title: CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.
abstract: BACKGROUND
  The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them.
  
  
  METHODS
  We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES).
  
  
  RESULTS
  997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported.
  
  
  CONCLUSIONS
  Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT.
  
  
  BACKGROUND
  ID number NCT01193075.
authors.affiliation: Departments of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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authors.lastname: Fridman
authors.affiliation: University of South Florida Epidemiology Center, Tampa, Florida, USA.
authors.forename: B
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authors.lastname: Bundy
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Reilly
authors.affiliation: Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pareyson
authors.affiliation: Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
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authors.affiliation: Departments of Neurology, University of Sydney & Children's Hospital, Sydney, Australia.
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authors.affiliation: Departments of Neurology, Stanford University, Stanford, California, USA.
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authors.affiliation: Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA Departments of Neurology, Wayne State University, Detroit, Michigan, USA.
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authors.lastname: Feely
authors.affiliation: Departments of Neurology, Nemours Children's Hospital, Orlando, Florida, USA.
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authors.affiliation: Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
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authors.lastname: Grider
authors.affiliation: University of South Florida Epidemiology Center, Tampa, Florida, USA.
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authors.affiliation: Departments of Neurology, University of Rochester, Rochester, New York, USA.
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authors.initials: DN
authors.lastname: Herrmann
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
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authors.lastname: Laurá
authors.affiliation: Departments of Neurology, Vanderbilt University, Nashville, Tennessee, USA.
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authors.affiliation: Departments of Neurology, John Hopkins University, Baltimore, Maryland, USA.
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authors.lastname: Lloyd
authors.affiliation: Departments of Neurology, John Hopkins University, Baltimore, Maryland, USA.
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authors.initials: CJ
authors.lastname: Sumner
authors.affiliation: Departments of Neurology, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: G
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authors.lastname: Piscosquito
authors.affiliation: Departments of Neurology, Wayne State University, Detroit, Michigan, USA Departments of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-4346-5719
authors.initials: S
authors.lastname: Ramchandren
authors.affiliation: Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA Departments of Neurology, Wayne State University, Detroit, Michigan, USA.
authors.forename: R
authors.initials: R
authors.lastname: Shy
authors.affiliation: Departments of Neurology, Stanford University, Stanford, California, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Siskind
authors.affiliation: Departments of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Departments of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Yum
authors.affiliation: Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Moroni
authors.affiliation: Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pagliano
authors.affiliation: Departments of Neurology, Center for Human Molecular Genomics, University of Miami, Miami, Florida, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zuchner
authors.affiliation: Departments of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Scherer
authors.affiliation: Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA Departments of Neurology, Wayne State University, Detroit, Michigan, USA.
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authors.initials: ME
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002607:Charcot-Marie-Tooth Disease / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017630:Connexins / Q000235:genetics; D017281:Cost of Illness; D003430:Cross-Sectional Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D018993:Myelin P0 Protein / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D000097002:Gap Junction beta-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D017630:Connexins; D020558:GTP Phosphohydrolases; D024101:Mitochondrial Proteins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D009687:Nuclear Proteins; D011506:Proteins; D000097002:Gap Junction beta-1 Protein; C109561:CDRT1 protein, human; C470309:MAD2L1BP protein, human; C560547:MPZ protein, human; C073687:PMP22 protein, human; C470018:MFN2 protein, human
keywords: GENETICS; NEUROGENETICS; NEUROPATHY