Marked variation in the cardiomyopathy associated with Friedreich's ataxia

Objective-To document the cardiac phenotype associated with Friedreich's at axia, a recessively inherited disorder characterised by spinocerebellar deg eneration. Setting-Individuals with Friedreich's ataxia who accepted the invitation to participate in the study. Hypothesis-The cardiomyopathy associated with Friedreich's ataxia may offer a human model for the study of factors modulating cardiac hypertrophy. Methods-55 patients (mean (SD) age 30 (9) years) with a clinical diagnosis of Friedreich's ataxia were studied by clinical examination, electrocardiog raphy, cross sectional and Doppler echocardiography, and analysis of the GA A repeat in the first intron of the frataxin gene. Results-A wide variety of cardiac morphology was documented. Subjects with normal frataxin alleles had no evidence of cardiomyopathy. In homozygous su bjects, a relation was found between the thickness of the interventricular septum (r = 0.53, p < 0.005), left ventricular mass (r = 0.48, p < 0.01), a nd the number of GAA repeats on the smaller allele of the frataxin gene. No relation was shown between the presence of electrocardiographic abnormalit ies (mainly repolarisation changes) and either the pattern of ventricular h ypertrophy (if present) and degree of neurological disability or the length of time since diagnosis. No tendency to ventricular thinning or dilatation with age was found. Although ventricular systolic function appeared impair ed in some cases, Doppler studies of ventricular filling were within the no rmal range for age. Conclusions-The cardiomyopathy associated with Friedreich's ataxia shows a variable phenotype which is not concordant with the presence of ECG abnorma lities or the neurological features of the condition. As the genetic basis for Friedreich's ataxia has been established, further studies will help to clarify the molecular mechanisms of the cardiac Although appeared hypertrop hy.