PURPOSE: The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25-70% of the patients having a family history of febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder. METHODS: We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families. Familial clustering and syndromic concordance within the affected relatives in both groups were investigated. RESULTS: The frequency of FS or epilepsy in relatives of SMEI patients did not significantly differ from that in controls (FS: 13 of 867 vs. 12 of 674, p = 0.66; epilepsy: 15 of 867 vs. six of 674, p = 0.16). Different forms of epilepsy were identified in both relatives of SMEI probands and controls. Twenty-eight relatives with FS and epilepsy were distributed in 20 (27%) of 74 SMEI families; among the controls, 18 affected relatives were clustered in 13 (18.5%) of 70 families. No pedigree showed several affected members, including the four with inherited mutations. CONCLUSIONS: A substantial epileptic family background is not present in our SMEI patients with SCN1A mutations. These data do not confirm previous observations and would not support polygenic inheritance in SMEI. The investigation of the family background in additional series of SMEI patients will further shed light on the genetics of this syndrome.
PURPOSE: The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25-70% of the patients having a family history of febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder. METHODS: We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families. Familial clustering and syndromic concordance within the affected relatives in both groups were investigated. RESULTS: The frequency of FS or epilepsy in relatives of SMEI patients did not significantly differ from that in controls (FS: 13 of 867 vs. 12 of 674, p = 0.66; epilepsy: 15 of 867 vs. six of 674, p = 0.16). Different forms of epilepsy were identified in both relatives of SMEI probands and controls. Twenty-eight relatives with FS and epilepsy were distributed in 20 (27%) of 74 SMEI families; among the controls, 18 affected relatives were clustered in 13 (18.5%) of 70 families. No pedigree showed several affected members, including the four with inherited mutations. CONCLUSIONS: A substantial epileptic family background is not present in our SMEI patients with SCN1A mutations. These data do not confirm previous observations and would not support polygenic inheritance in SMEI. The investigation of the family background in additional series of SMEI patients will further shed light on the genetics of this syndrome.
Authors: Rikke S Møller; Line H G Larsen; Katrine M Johannesen; Inga Talvik; Tiina Talvik; Ulvi Vaher; Maria J Miranda; Muhammad Farooq; Jens E K Nielsen; Lene Lavard Svendsen; Ditte B Kjelgaard; Karen M Linnet; Qin Hao; Peter Uldall; Mimoza Frangu; Niels Tommerup; Shahid M Baig; Uzma Abdullah; Alfred P Born; Pia Gellert; Marina Nikanorova; Kern Olofsson; Birgit Jepsen; Dragan Marjanovic; Lana I K Al-Zehhawi; Sofia J Peñalva; Bente Krag-Olsen; Klaus Brusgaard; Helle Hjalgrim; Guido Rubboli; Deb K Pal; Hans A Dahl Journal: Mol Syndromol Date: 2016-08-20
Authors: Steffen Syrbe; Boris S Zhorov; Astrid Bertsche; Matthias K Bernhard; Frauke Hornemann; Ulrike Mütze; Jessica Hoffmann; Konstanze Hörtnagel; Wieland Kiess; Franz W Hirsch; Johannes R Lemke; Andreas Merkenschlager Journal: Mol Syndromol Date: 2016-07-19
Authors: Claudia B Catarino; Joan Y W Liu; Ioannis Liagkouras; Vaneesha S Gibbons; Robyn W Labrum; Rachael Ellis; Cathy Woodward; Mary B Davis; Shelagh J Smith; J Helen Cross; Richard E Appleton; Simone C Yendle; Jacinta M McMahon; Susannah T Bellows; Thomas S Jacques; Sameer M Zuberi; Matthias J Koepp; Lillian Martinian; Ingrid E Scheffer; Maria Thom; Sanjay M Sisodiya Journal: Brain Date: 2011-06-29 Impact factor: 13.501