Early cardiac and autonomic markers and their genotype-phenotype associations in Duchenne muscular dystrophy.

INTRODUCTION

Duchenne muscular dystrophy (DMD), an X-linked disorder due to dystrophin gene mutations leads to progressive muscle weakness and ambulation loss by adolescence. Autonomic dysfunction precedes dilated cardiomyopathy, a major cause of mortality. This study aimed to investigate early cardiovascular markers and their genotype - phenotype associations in young DMD patients.

METHODS

Genetically confirmed ambulant DMD boys (n = 66) aged 5-10 years recruited from a quaternary care centre for neurological disorders in Southern India, were subjected to HRV, electrocardiography and compared with controls (n = 46 and n = 31 respectively) while echocardiography measures were compared with normative data. Relevant genotype - phenotype associations were evaluated.

RESULTS

DMD subjects' HRV measures showed significantly higher LFnu, LF/HF and lower SDNN, RMSSD, total power compared to controls, and significantly shortened PR, prolonged QTc, greater Q, S, R wave amplitudes. Significantly higher E, E/A; and significantly lower LVEF, LVID (d), LVID(s), IVS (d) were found in DMD subjects. Further, HR and LF were positively correlated with time to rise from supine (p = 0.002 and p = 0.008 respectively) and HR with time to climb four standard stairs (p = 0.005). Genotype-phenotype correlations revealed more cardiac dysfunction with greater Q amplitude and lesser E, A velocities in proximal mutation group (exons1-44) than distal (exons45-79).

DISCUSSION/

CONCLUSIONS

Reduced HRV with increased sympathetic and decreased parasympathetic activity was found in DMD subjects. Significant abnormalities in cardiac investigations suggest initiation of early cardiac involvement in younger DMD patients. Significant associations between cardiac autonomic, functional and genotype highlight the need for further research to explore these relationships in depth.