Discordant aortic valve morphology in monozygotic twins: A clinical case series

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.