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Brief Report
December 2016

Discordant Aortic Valve Morphology in Monozygotic TwinsA Clinical Case Series

Author Affiliations
  • 1Center for Comprehensive Cardiovascular Care, Saint Louis University School of Medicine, St Louis, Missouri
  • 2Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 3Editor, JAMA Cardiology
  • 4Mercy Clinic Heart and Vascular, Washington, Missouri
  • 5Department of Pediatrics, Saint Louis University School of Medicine, St Louis, Missouri
JAMA Cardiol. 2016;1(9):1043-1047. doi:10.1001/jamacardio.2016.2522
Key Points

Question  Can genetic testing in monozoygotic twins with discordant aortic valve morphology (ie, bicuspid and tricuspid aortic valves) contribute to our knowledge of the genetic mechanism of bicuspid aortic valve?

Findings  Whole-exome sequencing from one pair of monozygotic twins and targeted gene testing of a second pair of monozygotic twins identified no genetic alterations.

Meaning  In addition to gene inheritance, epigenetic effects, somatic mutations, and environmental factors may play a more important role than previously suspected, which may limit the usefulness of genetic screening in risk stratification.


Importance  Bicuspid aortic valve (BAV) is considered an autosomal dominant condition, which is commonly associated with thoracic aortic aneurysm. Both conditions pose the risk of valvular and aortic complications not only for affected patients but also for genetically related persons as well. The genetic underpinnings of these disease processes, which are in various stages of elucidation, have implications for screening and risk prognostication.

Objective  To analyze genetic differences between 2 pairs of monozygotic twins that had discordant aortic valve morphology, with 1 twin in each pair having a BAV and the other having a trileaflet aortic valve.

Design, Setting, and Participants  Two pairs of twins that were objectively determined to be monozygotic were examined at a tertiary care medical center associated with an academic medical center. Aortic valves that were surgically excised for clinical indications were examined for morphology. Whole-exome sequencing was performed for the twin pair that had discordance of aortic valve and aortic aneurysm. In the second pair, targeted gene sequencing of 25 genes known to be associated with BAV and/or thoracic aortic aneurysm was performed. In each pair, the twin with a BAV underwent surgical aortic valve replacement for clinical indications.

Main Outcomes and Measures  Genetic coding variations between monozygotic twins using whole-exome sequencing and targeted gene sequencing.

Results  This case series included 2 pairs of male monozygotic twins; one pair was aged 51 years and the other aged 59 years. Genetic sequencing methods identified no pathogenic sequence changes between the twins in each pair.

Conclusions and Relevance  Our findings challenge the traditional view of BAV as a condition with an entirely autosomal dominant inheritance pattern and emphasize the variability of penetrance of both BAV and thoracic aortic aneurysm as well as the variability of the association of the 2 conditions. Continued work to elucidate the genetic basis may lead to the refinement of risk stratification for affected patients and relatives.