Left ventricular dysfunction in duchenne muscular dystrophy and genotype

Abstract

Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded, and most deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene mutations might be predictive of either mild or severe cardiac dysfunction. We studied 75 patients with DMD followed at our institution. Cardiac function, as assessed by yearly echocardiography, showed marked variability in left ventricular (LV) function. Some patients in their 3rd decade had no or minimal dysfunction, whereas others in their 2nd decade had very severe dysfunction. Therefore, 4 severity groups were defined ranging from no or mild LV dysfunction to severe LV dysfunction using patient age at first abnormal echocardiographic finding and degree of LV dysfunction. Genetic data were collected for all patients. Most patients had mutations from exon 1 to 20 to exon 41 to 55. The distribution of the 4 severity groups of LV dysfunction did not significantly differ between these 2 mutation groups. An analysis based on the number of exons involved (<5 vs ≥5 exons) also found no significant difference in cardiac severity. When patients having identical mutations were compared with their cardiac course, concordance was often not evident. Steroid therapy had no apparent protection for the development of cardiomyopathy. In conclusion, 75 patients with DMD showed marked variability in the severity of LV dysfunction. Neither the age of onset nor the severity of cardiomyopathy correlated with any of the mutation groups.

Figure 1

Cumulative survival without echocardiographic evidence of cardiomyopathy as related to age. Note that not all patients with DMD have echocardiographic evidence of cardiomyopathy at age 25 years.

Figure 2

Shortening fraction (SF) as related to patient age. The patient’s age at their last normal echocardiogram is displayed for those patients with a persistently normal SF (SF ≥ 29). When patients had an abnormal SF, the age at the first abnormal SF is displayed. The distribution of patients with either normal SF or abnormal SF is unrelated to age. The variability of SF is marked.

Figure 3

Map of the mutations within each of the four Severity Groups. The exon numbers are shown at top. The length of each line corresponds to the number of involved exons. Note that the distributions of the exon mutations are similar for the 4 severity groups. Three patients had alterations above exon 55; 1 patient in severity class 1 (nonsense at exon 64), 1 patient in Severity Group 2 with a splice site mutation at exon 70 and 1 patient in Severity Group 3 with a deletion at exon 65.