A total of 94 patients with DMD formed the study cohort that was divided into 2 groups. 67 patients (71 %) were in the confirmed molecular diagnosis group, 27 patients (29 %) were in the clinical diagnosis only group. This division was made to ensure that milder types of muscular dystrophy would not confound the survival statistics of the first group.
For the cohort of 67 patients, median age at diagnosis was 4.0 years (range 0-10). They achieved independent ambulation at a median age of 15.5 months (range 9-48). The median age of first wheelchair use was 10.0 years (range 6-15) for the 67 boys. Ventilation was introduced at a median age of 20.0 years (range 9-30). There was a significant correlation between age of getting the first wheelchair and age of death (p = 0.016 Pearsons r, 0.383).
The probability of surviving to at least the age of 24 years was 67 % for patients with clinical diagnosis only. Without molecular testing, we cannot rule out milder forms like Becker type of muscular dystrophy among this patient cohort. The probability of reaching 24 years was 50 % for subjects with DMD diagnosed on a molecular level. This group included 67 patients with a proven outof- frame mutation.
Previous reports showed exceptions to the readingframe rule concerning deletions (18
) and duplications (24
). In these cases of exceptional out-of-frame mutations, there is a partly functional dystrophin protein that normally occurs in the Becker muscular dystrophy (BMD) as a consequence of an in-frame mutation. To verify 18 deletions and 10 duplications, former findings of muscle biopsy were considered. Due to the lack of information about the gene product in the findings, it was not possible to make a statement on the course of the disease. As there was no statistically significant difference between the possible exceptions and the remaining out-of-frame mutations, no possible exception mutation was excluded.
Patients diagnosed on the molecular level had a median survival of 24.0 years (95 % confidence interval 21.3-26.7 years) (). It is estimated to be the most important result of this study, since up to now such data have not been available in Germany. Among medical intervention, ventilation emerged as the most significant life-prolonging measure. The median survival of nonventilated patients was 19.0 years (95 % confidence interval 17.7-20.3 years) compared to 27.0 years for those who were ventilated (95 % confidence interval 20.2-33.8 Jahre). As shown in , there was a statistically significant difference between the respective survival curves (Log rank p < 0,001).
Figure 1. Survival curves (Kaplan Meier) for two patient cohorts. The green line shows percentage survival for 67 patients with molecularly proven diagnosis. The blue line reflects percentage survival for 27 patients with clinical diagnosis only (p = 0.028, log (more ...)
Figure 2. Survival curves (Kaplan Meier) for ventilated versus non-ventilated patients diagnosed at the molecular level. The green line denotes percentage survival for 44 ventilated patients. Information about details of ventilation is not available. The blue line (more ...)