Recurrent left atrial myxomas in Carney complex: a genetic cause of multiple strokes that can be prevented
George Briassoulis1, Vladimir Kuburovic, Paraskevi Xekouki
1Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Background:
Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical, and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described. The regulatory subunit (R1A) of the protein kinase gene (PRKAR1A) is mutated in >60% of patients with Carney complex.
Methods:
We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere; a total of 7 patients with 16 recurrent atrial myxomas and >14 episodes of strokes were identified.
Results:
Neurologic deficits were reported; in 1 patient, an aneurysm developed at the site of a previous stroke. All patients were females, were also diagnosed with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, and c.177+1G>A) were located in exons 3 to 5 and introns 2 to 3, and all led to a non-sense PRKAR1A mRNA.
Conclusions:
Female patients with Carney complex appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes.
Insights
Carney complex patients, particularly females, face high risks of recurrent atrial myxomas leading to strokes. Early diagnosis of Carney complex is crucial for preventing strokes and managing atrial myxomas.
Area of Science:
- Cardiology
- Neurology
- Genetics
Background:
- Carney complex-associated intracardiac myxomas cause significant cardiovascular morbidity and mortality.
- Strokes and atrial myxomas in Carney complex lack comprehensive genetic and clinical descriptions.
- PRKAR1A gene mutations are found in over 60% of Carney complex patients.
Observation:
- A cohort of 7 patients with recurrent atrial myxomas and multiple strokes was identified.
- All studied patients were female, diagnosed with Cushing syndrome, and exhibited other Carney complex manifestations.
- PRKAR1A mutations were identified in 71% of patients, predominantly in exons 3-5 and introns 2-3, leading to non-sense mRNA.
Findings:
- Female patients with Carney complex are prone to recurrent atrial myxomas and subsequent strokes.
- Neurologic deficits and aneurysms were observed in stroke patients.
- No significant risk factors were identified beyond gender, though overweight and hypertension trends were noted.
Implications:
- Early identification of female Carney complex patients is vital for timely atrial myxoma diagnosis.
- Proactive management can prevent strokes in high-risk individuals.
- Understanding PRKAR1A mutations aids in risk stratification and targeted therapies.
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:29Hemorrhagic Stroke ll: Pathophysiology
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:25Cardiomyopathy I: Introduction and Classification
01:22Mitral Stenosis I: Introduction
01:23Mitral Stenosis II: Clinical features and Diagnostic Tests