. GEFS+ is associated with mutations in several genes. 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.
Dibbens et al. (2010) identified a variant in the HCN2 gene (602781) that resulted in a 9-bp deletion (2156delCGCCGCCGC) removing 3 proline residues at 719 to 721 (delPPP) from a 7-proline repeat ... - Associations Pending Confirmation Dibbens et al. (2010) identified a variant in the HCN2 gene (602781) that resulted in a 9-bp deletion (2156delCGCCGCCGC) removing 3 proline residues at 719 to 721 (delPPP) from a 7-proline repeat close to the cyclic nucleotide-binding domain. The deletion was present in only 3 (0.2%) of 772 controls, but in 3 (2.5%) of 61 patients with febrile seizure and in 3 (2.3%) of 65 patients with generalized epilepsy with febrile seizures plus (GEFS+; 604233). In vitro functional expression studies in Xenopus oocytes showed that the delPPP variant had a 35% increase in current size in response to hyperpolarization compared to wildtype. This current increase would depolarize the membrane potential, taking the neuron closer to the firing potential, and thus could enhance neuronal excitability. The HCN2 delPPP variant was not observed in patients with idiopathic generalized epilepsy (EIG; 600669), who do not have febrile seizures. The findings suggested an association between variation in the HCN2 gene and predisposition to febrile seizures.
Febrile seizures occur in 2 to 5% of all children in the developed world before the age of 5 years (Wallace et al., 1996; Nabbout et al., 2002). In Japanese populations, the incidence is as high as 7% ... Febrile seizures occur in 2 to 5% of all children in the developed world before the age of 5 years (Wallace et al., 1996; Nabbout et al., 2002). In Japanese populations, the incidence is as high as 7% (Bird, 1987). In certain Pacific populations, the incidence is said to be as high as 15%. Approximately 33% of patients who experience a febrile convulsion will have a second one, and 50% of those will have a third. Two to 7% of children who experience febrile convulsions go on to develop afebrile seizure disorders and epilepsy later in life (Johnson et al., 1998).