BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a recently described benign childhood-onset epileptic syndrome with autosomal dominant inheritance. The most common phenotypes are febrile seizures (FS) often with accessory afebrile generalized tonic-clonic seizures (GTCS, FS(+)). In about one third, additional seizure types occur, such as absences, myoclonic, or atonic seizures. So far, three mutations within genes encoding subunits of neuronal voltage-gated Na(+) channels have been found in GEFS(+) families, one in SCN1B (beta(1)-subunit) and two in SCN1A (alpha-subunit). METHODS: The authors examined the phenotypic variability of GEFS(+) in a five-generation German family with 18 affected individuals. Genetic linkage analysis was performed to exclude candidate loci. RESULTS: Inheritance was autosomal dominant with a penetrance of about 80%. A variety of epilepsy phenotypes occurred predominantly during childhood. Only four individuals showed the FS or FS(+) phenotype. The others presented with different combinations of GTCS, tonic seizures, atonic seizures, and absences, only in part associated with fever. The age at onset was 2.8 +/- 1.3 years. Interictal EEG recordings showed rare, 1- to 2-second-long generalized, irregular spike-and-wave discharges of 2.5 to 5 Hz in eight cases and additional focal parietal discharges in one case. Linkage analysis excluded the previously described loci on chromosomes 2q21-33 and 19q13. All other chromosomal regions containing known genes encoding neuronal Na(+) channel subunits on chromosomes 3p21-24, 11q23, and 12q13 and described loci for febrile convulsions on chromosomes 5q14-15, 8q13-21, and 19p13.3 were also excluded. CONCLUSION: These results indicate further clinical and genetic heterogeneity in GEFS(+).
BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a recently described benign childhood-onset epileptic syndrome with autosomal dominant inheritance. The most common phenotypes are febrile seizures (FS) often with accessory afebrile generalized tonic-clonic seizures (GTCS, FS(+)). In about one third, additional seizure types occur, such as absences, myoclonic, or atonic seizures. So far, three mutations within genes encoding subunits of neuronal voltage-gated Na(+) channels have been found in GEFS(+) families, one in SCN1B (beta(1)-subunit) and two in SCN1A (alpha-subunit). METHODS: The authors examined the phenotypic variability of GEFS(+) in a five-generation German family with 18 affected individuals. Genetic linkage analysis was performed to exclude candidate loci. RESULTS: Inheritance was autosomal dominant with a penetrance of about 80%. A variety of epilepsy phenotypes occurred predominantly during childhood. Only four individuals showed the FS or FS(+) phenotype. The others presented with different combinations of GTCS, tonic seizures, atonic seizures, and absences, only in part associated with fever. The age at onset was 2.8 +/- 1.3 years. Interictal EEG recordings showed rare, 1- to 2-second-long generalized, irregular spike-and-wave discharges of 2.5 to 5 Hz in eight cases and additional focal parietal discharges in one case. Linkage analysis excluded the previously described loci on chromosomes 2q21-33 and 19q13. All other chromosomal regions containing known genes encoding neuronal Na(+) channel subunits on chromosomes 3p21-24, 11q23, and 12q13 and described loci for febrile convulsions on chromosomes 5q14-15, 8q13-21, and 19p13.3 were also excluded. CONCLUSION: These results indicate further clinical and genetic heterogeneity in GEFS(+).
Authors: Julian Schubert; Aleksandra Siekierska; Mélanie Langlois; Patrick May; Clément Huneau; Felicitas Becker; Hiltrud Muhle; Arvid Suls; Johannes R Lemke; Carolien G F de Kovel; Holger Thiele; Kathryn Konrad; Amit Kawalia; Mohammad R Toliat; Thomas Sander; Franz Rüschendorf; Almuth Caliebe; Inga Nagel; Bernard Kohl; Angela Kecskés; Maxime Jacmin; Katia Hardies; Sarah Weckhuysen; Erik Riesch; Thomas Dorn; Eva H Brilstra; Stephanie Baulac; Rikke S Møller; Helle Hjalgrim; Bobby P C Koeleman; Karin Jurkat-Rott; Frank Lehman-Horn; Jared C Roach; Gustavo Glusman; Leroy Hood; David J Galas; Benoit Martin; Peter A M de Witte; Saskia Biskup; Peter De Jonghe; Ingo Helbig; Rudi Balling; Peter Nürnberg; Alexander D Crawford; Camila V Esguerra; Yvonne G Weber; Holger Lerche Journal: Nat Genet Date: 2014-11-02 Impact factor: 38.330
Authors: Stefan Wolking; Patrick May; Davide Mei; Rikke S Møller; Simona Balestrini; Katherine L Helbig; Cecilia Desmettre Altuzarra; Nicolas Chatron; Charu Kaiwar; Katharina Stöhr; Peter Widdess-Walsh; Bryce A Mendelsohn; Adam Numis; Maria R Cilio; Wim Van Paesschen; Lene L Svendsen; Stephanie Oates; Elaine Hughes; Sushma Goyal; Kathleen Brown; Margarita Sifuentes Saenz; Thomas Dorn; Hiltrud Muhle; Alistair T Pagnamenta; Dimitris V Vavoulis; Samantha J L Knight; Jenny C Taylor; Maria Paola Canevini; Francesca Darra; Ralitza H Gavrilova; Zöe Powis; Shan Tang; Justus Marquetand; Martin Armstrong; Duncan McHale; Eric W Klee; Gerhard J Kluger; Daniel H Lowenstein; Sarah Weckhuysen; Deb K Pal; Ingo Helbig; Renzo Guerrini; Rhys H Thomas; Mark I Rees; Gaetan Lesca; Sanjay M Sisodiya; Yvonne G Weber; Dennis Lal; Carla Marini; Holger Lerche; Julian Schubert Journal: Neurology Date: 2019-02-08 Impact factor: 11.800
Authors: Giulia Spoto; Giulia Valentini; Maria Concetta Saia; Ambra Butera; Greta Amore; Vincenzo Salpietro; Antonio Gennaro Nicotera; Gabriella Di Rosa Journal: Front Neurol Date: 2022-03-08 Impact factor: 4.003