December 2021; 7 (6) ArticleOpen Access
Progressive Myoclonus Epilepsies
Diagnostic Yield With Next-Generation Sequencing in Previously Unsolved Cases
View ORCID ProfileLaura Canafoglia, View ORCID ProfileSilvana Franceschetti, View ORCID ProfileAntonio Gambardella, View ORCID ProfilePasquale Striano, Anna Teresa Giallonardo, Paolo Tinuper, Carlo Di Bonaventura, Roberto Michelucci, Edoardo Ferlazzo, Tiziana Granata, Adriana Magaudda, Laura Licchetta, Alessandro Filla, Angela La Neve, Patrizia Riguzzi, Teresa Anna Cantisani, Martina Fanella, BARBARA CASTELLOTTI, Cinzia Gellera, View ORCID ProfileMelanie Bahlo, Federico Zara, Carolina Courage, View ORCID ProfileAnna-Elina Lehesjoki, View ORCID ProfileKaren L. Oliver, View ORCID ProfileSamuel F. Berkovic
First published November 12, 2021, DOI: https://doi.org/10.1212/NXG.0000000000000641
Laura Canafoglia
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Silvana Franceschetti
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Antonio Gambardella
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Pasquale Striano
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Anna Teresa Giallonardo
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Paolo Tinuper
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Carlo Di Bonaventura
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Roberto Michelucci
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Edoardo Ferlazzo
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Tiziana Granata
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Adriana Magaudda
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Laura Licchetta
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Alessandro Filla
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Angela La Neve
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Patrizia Riguzzi
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Teresa Anna Cantisani
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Martina Fanella
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
BARBARA CASTELLOTTI
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Cinzia Gellera
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Melanie Bahlo
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Federico Zara
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Carolina Courage
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Anna-Elina Lehesjoki
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Karen L. Oliver
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Samuel F. Berkovic
From the Neurophysiopathology (L.C., S.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Medical and Surgical Sciences (A.G., E.F.), Magna Graecia University, Catanzaro; IRCCS Istituto “G. Gaslini” (P.S., F.Z.), Genova; Department of Neurosciences (P.S., F.Z.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova; Department of Human Neurosciences (T.G., C.D.B., M.F.), Sapienza University of Rome, Viale dell'Università, Rome; IRCCS Istituto delle Scienze Neurologiche di Bologna (P.T., L.L.), Epilepsy Center, Bologna; Department of Biomedical and Neuromotor Sciences (P.T., L.L.), University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.M., P.R.), Unit of Neurology, Bellaria Hospital, Bologna; Regional Epilepsy Centre (E.F.), BMM Great Metropolitan Hospital, Via Melacrino, Reggio Calabria; Department of Pediatric Neuroscience (T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Epilepsy Center (A.M.), Department of Clinical and Experimental Medicine, AOU Policlinico “G. Martino”, Messina; Department of Neuroscience (A.F.), Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples; Department of Basic Medical Sciences (A.L.N.), Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari ; Perugia Hospital (T.A.C,), Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B.C., C.G.), IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Population Health and Immunity Division (M.B., K.L.O.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Department of Medical Biology (M.B., K.L.O.), The University of Melbourne; Folkhälsan Research Center (C.C., A.E.L.); Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland; and Epilepsy Research Centre (K.L.O., S.F.B), Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Progressive Myoclonus Epilepsies
Diagnostic Yield With Next-Generation Sequencing in Previously Unsolved Cases
Laura Canafoglia, Silvana Franceschetti, Antonio Gambardella, Pasquale Striano, Anna Teresa Giallonardo, Paolo Tinuper, Carlo Di Bonaventura, Roberto Michelucci, Edoardo Ferlazzo, Tiziana Granata, Adriana Magaudda, Laura Licchetta, Alessandro Filla, Angela La Neve, Patrizia Riguzzi, Teresa Anna Cantisani, Martina Fanella, BARBARA CASTELLOTTI, Cinzia Gellera, Melanie Bahlo, Federico Zara, Carolina Courage, Anna-Elina Lehesjoki, Karen L. Oliver, Samuel F. Berkovic
Neurol Genet Dec 2021, 7 (6) e641; DOI: 10.1212/NXG.0000000000000641
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Abstract
Background and Objectives To assess the current diagnostic yield of genetic testing for the progressive myoclonus epilepsies (PMEs) of an Italian series described in 2014 where Unverricht-Lundborg and Lafora diseases accounted for ∼50% of the cohort.
Methods Of 47/165 unrelated patients with PME of indeterminate genetic origin, 38 underwent new molecular evaluations. Various next-generation sequencing (NGS) techniques were applied including gene panel analysis (n = 7) and/or whole-exome sequencing (WES) (WES singleton n = 29, WES trio n = 7, and WES sibling n = 4). In 1 family, homozygosity mapping was followed by targeted NGS. Clinically, the patients were grouped in 4 phenotypic categories: “Unverricht-Lundborg disease-like PME,” “late-onset PME,” “PME plus developmental delay,” and “PME plus dementia.”
Results Sixteen of 38 (42%) unrelated patients reached a positive diagnosis, increasing the overall proportion of solved families in the total series from 72% to 82%. Likely pathogenic variants were identified in NEU1 (2 families), CERS1 (1 family), and in 13 nonfamilial patients in KCNC1 (3), DHDDS (3), SACS, CACNA2D2, STUB1, AFG3L2, CLN6, NAXE, and CHD2. Across the different phenotypic categories, the diagnostic rate was similar, and the same gene could be found in different phenotypic categories.
Discussion The application of NGS technology to unsolved patients with PME has revealed a collection of very rare genetic causes. Pathogenic variants were detected in both established PME genes and in genes not previously associated with PME, but with progressive ataxia or with developmental encephalopathies. With a diagnostic yield >80%, PME is one of the best genetically defined epilepsy syndromes.
Glossary
- NGS=
- next-generation sequencing;
- PME=
- progressive myoclonus epilepsy;
- ULD=
- Unverricht-Lundborg disease;
- WES=
- whole-exome sequencing
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by C. Besta Institute, Health Italian Ministry.
- Received August 20, 2021.
- Accepted in final form October 8, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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