Recurrence of atrial septal defect in three generations
C Ferreira1, L M Farah, R M Póvoa
1Universidade Federal de São Paulo, EPM, Brazil.
Insights
This study investigates familial atrial septal defects (ASD), revealing an autosomal recessive inheritance pattern. Early genetic screening is crucial for detecting asymptomatic carriers and ensuring timely treatment for affected individuals.
Area of Science:
- Cardiology
- Genetics
- Pediatric Medicine
Background:
- Atrial septal defect (ASD) of the secundum type can exhibit familial clustering.
- Previous studies suggested an autosomal recessive transmission for ASD in this family.
- The identification of a fifth affected individual prompted re-evaluation of the genetic mechanism.
Purpose of the Study:
- To elucidate the genetic transmission patterns of secundum atrial septal defects within a multi-generational family.
- To investigate potential alternative genetic mechanisms, such as uniparental disomy, in familial ASD.
- To emphasize the importance of genetic-clinical studies for early detection of asymptomatic ASD carriers.
Main Methods:
- Genealogical investigation of affected individuals across three generations.
- Clinical confirmation of atrial septal defects.
- Analysis of family history, consanguinity, and parental phenotypes.
- Consideration of genetic mechanisms including autosomal recessive inheritance and uniparental disomy.
Main Results:
- Four individuals across three generations presented with anatomically similar secundum ASDs.
- An autosomal recessive transmission pattern was initially proposed.
- A fifth affected individual, born to non-consanguineous parents (one being a family member), suggested possible uniparental disomy or a complex inheritance pattern.
- Parents of the fifth individual were phenotypically normal, highlighting the challenge of carrier detection.
Conclusions:
- Familial occurrence of secundum ASD can be driven by complex genetic mechanisms.
- Autosomal recessive inheritance and uniparental disomy are potential explanations for ASD recurrence in this family.
- Genetic-clinical studies are essential for identifying asymptomatic carriers within affected families.
- Early detection and intervention are critical for individuals with familial ASD.
Abstract:
Beginning with a patient presenting with an atrial septal defect (ASD) of the secundum type, the genealogy was identified in four affected individuals who belonged to three successive generations of the same family. The defects were visually confirmed in all individuals and were found to be anatomically similar. No other congenital malformations were present in these individuals. The genealogy was identified in 1972, when ASD recurred in two generations, and it was concluded that the mechanism of transmission was autosomal recessive. The fifth individual, identified 21 years later, and having an anomaly identical to that of the others, was the child of a couple who had no consaguinity and whose mother was a member of the previously studied genealogy. Considering the absence of phenotype in the parents and the rarity of the ASD gene in the general population, the occurrence of the uniparental disomy for this family nucleus, and the same autosomal recessive mechanism of transmission by this affected individual is possible. This study reports the familial occurrence of ASD by genetic mechanisms of transmission, emphasizing the necessity for genetic-clinical studies in members of the familial nucleus in order to detect new carriers, who usually are asymptomatic, thereby allowing for early and adequate treatment of individuals who may be affected.
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