Investigators at the Institute of Neurology, London, and at other centers in the UK and the Netherlands conducted a prospective follow-up of 181 infants from the onset of febrile seizures for a median of 21.6 years, to estimate the long-term risk of developing epilepsy. Of these, 175 (97%) were seizure-free in the preceding 5 years, and 171 (94%) were seizure-free and off antiepileptic drugs. Six percent developed epilepsy. In total, 17 (7.7%) had afebrile seizures, of whom 14 (6.4%) had 2 or more afebrile seizures (epilepsy). The mean time to the second afebrile seizure was 5.7 years. At 20 years after the index febrile seizure, 6.7% had developed epilepsy. The risk of developing epilepsy in the cohort over the whole follow-up period was 10 times that of the general population. The standardized incidence ratio was significantly elevated in the 0- to 14-year age groups but not in the 15- to 19-year age group. The risk of developing epilepsy in people who had febrile seizures appears to decrease with time. A history of 4 or more febrile seizures is a risk factor for development of epilepsy. 
COMMENT. In this study, no differentiation was made between simple and complex febrile seizures. The association between febrile seizures and later epilepsy is linked to 3 possibilities: 1) febrile seizures are the first manifestation of epilepsy; 2) they are an age-specific marker of inherent susceptibility to seizures, and 3) prolonged febrile seizures (complex FS) may damage the brain with consequent increased risk of seizures . In the Collaborative Perinatal Project, 1% of children with simple febrile seizures had developed epilepsy by age 7 years. In children with complex febrile seizures, the risk was 9.2%, and in the total cohort, the risk was 2%. In children with no febrile seizures, the risk is 0.5%. The risk of epilepsy at 7 years of age in children with simple febrile seizures is two times higher, and in those with complex febrile seizures it is 18 times higher than in children with no febrile seizures. 
Febrile seizure inheritance and SUD in toddlers. SUD in 6 toddlers reported from Children’s Hospital, Boston was associated with an autosomal dominant inheritance of febrile seizures, and with hippocampal abnormalities in one of 3 autopsied cases. The autosomal dominant pattern of inheritance for febrile seizures in affected families was identical to that observed in genetic epilepsy with febrile seizures plus and familial febrile seizures. Febrile seizure may be a marker of a process that leads to SUD, and seizure may or may not be directly involved. Genetic markers are needed to identify febrile seizure patients at risk of SUD.