Idiopathic dilated cardiomyopathy is a primary myocardial disease which is characterised by left ventricular, or biventricular, dilatation and impaired contractility. The precise aetiology is unknown and the relative contribution of genetic and environmental factors is debated. We report two identical male twins of Caucasian origin with idiopathic dilated cardiomyopathy who presented within a few months of each other.
- idiopathic dilated cardiomyopathy
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Two identical male twins were born in 1937. Both had unremarkable medical histories, with the exception of a hemi-thyroidectomy performed in the younger twin (by 20 minutes) for benign nodular goitre. In particular, neither twin had a history of hypertension, rheumatic heart disease, diabetes mellitus or any neuromuscular disorder. Neither took excessive alcohol or smoked tobacco. At no stage had either twin experienced anginal-type chest pain. Neither twin had previously received treatment with any cardiotoxic chemotherapeutic agents. The older twin had worked in the building industry, but there was no history of prolonged exposure to industrial toxins. There was a weak family history of ischaemic heart disease but not of cardiomyopathy.
The older twin presented in May 1995 with a one-week history of paroxysmal nocturnal dyspnoea. He was admitted to hospital. The findings on physical examination were an irregularly irregular pulse with a rate of 110 beats/min and a blood pressure of 140/80 mmHg. The central venous pressure was elevated and auscultation revealed normal heart sounds with no gallop, a pansystolic murmur and bibasal inspiratory crepitations. Chest X-ray revealed a normal cardiac size without evidence of frank pulmonary oedema. The electrocardiograph confirmed atrial fibrillation with a ventricular rate of 113 and no evidence of ischaemia or prior myocardial infarction. Full blood count, thyroid function tests and biochemical profile, including cardiac enzymes, were normal. Serum ferritin was at the low end of the normal range. The patient was treated to good effect with digoxin, diuretics and warfarin. Subsequent echocardiography revealed mild dilatation of the left ventricle (end-systolic internal dimension 4.3 cm, normal range 2.5–4.1 cm; end-diastolic internal dimension 5.7 cm, normal range 3.5–5.6 cm), incomplete co-aptation of the mitral valve cusps with an eccentric regurgitant jet and a dilated left atrium (diameter 4.0 cm, normal 1.9–3.8 cm). The calculated left ventricular ejection fraction was 40%. The echocardiographic appearances of the mitral valve suggested regurgitation secondary to myocardial pathology rather than a primary valve disorder.
Despite the introduction of angiotensin-converting enzyme (ACE) inhibitors, the patient's symptoms worsened and he was referred to the regional centre for cardiac catheterisation. This revealed minor coronary artery disease, with a 50% lesion in the second obtuse marginal branch and 10% lesions in the mid-right coronary artery and mid-left anterior descending artery. There was grade III mitral regurgitation with a left ventricular ejection fraction of 40%, end-diastolic pressure 18 mmHg and aortic pressure of 98/66 mmHg, mean 82 mmHg. There was moderate pulmonary hypertension, pulmonary artery pressure 44/18 mmHg, mean 30 mmHg. Histological examination of biopsy material from the left ventricle revealed subendocardial fibrosis, variation in myocyte size with some central vacuolation and no evidence of glycogen or iron storage abnormalities (figure). The findings were consistent with dilated cardiomyopathy.
The second twin presented in January 1996 with a short history of nocturnal cough and wheeze. This was associated with at least one episode of confirmed atrial fibrillation. He was admitted to hospital for investigation and treatment. Serial electrocardiographs confirmed paroxysmal atrial fibrillation and suggested left atrial dilatation. Echocardiography revealed left ventricular dilatation (end-systolic internal dimension 4.7 cm, end-diastolic internal dimension 5.4 cm), mild mitral regurgitation with a normal mitral valve appearances and dilatation of the left atrium (diameter 4.0 cm). The calculated left ventricular ejection fraction was 32%. There was mild left ventricular hypertrophy. Biochemical profile, thyroid function tests and full blood count were normal. Serum ferritin was at the low end of the normal range. Treatment was commenced with warfarin, diuretics, amiodarone and an ACE-inhibitor. He was referred to the regional centre for cardiac catheterisation and left ventricular biopsy. This revealed normal coronary arteries, a left ventricular ejection fraction of 38%, end-diastolic pressure 2/12 mmHg and aortic pressure of 112/65 mmHg, mean 82 mmHg. Pulmonary artery pressure was 27/12 mmHg, mean 18 mmHg. Histological examination of a biopsy specimen from the left ventricle revealed fibrosis, variation in cell size and some cells with central degenerative vacuoles. The findings were consistent with dilated cardiomyopathy.
Idiopathic dilated cardiomyopathy is not a rare condition. The estimated prevalence from studies in the US is 36.5 cases per 100 000 of the population1 with males more commonly affected than females and Afro-Caribbeans more than Caucasians.2 The reported 5-year survival rates are 50–80%, depending on the series.3 4 The condition is currently the most common indication worldwide for cardiac transplantation. Proposed pathogenetic mechanisms resulting in the disease include familial and genetic factors, chronic viral infection with resultant cardiac myocyte damage, and dysfunction of the immune system with autoimmune destruction of cardiac myocytes. It would seem likely that a number of factors combine to produce clinical disease in susceptible patients.
In recent years it has become apparent that familial disease is more important than was previously thought. Michels et al 5 studied 315 relatives from the families of 59 index cases with dilated cardiomyopathy, finding that 20.3% of index cases had an affected relative. In addition, 9.2% of healthy relatives with normal left ventricular ejection fractions had increased left ventricular dimensions during systole or diastole. Keelinget al 6 reported similar findings when studying 236 relatives from the families of 40 patients with dilated cardiomyopathy. In this study, 25 cases of dilated cardiomyopathy were identified among the relatives, of whom 22 were first degree relatives. The affected relatives all came from 10 (25%) of the 40 families screened. Amongst the apparently healthy relatives, 37 (18%) were found to have left ventricular enlargement.
The mode of inheritance in families with the condition is most commonly autosomal dominant. Genetic linkage analysis of a large family with familial dilated cardiomyopathy has indicated that the gene responsible for this condition is located on the long arm of chromosome 1 (1q32).7 However, four other specific gene loci for autosomal dominant dilated cardiomyopathy have also been described,8-11 indicating the genetically heterogenous nature of the condition. Autosomal recessive,12 X-linked recessive,13 and maternal inheritance through mitochondrial DNA have also been reported.14
To our knowledge, there has been only one published report of late-onset dilated cardiomyopathy in identical male twins.15 It is worth noting, however, that both these patients had maturity-onset non-insulin-dependent diabetes mellitus and one twin had hypertension.
The patients described here live close together in the same village. Therefore, it is possible that an environmental factor has played a part in the development of their similar cardiac conditions. In addition, the occurrence of dilated cardiomyopathy in members of the same family does not necessarily imply that the condition has a genetic basis. However, in the case of this pair of twins, the identical genetic profile and the onset of symptoms within a few months of each other would seem to imply that genetic factors in the aetiology of dilated cardiomyopathy are indeed more important than has been previously realised.
The authors acknowledge the assistance of Dr C Ritchie, Consultant Pathologist, Middlesbrough General Hospital, Middlesbrough.