Cardiopulmonary phenotypic discordance is common in Duchenne muscular dystrophy

To determine the prevalence of discordant cardiopulmonary function among patients with Duchenne muscular dystrophy (DMD) in our clinic.

Retrospective chart review from 1999 to 2017.

DMD patients age ≥ 18 years, alive, with discordant cardiopulmonary function. No patients received glucocorticoid therapy. Discordant cardiopulmonary function was defined as either: good heart function (EF ≥ 40%) and bad lung function (FVC < 1 L) (Group A); or, bad heart function (EF < 40%) and good lung function (FVC ≥ 1 L) (Group B).

Among 74 eligible patients, 25 patients (34%) had discordant cardiopulmonary function (21 patients in Group A and 4 patients in Group B). Three dystrophin mutations were shared by >2 patients (nine patients with deletion of exon 44; three patients with deletion of exon 51; three patients with duplication of exon 2). Among the 15 patients with a shared genotype, eight patients (53%) had discordant cardiopulmonary function (five patients in group A, three patients in group B). Twenty-six patients had a deletion involving or distal to exon 45. Ten of these patients (38%) had discordant cardiopulmonary function (eight patients in Group A, two patients in Group B).

In our cohort of DMD patients, discordant cardiopulmonary function was common (present in one-third of our patients), and the dystrophin genotype did not reliably predict a patient's cardiopulmonary phenotype. If confirmed by larger, multi-center studies, our findings have significant implications for predicting patient prognosis, evaluating DMD therapies, and designing new DMD therapies.