title: The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Magri
authors.affiliation: Department of General Pathology, University of Naples, Naples, Italy.|Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
authors.affiliation: Foundation S. Camillo Hospital, IRCCS, Lido, Venice, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Department of Neurosciences Rita Levi Montalcini, University of Torino, Torino, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mongini
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
authors.affiliation: Child Neurology Unit, IRCCS Foundation Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.affiliation: Department of Clinically and Experimental Medicine, University of Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.affiliation: Neuromuscular Unit-IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: D'angelo
authors.affiliation: Department of Neurological Sciences, Verona, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tomelleri
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.affiliation: 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.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.affiliation: Department of Clinically and Experimental Medicine, University of Messina, Italy.
authors.forename: Olimpia
authors.initials: O
authors.lastname: Musumeci
authors.affiliation: Don Carlo Gnocchi ONLUS Foundation, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tasca
authors.affiliation: Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.affiliation: Department of Neurology, Policlinico Universitario A. Gemelli, University Cattolica del Sacro Cuore of Rome, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Monforte
authors.affiliation: Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Sciacco
authors.affiliation: IRCCS Fondazione Stella Maris, Calambrone, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorillo
authors.affiliation: Neuromuscular Unit-IRCCS E. Medea Bosisio Parini, Bosisio Parini, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gandossini
authors.affiliation: Center of Myology and Neurodegenerative Diseases, Istituto Giannina Gaslini, Genova.
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Department of General Pathology, University of Naples, Naples, Italy.|Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Savarese
authors.affiliation: Department of General Pathology, University of Naples, Naples, Italy.|Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Giuseppina Di
authors.initials: GD
authors.lastname: Fruscio
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Semplicini
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Govoni
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Brusa
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.affiliation: 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.
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.affiliation: Dino Ferrari Centre, Neuromuscular and Rare Diseases Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.affiliation: 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.
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.affiliation: 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.
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D003402:Creatine Kinase / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D012042:Registries; D012120:Respiration Disorders / Q000209:etiology; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; D003402:Creatine Kinase
keywords: differential diagnosis; genotype-phenotype correlations; limb girdle muscular dystrophy; natural history; next-generation sequencing