Motor and respiratory heterogeneity in Duchenne patients: Implication for clinical trials

• DOI: 10.1016/j.ejpn.2011.07.001
• Publication Date: 2011-09-15T22:36:42Z
• Authors: Véronique Humbert...; Dalil Hamroun; Kamel Bezzou; Carole Bérard; Odile Boespflug-T...; Christine Bommelaer; Emmanuelle Campan...; Claude Cances; Brigitte Chabrol; Marie-Christine C...; Jean-Marie Cuisset; Capucine de Lattre; Claude Desnuelle; Bernard Echenne; Cécile Halbert; Olivier Jonquet; Annick Labarre-Vila; Marie-Ange N’Guye...; Michel Pages; Jean-Louis Pepin; Thierry Petitjean; Jean Pouget; Elisabeth Ollagno...; Christian Richelme; François Rivier; Sabrina Sacconi; Vincent Tiffreau; Carole Vuillerot; Marie-Christine P...; Mireille Claustres; Christophe Béroud; Sylvie Tuffery-Gi...
• Keywords: Male; Adolescent; Movement; DNA Mutational Analysis; [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics; [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology; Dystrophin; 03 medical and health sciences; 0302 clinical medicine; 616; 617; Humans; Longitudinal Studies; Age of Onset; Child; Gait Disorders, Neurologic; [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]; Clinical Trials as Topic; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology; Molecular Biology/Molecular biology; 3. Good health; Muscular Dystrophy, Duchenne; Phenotype; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; Research Design; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry; Respiratory Mechanics; Female; France; [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]; Cardiomyopathies; Respiratory Insufficiency; Follow-Up Studies

Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD).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).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.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.