BACKGROUND: Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures. OBJECTIVES: To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus. DESIGN: Observational family study. SETTING: The study was coordinated in a tertiary academic hospital, with data acquired in diverse primary, secondary, and tertiary care settings. PARTICIPANTS: Consenting members of a single large family. RESULTS: A 6-generation FAME kindred of European descent was ascertained in New Zealand and Australia. Affected family members (N = 55) had fine hand tremor, with onset typically in adolescence (median age, 15 years; age range, 4-60 years). Proximal myoclonus was present in 44 of 55 (80%), arising later than hand tremor (median age, 17 years; age range, 5-60 years). Generalized tonic-clonic seizures occurred in 8 of 55 (15%), with a median age at onset of 43.5 years (age range, 18-76 years). Neurophysiological testing confirmed features of cortical reflex myoclonus. Genetic mapping narrows the FAME2 (OMIM 607876) locus on chromosome 2 to a 13.3-megabase interval, harboring 99 known protein-coding genes. CONCLUSIONS: The most common FAME phenotype in this large family is mild postural hand tremor resembling essential tremor, combined with subtle proximal myoclonus. Generalized tonic-clonic seizures are uncommon and occur around sleep onset following severe generalized myoclonus.
BACKGROUND:Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures. OBJECTIVES: To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus. DESIGN: Observational family study. SETTING: The study was coordinated in a tertiary academic hospital, with data acquired in diverse primary, secondary, and tertiary care settings. PARTICIPANTS: Consenting members of a single large family. RESULTS: A 6-generation FAME kindred of European descent was ascertained in New Zealand and Australia. Affected family members (N = 55) had fine hand tremor, with onset typically in adolescence (median age, 15 years; age range, 4-60 years). Proximal myoclonus was present in 44 of 55 (80%), arising later than hand tremor (median age, 17 years; age range, 5-60 years). Generalized tonic-clonic seizures occurred in 8 of 55 (15%), with a median age at onset of 43.5 years (age range, 18-76 years). Neurophysiological testing confirmed features of cortical reflex myoclonus. Genetic mapping narrows the FAME2 (OMIM 607876) locus on chromosome 2 to a 13.3-megabase interval, harboring 99 known protein-coding genes. CONCLUSIONS: The most common FAME phenotype in this large family is mild postural hand tremor resembling essential tremor, combined with subtle proximal myoclonus. Generalized tonic-clonic seizures are uncommon and occur around sleep onset following severe generalized myoclonus.
Authors: Jose Felix Martí-Massó; Alberto Bergareche; Vladimir Makarov; Javier Ruiz-Martinez; Ana Gorostidi; Adolfo López de Munain; Juan Jose Poza; Pasquale Striano; Joseph D Buxbaum; Coro Paisán-Ruiz Journal: J Mol Med (Berl) Date: 2013-08-20 Impact factor: 4.599
Authors: Lyndal Henden; Saskia Freytag; Zaid Afawi; Sara Baldassari; Samuel F Berkovic; Francesca Bisulli; Laura Canafoglia; Giorgio Casari; Douglas Ewan Crompton; Christel Depienne; Jozef Gecz; Renzo Guerrini; Ingo Helbig; Edouard Hirsch; Boris Keren; Karl Martin Klein; Pierre Labauge; Eric LeGuern; Laura Licchetta; Davide Mei; Caroline Nava; Tommaso Pippucci; Gabrielle Rudolf; Ingrid Eileen Scheffer; Pasquale Striano; Paolo Tinuper; Federico Zara; Mark Corbett; Melanie Bahlo Journal: Hum Genet Date: 2016-07-01 Impact factor: 4.132
Authors: Tom van den Ende; Sarvi Sharifi; Sandra M A van der Salm; Anne-Fleur van Rootselaar Journal: Tremor Other Hyperkinet Mov (N Y) Date: 2018-01-23
Authors: Mark A Corbett; Thessa Kroes; Liana Veneziano; Mark F Bennett; Rahel Florian; Amy L Schneider; Antonietta Coppola; Laura Licchetta; Silvana Franceschetti; Antonio Suppa; Aaron Wenger; Davide Mei; Manuela Pendziwiat; Sabine Kaya; Massimo Delledonne; Rachel Straussberg; Luciano Xumerle; Brigid Regan; Douglas Crompton; Anne-Fleur van Rootselaar; Anthony Correll; Rachael Catford; Francesca Bisulli; Shreyasee Chakraborty; Sara Baldassari; Paolo Tinuper; Kirston Barton; Shaun Carswell; Martin Smith; Alfredo Berardelli; Renee Carroll; Alison Gardner; Kathryn L Friend; Ilan Blatt; Michele Iacomino; Carlo Di Bonaventura; Salvatore Striano; Julien Buratti; Boris Keren; Caroline Nava; Sylvie Forlani; Gabrielle Rudolf; Edouard Hirsch; Eric Leguern; Pierre Labauge; Simona Balestrini; Josemir W Sander; Zaid Afawi; Ingo Helbig; Hiroyuki Ishiura; Shoji Tsuji; Sanjay M Sisodiya; Giorgio Casari; Lynette G Sadleir; Riaan van Coller; Marina A J Tijssen; Karl Martin Klein; Arn M J M van den Maagdenberg; Federico Zara; Renzo Guerrini; Samuel F Berkovic; Tommaso Pippucci; Laura Canafoglia; Melanie Bahlo; Pasquale Striano; Ingrid E Scheffer; Francesco Brancati; Christel Depienne; Jozef Gecz Journal: Nat Commun Date: 2019-10-29 Impact factor: 14.919
Authors: Yongxing Zhou; Raman Sood; Qun Wang; Blake Carrington; Morgan Park; Alice C Young; Daniel Birnbaum; Zhao Liu; Tetsuo Ashizawa; James C Mullikin; Mohamad Z Koubeissi; Paul Liu Journal: Epilepsia Open Date: 2021-02-02