P-38/CO-06 : Pleomorphic manifestations of sodium Channelopathy In a family

posted Jan 26, 2017, 8:27 AM by sourav ghosh

Soumya R Mahapatra1Praloy Chakraborty1, H S Isser1Sudheer Arava2, Kausik Mandal3
(1) Vardhman Mahavir Medical College (VMMC) and Safdarjang Hospital, New Delhi, India (2) All India Institute of Medical Science New Delhi, India, (3) Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India

Introduction: Cardiac Channelopathy affecting sodium channel mutation may have multiple clinical manifestations.
Results: A 50 year old female presented with sustained monomorphic ventricular tachycardia requiring DC cardioversion. Post cardioversion she developed bradycardia with irregular ventricular rate and no visible P wave. Echocardiography showed dilatation of right atrium (RA) and right ventricle (RV). Invasive electrophysiological testing showed presence atrial electrogram but despite highest output pacing, right atrium could not be captured. Son of the proband (30 year, male) presented with history of syncope. Surface ECG revealed absent P wave. Echocardiography showed dilatation of RA and RV. Invasive electrophysiological testing was suggestive of atrial standstill. A histological specimen from the right ventricular endocardium was normal. Sister of proband (38 year female) presented with intermittent atrial fibrillation and incomplete RBBB. 24 hours monitoring showed long sinus pauses. Echocardiography showed dilated RA and RV. Invasive electrophysiological testing showed electrically active right atrium. Son of the proband was subjected to genetic analysis by Next Generation sequencing (NGS) technique, which showed that the individual harbours variation in SCN5A (p.Asp1275Asn) and BRCA1 (p.Ser1503Ter) gene. Mutation analysis study showed that proband and her sister harbour the same variation in SCN5A and BRCA1.
Apart from LQTS3 and Brugada syndrome, SCN5A mutation can cause inherited progressive cardiac conduction defect (PCCD), sick sinus syndrome, atrial fibrillation, dilated cardiomyopathy and atrial standstill. Overlap syndromes of cardiac sodium Channelopathy consisting of multiple rhythm disturbances within one family, as in our case have also been reported. Concurrent role of BRCA1 mutation is not clear. BRCA1 mutation has been reported to be associated with increased cardiac apoptosis. Whether it is implicated with the disease manifestations (direct or as genetic modifier) or it is an incidental polymorphism, requires further research.
Conclusion: We report a family presenting with various arrhythmias associated with SCN5A and BRCA1.