Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.

SUMMARYUnverricht-Lundborg disease (ULD), progressive myoclonic epilepsy type 1 (EPM1, OMIM254800), is an autosomal recessively inherited neurodegenerative disorder characterized by age of onset from 6 to 16 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset ataxia, incoordination, intentional tremor, and dysarthria develop.

Summary:Purpose: To determine the point prevalence of active childhood epilepsy in a defined area and evaluate the usefulness of ILAE classification of seizures, and epilepsies/ syndromes with special interest in severe epilepsies.Methods: By using the latest ILAE International Classification of Epileptic Seizures (ICES, 1981) and Epilepsies and Epileptic Syndromes (ICE, 1989), we determined the age-and sex-specific prevalence rates of epilepsy, type of seizures, epilepsies, and recognizable epileptic syndromes, as well as the proportion of severe cases in each seizure/epilepsy/syndrome category in all children 0-15 years of age from a geographically defined area in Finland. All medical records, neurophysiological recordings and available clinical data were reviewed retrospectively.Results: Point prevalence of active epilepsy on December 12, 1992 was 3.94 per 1,000. According to ICESDCE, we were able to classify 96% of seizures and 90% of epilepsies and syndromes. Generalized seizure and epilepsy/syndrome types were more prevalent in children 0-6 years of age and partial/ localization-related in children 6-1 5 years of age. Epilepsy was intractable in 17% of all cases and correlated significantly with symptomatic etiology and early onset of epilepsy, as well as with additional neuroimpairments.Conclusions: A considerable number of cases fell into the nonspecific categories of ICE, which limits the value of present epilepsy/syndrome classification in terms of prognosis, prediction, and indication for special investigations in individual cases. A number of intractable cases was relatively low, indicating good prognosis in many childhood epilepsies, especially when additional neuroimpairments are absent.

Summary:Purpose: This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care.Methods: We reviewed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetric, demographic, and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls. The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records. The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol.Results: During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patients. We found no significant differences between WWAE and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for-gestationalage infants was significantly higher, and the head circumference was significantly smaller in WWAE. Apgar score at 1 min was lower in children of WWAE, and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls. The frequency of major malformations was 4.8% (−0.6-10.2%; 95% confidence interval) in the 127 children of WWAE.Conclusions: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care. Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed.