A novel clinical tool to classify facioscapulohumeral muscular dystrophy phenotypes

Giulia Ricci, Lucia Ruggiero, Liliana Vercelli, Francesco Sera, Ana Nikolic, Monica Govi, Fabiano Mele, Jessica Daolio, Corrado Angelini, Giovanni Antonini, Angela Lucia Berardinelli, Elisabetta Bucci, Michelangelo Cao, Maria Chiara D’Amico, Maria Grazia D'Angelo, A. Di Muzio, Massimiliano Filosto, Lorenzo Maggi, Maurizio Gualtiero Moggio, T. MonginiLucia Morandi, E. Pegoraro, C. Rodolico, Lucio Santoro, Gabriele Siciliano, Giuliano Tomelleri, Luisa Villa, Rossella Tupler

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Neurology
Publication statusAccepted/In press - Apr 28 2016


  • Clinical phenotype
  • Diagnostic criteria
  • Disease classification
  • Disease registry
  • FSHD

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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