Familial Atrial Fibrillation
June 1, 1997 3 minutes read
Familial Atrial Fibrillation
ABSTRACT & COMMENTARY
Synopsis: Newer analytical techniques may permit identification of the genetic basis of an inherited disorder in a simpler, more timely manner and specific, genetically determined, or influenced alterations in structure or function may result in or contribute to the development of cardiac arrhythmias.
Source: Brugada R, et al. N Engl J Med 1997;336:905-911.
In this interesting paper, brugada and colleagues describe the identification of a genetic locus in three families with an inherited predisposition for atrial fibrillation. The initial family identified by the investigators included 26 members of a Spanish family, of whom nine were affected with atrial fibrillation in the absence of other forms of identifiable heart disease. Atrial fibrillation was observed to occur in autosomal dominant fashion through three generations of the family. Later, two other families who also had a familial pattern of atrial fibrillation were identified, and they are also included in this report.Brugada et al used a new technique for their analysis. They pooled DNA samples from affected vs. unaffected family members. This technique allowed them to identify the genetic locus for the disorder on chromosome 10q in the region of 10q22-q24. An identical pattern was seen in all three families. Because of the use of pooled samples for analysis, they were able to do this in a relatively short period of time with a small number of individuals. Individual DNA analyses were required for only 50 markers. Because of the great similarity in genetic markers identified in the three families, the authors believe that there must be some distant relationship between the families.
Brugada et al did not identify the specific gene or function responsible for paroxysmal atrial fibrillation in these families. They do mention that the genes for the beta adrenergic receptor, the alpha adrenergic receptor, and the G-protein-coupled receptor kinase are located on the 10q23-q26 segment. Further studies are planned to characterize fully the specific gene responsible for this syndrome.
COMMENT BY JOHN DiMARCO, MD, PhD
Atrial fibrillation remains a common and often perplexing clinical problem. In the vast majority of individuals, it arises in the setting of structural heart disease and either aging, atrial stretch, fibrosis, endocrine effects, or toxins can be identified as potential etiologies. However, there are individuals in whom all of these etiologies have been excluded, and, in these patients, some genetic predisposition toward atrial fibrillation might be involved. This predisposition might include changes in atrial structure or anatomy, alterations in intrinsic atrial electrophysiology, or different responses to hormonal, neural, or other physiologic influences. Any of these changes could be genetically based.Unfortunately, we are given little information about the clinical presentation of the subjects in these three families. One hopes that Brugada et al will fully describe this syndrome in a more clinically oriented format. It would be interesting to see if the presentation in these patients is similar to typical patients with lone or idiopathic atrial fibrillation encountered in clinical practice. Until we have more information, we can only speculate whether any abnormality identified in these three families will bear a relationship to the development in atrial fibrillation in large patient groups. For clinicians, this paper has two important messages. First, newer analytical techniques may permit identification of the genetic basis of an inherited disorder in a simpler, more timely manner. Second, specific, genetically determined, or influenced alterations in structure or function may result in or contribute to the development of cardiac arrhythmias.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content