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Research paper
CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis
  1. V Fridman1,
  2. B Bundy2,
  3. M M Reilly3,
  4. D Pareyson4,
  5. C Bacon5,
  6. J Burns6,
  7. J Day7,
  8. S Feely5,8,
  9. R S Finkel9,
  10. T Grider5,
  11. C A Kirk2,
  12. D N Herrmann10,
  13. M Laurá3,
  14. J Li11,
  15. T Lloyd12,
  16. C J Sumner12,
  17. F Muntoni13,
  18. G Piscosquito4,
  19. S Ramchandren8,14,
  20. R Shy5,8,
  21. C E Siskind7,
  22. S W Yum15,16,
  23. I Moroni4,
  24. E Pagliano4,
  25. S Zuchner17,
  26. S S Scherer16,
  27. M E Shy5,8
  28. on behalf of the Inherited Neuropathies Consortium
  1. 1Departments of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2University of South Florida Epidemiology Center, Tampa, Florida, USA
  3. 3MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK
  4. 4Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy
  5. 5Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
  6. 6Departments of Neurology, University of Sydney & Children's Hospital, Sydney, Australia
  7. 7Departments of Neurology, Stanford University, Stanford, California, USA
  8. 8Departments of Neurology, Wayne State University, Detroit, Michigan, USA
  9. 9Departments of Neurology, Nemours Children's Hospital, Orlando, Florida, USA
  10. 10Departments of Neurology, University of Rochester, Rochester, New York, USA
  11. 11Departments of Neurology, Vanderbilt University, Nashville, Tennessee, USA
  12. 12Departments of Neurology, John Hopkins University, Baltimore, Maryland, USA
  13. 13Departments of Neurology, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK
  14. 14Departments of Neurology, University of Michigan, Ann Arbor, Michigan, USA
  15. 15Departments of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  16. 16Departments of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
  17. 17Departments of Neurology, Center for Human Molecular Genomics, University of Miami, Miami, Florida, USA
  1. Correspondence to Dr Vera Fridman, 165 Cambridge St. Boston, MA 02114, USA; vfridman{at}


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.

Clinical trial registration ID number NCT01193075.


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