Novel use of trametinib for treatment of atrial arrhythmia in absence of cardiomyopathy in a patient with Costello syndrome.

We describe a case of novel use of trametinib in treating arrythmia without concomitant cardiomyopathy. Our patient is a two-year-old female born with Costello syndrome due to heterozygous mutations in the HRAS gene c34 G > T p (G12C). Shortly after birth, she was diagnosed with multifocal atrial tachyarrhythmia. Her imaging studies have shown no hypertrophy or CHD. There was poor arrhythmia control despite triple antiarrhythmic therapy. Trametinib, a MEK1 and MEK2 inhibitor, was used in treating her isolated atrial arrythmia, allowing her to wean off other antiarrhythmics. Other case reports have shown trametinib to benefit certain RASopathy patients with lymphatic abnormalities, hypertrophic cardiomyopathy, and concurrent arrhythmias. This case demonstrates effective treatment of isolated arrhythmia without cardiomyopathy, broadening the potential indications for use of trametinib in certain RASopathy patients.