The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis
Francesca Magri MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorVincenzo Nigro MD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorCorrado Angelini MD
Foundation S. Camillo Hospital, IRCCS, Lido, Venice, Italy
Search for more papers by this authorTiziana Mongini MD
Department of Neurosciences Rita Levi Montalcini, University of Torino, Torino, Italy
Search for more papers by this authorMarina Mora MD
Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorIsabella Moroni MD
Child Neurology Unit, IRCCS Foundation Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorAntonio Toscano MD
Department of Clinically and Experimental Medicine, University of Messina, Italy
Search for more papers by this authorMaria Grazia D'angelo MD, PhD
Neuromuscular Unit–IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy
Search for more papers by this authorGiuliano Tomelleri MD
Department of Neurological Sciences, Verona, Italy
Search for more papers by this authorGabriele Siciliano MD
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Search for more papers by this authorGiulia Ricci MD
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Search for more papers by this authorClaudio Bruno MD
Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova
Search for more papers by this authorStefania Corti MD, PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorOlimpia Musumeci MD
Department of Clinically and Experimental Medicine, University of Messina, Italy
Search for more papers by this authorGiorgio Tasca MD, PhD
Don Carlo Gnocchi ONLUS Foundation, Rome, Italy
Search for more papers by this authorEnzo Ricci MD, PhD
Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy
Search for more papers by this authorMauro Monforte MD
Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy
Search for more papers by this authorMonica Sciacco MD
Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorChiara Fiorillo MD
IRCCS Fondazione Stella Maris, Calambrone, Italy
Search for more papers by this authorSandra Gandossini MD
Neuromuscular Unit–IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy
Search for more papers by this authorCarlo Minetti MD
Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova
Search for more papers by this authorLucia Morandi MD
Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorMarco Savarese PhD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorGiuseppina Di Fruscio PhD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorClaudio Semplicini MD
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorElena Pegoraro MD
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorAlessandra Govoni MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorRoberta Brusa MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorRoberto Del Bo PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorDario Ronchi PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorMaurizio Moggio MD
Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorNereo Bresolin MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorCorresponding Author
Giacomo Pietro Comi MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Correspondence to: G.P. Comi; e-mail: [email protected]Search for more papers by this authorFrancesca Magri MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorVincenzo Nigro MD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorCorrado Angelini MD
Foundation S. Camillo Hospital, IRCCS, Lido, Venice, Italy
Search for more papers by this authorTiziana Mongini MD
Department of Neurosciences Rita Levi Montalcini, University of Torino, Torino, Italy
Search for more papers by this authorMarina Mora MD
Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorIsabella Moroni MD
Child Neurology Unit, IRCCS Foundation Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorAntonio Toscano MD
Department of Clinically and Experimental Medicine, University of Messina, Italy
Search for more papers by this authorMaria Grazia D'angelo MD, PhD
Neuromuscular Unit–IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy
Search for more papers by this authorGiuliano Tomelleri MD
Department of Neurological Sciences, Verona, Italy
Search for more papers by this authorGabriele Siciliano MD
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Search for more papers by this authorGiulia Ricci MD
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Search for more papers by this authorClaudio Bruno MD
Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova
Search for more papers by this authorStefania Corti MD, PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorOlimpia Musumeci MD
Department of Clinically and Experimental Medicine, University of Messina, Italy
Search for more papers by this authorGiorgio Tasca MD, PhD
Don Carlo Gnocchi ONLUS Foundation, Rome, Italy
Search for more papers by this authorEnzo Ricci MD, PhD
Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy
Search for more papers by this authorMauro Monforte MD
Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy
Search for more papers by this authorMonica Sciacco MD
Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorChiara Fiorillo MD
IRCCS Fondazione Stella Maris, Calambrone, Italy
Search for more papers by this authorSandra Gandossini MD
Neuromuscular Unit–IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy
Search for more papers by this authorCarlo Minetti MD
Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova
Search for more papers by this authorLucia Morandi MD
Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy
Search for more papers by this authorMarco Savarese PhD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorGiuseppina Di Fruscio PhD
Department of General Pathology, University of Naples, Naples, Italy
Telethon Institute of Genetics and Medicine, Naples, Italy
Search for more papers by this authorClaudio Semplicini MD
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorElena Pegoraro MD
Department of Neurosciences, University of Padua, Padua, Italy
Search for more papers by this authorAlessandra Govoni MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorRoberta Brusa MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorRoberto Del Bo PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorDario Ronchi PhD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorMaurizio Moggio MD
Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorNereo Bresolin MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Search for more papers by this authorCorresponding Author
Giacomo Pietro Comi MD
Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Correspondence to: G.P. Comi; e-mail: [email protected]Search for more papers by this authorThis study was supported by grants from Telethon (GUP10006 and GUP11006 to N.G.S.). Telethon Genetic Biobanks Network (GTB07001E) provided the DNA used in this study.
ABSTRACT
Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes. Methods: We created an Italian LGMD registry that included 370 molecularly defined patients. We reviewed detailed retrospective and prospective data and compared each LGMD subtype for differential diagnosis purposes. Results: LGMD types 2A and 2B are the most frequent forms in Italy. The ages at disease onset, clinical progression, and cardiac and respiratory involvement can vary greatly between each LGMD subtype. In a set of extensively studied patients, targeted next-generation sequencing (NGS) identified mutations in 36.5% of cases. Conclusion: Detailed clinical characterization combined with muscle tissue analysis is fundamental to guide differential diagnosis and to address molecular tests. NGS is useful for diagnosing forms without specific biomarkers, although, at least in our study cohort, several LGMD disease mechanisms remain to be identified. Muscle Nerve 55: 55–68, 2017
Supporting Information
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