Journal article
CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis
Journal of neurology, neurosurgery and psychiatry, Vol.86(8), pp.873-878
08/2015
DOI: 10.1136/jnnp-2014-308826
PMCID: PMC4516002
PMID: 25430934
Abstract
BackgroundThe 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.MethodsWe 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).Results997 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.ConclusionsOur 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 registrationID number NCT01193075.
Details
- Title: Subtitle
- CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis
- Creators
- V Fridman - Departments of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USAB Bundy - University of South Florida Epidemiology Center, Tampa, Florida, USAM M Reilly - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UKD Pareyson - Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, ItalyC Bacon - Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAJ Burns - Departments of Neurology, University of Sydney & Children's Hospital, Sydney, AustraliaJ Day - Departments of Neurology, Stanford University, Stanford, California, USAS Feely - Departments of Neurology, Wayne State University, Detroit, Michigan, USAR S Finkel - Departments of Neurology, Nemours Children's Hospital, Orlando, Florida, USAT Grider - Departments of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAC A Kirk - University of South Florida Epidemiology Center, Tampa, Florida, USAD N Herrmann - Departments of Neurology, University of Rochester, Rochester, New York, USAM Laurá - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UKJ Li - Departments of Neurology, Vanderbilt University, Nashville, Tennessee, USAT Lloyd - Departments of Neurology, John Hopkins University, Baltimore, Maryland, USAC J Sumner - Departments of Neurology, John Hopkins University, Baltimore, Maryland, USAF Muntoni - Departments of Neurology, UCL Institute of Child Health & Great Ormond Street Hospital, London, UKG Piscosquito - Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, ItalyS Ramchandren - Departments of Neurology, University of Michigan, Ann Arbor, Michigan, USAR Shy - Departments of Neurology, Wayne State University, Detroit, Michigan, USAC E Siskind - Departments of Neurology, Stanford University, Stanford, California, USAS W Yum - Departments of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USAI Moroni - Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, ItalyE Pagliano - Departments of Neurology, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, ItalyS Zuchner - Departments of Neurology, Center for Human Molecular Genomics, University of Miami, Miami, Florida, USAS S Scherer - Departments of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USAM E Shy - Departments of Neurology, Wayne State University, Detroit, Michigan, USA
- Resource Type
- Journal article
- Publication Details
- Journal of neurology, neurosurgery and psychiatry, Vol.86(8), pp.873-878
- DOI
- 10.1136/jnnp-2014-308826
- PMID
- 25430934
- PMCID
- PMC4516002
- NLM abbreviation
- J Neurol Neurosurg Psychiatry
- ISSN
- 0022-3050
- eISSN
- 1468-330X
- Language
- English
- Date published
- 08/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020795502771
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