Late Onset Cardiac Presentation of PRKAG2-Mutation Related Disease
Document Type
Article
Abstract
Background
PRKAG2 syndrome (PS), a rare, autosomal-dominant disease caused by mutation in the γ2 subunit of 5’-AMP activated protein kinase is characterized by ventricular pre-excitation, supraventricular tachyarrhythmias (SVT), chronotropic incompetence and hypertrophic cardiomyopathy (HCM). Mean age of symptomatic presentation is <30 years. We present a case of PS-related mutation with late onset of symptoms.
Case
A 69-year-old woman with non-obstructive HCM was referred to HCM Clinic. At age 58 she was diagnosed with an accessory atrioventricular pathway, which was successfully ablated. At age 63 sinus bradycardia associated with lightheadedness and exercise intolerance was noted. During subsequent years, she had increased burden of SVT and was diagnosed with sick sinus syndrome and chronotropic incompetence. Electrical cardioversion, atrial fibrillation ablation and eventually a dual chamber permanent pacemaker were needed for adequate control of rhythm and symptoms. Her family history was significant for a brother, who had an implantable cardioverter-defibrillator and died suddenly in his 50s, as well as another brother with a history of SVT.
Decision-making
Transthoracic echocardiogram had shown severe asymmetric hypertrophy of the septal wall (18 mm), with preserved left ventricular function and no left ventricular outflow tract or mid-cavitary obstruction. Asymmetric hypertrophy had been confirmed by cardiac MRI that also showed patchy late gadolinium enhancing lesions in basal to mid anteroseptal wall and subendocardial scarring of the distal inferoapical wall. Patient underwent genetic testing that first reported 2 variants of uncertain significance in PS and CACNA1C genes. Subsequently, the mutation in PS gene [c. 1004T>C (p.Met335Thr)] was reclassified as likely pathogenic. This placed our patient in the category of hypertrophic cardiomyopathy within the context of metabolic disease.
Conclusion
PS mutation related diseases are rare, and symptoms are usually manifested early. Although our patient had multiple cardiac manifestations associated with the disease, they all expressed themselves only in the 5th and 6th decades of her life.
First Page
2534
DOI
10.1016/S0735-1097(23)02978-9
Publication Date
3-7-2023
Recommended Citation
Gasimli-Gamache L, Shirani J. LATE ONSET CARDIAC PRESENTATION OF PRKAG2-MUTATION RELATED DISEASE. Journal of the American College of Cardiology. 2023 Mar 7;81(8_Supplement):2534-.