title: Clinical genetic study of the epilepsy-aphasia spectrum.
abstract: OBJECTIVE
  To characterize the frequency and nature of the family history of seizures in probands with epilepsy falling within the epilepsy-aphasia spectrum (EAS) in order to understand the genetic architecture of this group of disorders.
  
  
  METHODS
  Patients with epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), Landau-Kleffner syndrome (LKS), atypical benign partial epilepsy (ABPE), and intermediate epilepsy-aphasia disorders (IEAD) were recruited. All affected and available unaffected relatives up to three degrees of relatedness underwent phenotyping using a validated seizure questionnaire. Pedigrees were constructed for all families. The proportion of affected relatives according to each degree of relatedness was calculated. The epilepsy phenotypes in close relatives were analyzed. The data were compared to the families of probands with benign childhood epilepsy with centrotemporal spikes (BECTS) using the same methodology.
  
  
  RESULTS
  Thirty-one probands, including five ECSWS, three LKS, one ABPE, and 22 IEAD were recruited. The mean age of seizure onset was 3.9 (range 0.5-7) years. A male predominance was seen (68%, 21/31) . Sixteen (51.6%) of 31 had a positive family history of seizures. Among 1,254 relatives, 30 (2.4%) had a history of seizures: 13 (10.2%) of 128 first-degree relatives, 5 (1.7%) of 291 second-degree relatives, and 12 (1.4%) of 835 third-degree relatives. Thirteen had febrile seizures, including two who had both febrile seizures and epilepsy. Of the 19 relatives with epilepsy, 4 had BECTS, 4 epilepsies with focal seizures of unknown cause, 3 IEAD, and 7 unclassified. One had genetic generalized epilepsy. In the families of the BECTS probands, 9.8% of first-degree, 3% of second-degree, and 1.5% of third-degree relatives had seizures, which was not significantly different from the EAS cohort families.
  
  
  CONCLUSIONS
  The frequencies of seizures in relatives of probands with EAS suggest that the underlying genetic influence of EAS is consistent with complex inheritance and similar to BECTS. The phenotypic pattern observed in the affected relatives comprised predominantly febrile seizures and focal seizures. These findings suggest that a shared genetic predisposition to focal epilepsies underpins the epilepsy-aphasia spectrum.
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Meng-Han
authors.initials: MH
authors.lastname: Tsai
authors.forename: Danya F
authors.initials: DF
authors.lastname: Vears
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Lynette G
authors.initials: LG
authors.lastname: Sadleir
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001037:Aphasia / Q000235:genetics*; D001315:Australia; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000235:genetics / Q000523:psychology; D003627:Data Interpretation, Statistical; D004828:Epilepsies, Partial / Q000235:genetics / Q000523:psychology; D004827:Epilepsy / Q000235:genetics* / Q000523:psychology; D019305:Epilepsy, Rolandic / Q000235:genetics / Q000523:psychology; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D018887:Landau-Kleffner Syndrome / Q000235:genetics / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D010375:Pedigree; D003294:Seizures, Febrile / Q000150:complications; D055815:Young Adult