Marked variation in the cardiomyopathy associated with Friedreich's ataxia
D P Dutka1, J E Donnelly, P Nihoyannopoulos
1National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. d.dutka@rpms.ac.uk
Insights
Friedreich's ataxia (FA) can cause variable cardiomyopathy. The severity of cardiac hypertrophy in FA patients correlates with the number of GAA repeats in the frataxin gene, not neurological disability.
Area of Science:
- Cardiology
- Genetics
- Neurology
Background:
- Friedreich's ataxia (FA) is a recessively inherited neurodegenerative disorder.
- Cardiac involvement, specifically cardiomyopathy, is a common and serious complication of FA.
Purpose of the Study:
- To document the cardiac phenotype in patients with Friedreich's ataxia.
- To investigate the relationship between genetic factors, cardiac morphology, and clinical features in FA.
Main Methods:
- Studied 55 patients diagnosed with Friedreich's ataxia.
- Utilized clinical examination, electrocardiography, echocardiography, and genetic analysis of the frataxin gene (GAA repeat expansion).
Main Results:
- Cardiac hypertrophy, particularly interventricular septum thickening and increased left ventricular mass, was observed in FA patients.
- A significant correlation was found between the number of GAA repeats in the frataxin gene and the degree of cardiac hypertrophy.
- No correlation was found between cardiac abnormalities and electrocardiographic findings, neurological disability, or disease duration.
Conclusions:
- The cardiomyopathy in Friedreich's ataxia exhibits a variable phenotype.
- Cardiac hypertrophy in FA is primarily linked to the genetic mutation, independent of neurological progression or ECG changes.
- Further research into the molecular mechanisms of cardiac hypertrophy in FA is warranted.
Objective:
To document the cardiac phenotype associated with Friedreich's ataxia, a recessively inherited disorder characterised by spinocerebellar degeneration.
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, electrocardiography, cross sectional and Doppler echocardiography, and analysis of the GAA 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 subjects, 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), and the number of GAA repeats on the smaller allele of the frataxin gene. No relation was shown between the presence of electrocardiographic abnormalities (mainly repolarisation changes) and either the pattern of ventricular hypertrophy (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 impaired in some cases, Doppler studies of ventricular filling were within the normal range for age.
Conclusions:
The cardiomyopathy associated with Friedreich's ataxia shows a variable phenotype which is not concordant with the presence of ECG abnormalities 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 hypertrophy.
Related Concept Videos
01:21Myocarditis I: Introduction
01:23Rheumatic Heart Disease I: Introduction
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:11Alterations in Muscle Tone lll