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Familial idiopathic congestive cardiomyopathy in three generations: a family study with eight affected members
B A MacLennan1, E Y Tsoi, C Maguire
1Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland.
Insights
This study identifies an autosomal dominant inherited dilated cardiomyopathy in a large family. The disease shows a malignant course, with early onset and rapid progression to cardiac failure or sudden death.
Area of Science:
- Cardiology
- Genetics
- Pathology
Background:
- Idiopathic congestive (dilated) cardiomyopathy (DCM) can have genetic underpinnings.
- Autosomal dominant inheritance patterns are observed in some forms of DCM.
- Understanding the clinical course and genetic basis of DCM is crucial for patient management.
Observation:
- A kindred of 63 non-consanguineous individuals exhibited DCM across three generations.
- Eight individuals were affected, with presentation typically in adulthood (average age 39.5 years).
- Histological examination revealed varying muscle fiber size and interstitial fibrosis.
Findings:
- The disease followed a malignant course, leading to relentless cardiac failure in six individuals.
- Sudden death occurred in three cases, including one asymptomatic individual.
- Prospective evaluation of 42 family members revealed murmurs, conduction abnormalities, and echocardiographic findings suggestive of early-stage disease.
Implications:
- This family study highlights a specific autosomal dominant form of DCM with a poor prognosis.
- Early detection through genetic screening and cardiac evaluation is vital for at-risk family members.
- Cardiac transplantation is a potential therapeutic option for younger patients with severe, unremitting disease.
Abstract:
Idiopathic congestive (dilated) cardiomyopathy with an autosomal dominant inheritance pattern affected eight individuals (four males) in three of four generations of a 63-member kindred of non-consanguineous ancestry. Average age at presentation was 39.5 years (range 32-54). A malignant course with relentless cardiac failure occurred in six cases; one member who died suddenly had been asymptomatic and the eighth is alive but in cardiac failure 44 months after initial presentation. Average time course to death from onset of symptoms suggestive of cardiomyopathy in six affected members was 16 months (range three to 55 months). In three cases, sudden death occurred and was the mode of presentation in one. Myocardial histological examination, available from three cases, showed variation in muscle fibre size with interstitial fibrosis. Forty-two family members in two generations including the propositus (19 males), age range three to 46 years (mean 17.9) when first assessed were prospectively evaluated. Two had basal systolic murmurs and two had right bundle branch block. Excluding the propositus, three members showed Doppler echocardiographic evidence of regurgitation without associated structural anomalies and three had valve prolapse with Doppler echocardiographic evidence of regurgitation. Cardiac chamber dimensions were within normal limits in all members and no cardiac arrhythmias were seen. Among the various therapeutic approaches now available cardiac transplantation, especially in younger patients with unremitting disease, is a potential option which should be considered.