Resolution of arrhythjmia after commencement of teh meki in costello syndrome

Abstract

Background: Costello syndrome is part of the family of so-called 'RAS-opathies' which can present with Congenital heart disease, Cardiomyopathy, and Arrhythmias. Novel agents affecting the RAS-APL pathways represent new targets for intervention. Case Description: Baby E was diagnosed with antenatally with a hypoplastic aortic arch, which was confirmed as borderline on postnatal imaging. Costello syndrome was suspected clinically and confirmed on genetic testing. After successful trial off Prostin, he developed obstructive respiratory failure. And after weaning from respiratory support with steroid support, E was found to have developed hypertrophic obstructive cardiomyopathy. This was initially treated with beta-blockade, however E subsequently developed chaotic atrial and ventricular arrhythmias. Rate but not rhythm control was managed with combination of flecainide and high-dose beta blockade.In this context of likely poor outcome, Baby E was discharged to the community with cardiology, general paediatric and palliative care support.At review, he was trialled on the novel MEK inhibitor Trametinib. Within four weeks, Holter monitor demonstrated complete resolution of ventricular and substantial improvement of atrial arrhythmia (6.1% VE and 22.8% AE pre-treatment, 0% and 0.1% post-treatment). Additionally, progression of his hypertrophy was halted, and obstruction stabilised a moderate. W was able to be weaned from flecainide with no recurrence of arrhythmia. Conclusion: Treatment with Trametinib may offer adjuvant therapy for arrhythmias in the context of hypertrophic cardiomyopathy and RAS-opathy. Although arrhythmias are known to improve with time in certain patients, the prompt clinical resolution with low-dose Trametinib may reduce time to control and improve the haemodynamic status in the context of HOCM. Further study is warranted.