Carvajal Syndrome - A Variant Of Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

<h3>Introduction</h3> Mutation in the desmoplakin gene is a well-known cause of cardiac arrhythmogenic right ventricular cardiomyopathy (ARVC). However, this protein is also involved in desmosmonal adhesion to intermediate filaments of the cytoskeleton of skin, thus can present with dermatological manifestations. In Carvajal syndrome, a variant mutation in the desmoplakin gene can present with nonischemic cardiomyopathy with left ventricular (LV) involvement. <h3>Case</h3> 42-year-old African American male with history of heart failure of unclear etiology with an ejection fraction of 23% despite optimal medical therapy, LV thrombus with resolution who presented for work-up of his cardiomyopathy. He denied any prior history of alcohol use, smoking, illicit drug use. His family history illustrated premature CAD in his father with history of cardiac bypass surgery and his uncle died suddenly from an unknown cause. He was compliant on his heart medication including carvedilol, sacubitril-valsartan, spironolactone, digoxin, furosemide and apixaban. A recent left heart catherization showed normal coronaries. Non-ischemic work up revealed unremarkable TSH, HIV, iron studies, and urine drug screen. A cardiac MRI showed reduced biventricular systolic function with LVEF 24%, RVEF 41% and patchy areas of subepicardial and mesocardial delayed enhancement in the LV free wall and septum. Because of his family history of unexplained death in his uncle, a genetic testing was performed and showed a Pathogenic variant, c. 1582C>T (p.Gln528*) in the desmoplakin protein, concerning for a LV variant of arrhythmogenic right ventricular cardiomyopathy. The patient did not report any skin rashes, but did reported history of photosensitivity. A dual chamber implantable cardioverter defibrillator placed. One year later, the patient had episode of VT/VF requiring ICD shock and started on sotalol. Two years later, he is currently doing well with NYHA II symptoms. <h3>Conclusion</h3> Our case illustrates that desmoplakin gene mutation can have different variants. Mutation in desmoplakin gene has traditionally been associated with ARVC. In Carvajal syndrome LV involvement is predominant with fibrotic changes but without fatty involvement. Additionally, patients with Carvajal syndrome may have woolly hair and skin rashes such as striate palmoplantar keratoderma in childhood. Early detection is key as there is risk for sudden cardiac death in these patients.