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

AimsOur objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD).MethodsThe 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).ResultsMotor 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.ConclusionBeside 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.

► We study the phenotypic heterogeneity in Duchenne muscular dystrophy.
► The French DMD database provides clinical and molecular data of 278 patients.
► A severe DMD group has early severe motor and respiratory (but not heart) decline.
► Phenotypic heterogeneity must be considered in the design of clinical trials.
► Same efficacy will be detected by 4 to 6 times fewer patients from severe DMD form.