title: A novel clinical tool to classify facioscapulohumeral muscular dystrophy phenotypes.
abstract: Based on the 7-year experience of the Italian Clinical Network for FSHD, we revised the FSHD clinical form to describe, in a harmonized manner, the phenotypic spectrum observed in FSHD. The new Comprehensive Clinical Evaluation Form (CCEF) defines various clinical categories by the combination of different features. The inter-rater reproducibility of the CCEF was assessed between two examiners using kappa statistics by evaluating 56 subjects carrying the molecular marker used for FSHD diagnosis. The CCEF classifies: (1) subjects presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1-A3), (2) subjects with muscle weakness limited to scapular girdle or facial muscles (category B subcategories B1, B2), (3) asymptomatic/healthy subjects (category C, subcategories C1, C2), (4) subjects with myopathic phenotype presenting clinical features not consistent with FSHD canonical phenotype (D, subcategories D1, D2). The inter-rater reliability study showed an excellent concordance of the final four CCEF categories with a κ equal to 0.90; 95 % CI (0.71; 0.97). Absolute agreement was observed for categories C and D, an excellent agreement for categories A [κ = 0.88; 95 % CI (0.75; 1.00)], and a good agreement for categories B [κ = 0.79; 95 % CI (0.57; 1.00)]. The CCEF supports the harmonized phenotypic classification of patients and families. The categories outlined by the CCEF may assist diagnosis, genetic counseling and natural history studies. Furthermore, the CCEF categories could support selection of patients in randomized clinical trials. This precise categorization might also promote the search of genetic factor(s) contributing to the phenotypic spectrum of disease.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.|Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ruggiero
authors.affiliation: Department of Neuroscience, Center for Neuromuscular Diseases, University of Turin, Turin, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Vercelli
authors.affiliation: MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Govi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Mele
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Daolio
authors.affiliation: IRCCS San Camillo, Venice, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Department of Neuroscience, Mental Health and Sensory Organs, S. Andrea Hospital, University of Rome "Sapienza", Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Antonini
authors.affiliation: Unit of Child Neurology and Psychiatry, IRCCS "C. Mondino" Foundation, Pavia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Berardinelli
authors.affiliation: Department of Neuroscience, Mental Health and Sensory Organs, S. Andrea Hospital, University of Rome "Sapienza", Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bucci
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cao
authors.affiliation: Center for Neuromuscular Disease, CeSI, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: D'Amico
authors.affiliation: Department of Neurorehabilitation, IRCCS Institute Eugenio Medea, Bosisio Parini, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Angelo
authors.affiliation: Center for Neuromuscular Disease, CeSI, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Muzio
authors.affiliation: Neurology Clinic, ''Spedali Civili'' Hospital, Brescia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.affiliation: IRCCS Foundation, C. Besta Neurological Institute, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Neuromuscular Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, University of Milan, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.affiliation: Department of Neuroscience, Center for Neuromuscular Diseases, University of Turin, Turin, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mongini
authors.affiliation: IRCCS Foundation, C. Besta Neurological Institute, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rodolico
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tomelleri
authors.affiliation: Neuromuscular Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, University of Milan, Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Villa
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. rossella.tupler@unimore.it.|Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, USA. rossella.tupler@unimore.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: Tupler
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D053580:Muscle Strength; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000145:classification* / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D009460:Neurologic Examination; D015588:Observer Variation; D010641:Phenotype; D012042:Registries
keywords: Clinical phenotype; Diagnostic criteria; Disease classification; Disease registry; FSHD