title: Motor and respiratory heterogeneity in Duchenne patients: implication for clinical trials.
abstract: OBJECTIVE
  Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD).
  
  
  METHODS
  The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years). Diagnosis was based on mutation identification in the DMD gene. Three groups were defined according to the age at ambulation loss: before 8 years (group A); between 8 and 11 years (group B); between 11 and 16 years (group C).
  
  
  RESULTS
  Motor and respiratory declines were statistically different between the three groups, as opposed to heart involvement. When acquired, running ability was lost at the mean age of 5.41 (group A), 7.11 (group B), 9.19 (group C) years; climbing stairs ability at 6.24 (group A), 7.99 (group B), 10,42 (group C) years, and ambulation at 7.10 (group A), 9.25 (group B), 12.01 (group C) years. Pulmonary growth stopped at 10.26 (group A), 12.45 (group B), 14.58 (group C) years. Then, forced vital capacity decreased at the rate of 8.83 (group A), 7.52 (group B), 6.03 (group C) percent per year. Phenotypic variability did not rely on specific mutational spectrum.
  
  
  CONCLUSIONS
  Beside the most common form of DMD (group B), we provide detailed description on two extreme clinical subgroups: a severe one (group A) characterized by early severe motor and respiratory decline and a milder subgroup (group C). Compared to group B or C, four to six times fewer patients from group A are needed to detect the same decrease in disease progression in a clinical trial.
authors.affiliation: CHU Montpellier, Laboratoire de Génétique Moléculaire, Montpellier, F-34000, France. veronique.humbertclaude@inserm.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Humbertclaude
authors.forename: Dalil
authors.initials: D
authors.lastname: Hamroun
authors.forename: Kamel
authors.initials: K
authors.lastname: Bezzou
authors.forename: Carole
authors.initials: C
authors.lastname: Bérard
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: Christine
authors.initials: C
authors.lastname: Bommelaer
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Campana-Salort
authors.forename: Claude
authors.initials: C
authors.lastname: Cances
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Commare
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.forename: Capucine
authors.initials: C
authors.lastname: de Lattre
authors.forename: Claude
authors.initials: C
authors.lastname: Desnuelle
authors.forename: Bernard
authors.initials: B
authors.lastname: Echenne
authors.forename: Cécile
authors.initials: C
authors.lastname: Halbert
authors.forename: Olivier
authors.initials: O
authors.lastname: Jonquet
authors.forename: Annick
authors.initials: A
authors.lastname: Labarre-Vila
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: N'Guyen-Morel
authors.forename: Michel
authors.initials: M
authors.lastname: Pages
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pepin
authors.forename: Thierry
authors.initials: T
authors.lastname: Petitjean
authors.forename: Jean
authors.initials: J
authors.lastname: Pouget
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ollagnon-Roman
authors.forename: Christian
authors.initials: C
authors.lastname: Richelme
authors.forename: François
authors.initials: F
authors.lastname: Rivier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sacconi
authors.forename: Vincent
authors.initials: V
authors.lastname: Tiffreau
authors.forename: Carole
authors.initials: C
authors.lastname: Vuillerot
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Picot
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tuffery-Giraud
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D009202:Cardiomyopathies / Q000209:etiology; D002648:Child; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005602:France; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009068:Movement / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D012107:Research Design; D012131:Respiratory Insufficiency / Q000209:etiology; D015656:Respiratory Mechanics / Q000502:physiology*; D012600:Scoliosis / Q000209:etiology; D013534:Survival; D014797:Vital Capacity / Q000502:physiology
chemical_list: D016189:Dystrophin