PO02 A Novel TRPM4 Gene Associated with Long QT Syndrome

Background Genetic testing has significantly advanced the diagnosis of arrhythmias by establishing associations to specific genes. While numerous well-established genes have been implicated in Long QT Syndrome, the dynamic nature of genetic mutations suggests that additional genes may yet be discovered in association with cardiac genetic disorders. A case report from China proposed a potential association between TRPM4 gene with congenital Long QT Syndrome. However, the association of TRPM4 gene with Long QT Syndrome remains largely unexplored. Purpose The aim of this report is to identify the association of transient receptor potential melastatin 4 (TRPM4) gene with the incidence of Long QT Syndrome. Methods We reported a case of a 64-year-old male patient who presented to the emergency department following a near-syncope episode. He reported two prior near-syncope incidents and had initially received a diagnosis of transient ischemic attack. Notably, his father had experienced a similar episode, although no other family members reported related symptoms. Additionally, the patient is managing uncontrolled hypertension and was subsequently referred to a cardiologist to exclude any cardiac-related causes for his symptoms. A blood sample was collected for whole exome sequencing (WES), and bioinformatics tools were employed to analyse the data for inherited diseases. Results An electrocardiogram (ECG) revealed sinus rhythm with a prolonged QT interval measuring 546 ms, while echocardiography results were within normal limits. A 24-hour Holter monitor assessment indicated a corrected QT interval (QTc) of 546 ms, with no documented episodes of near syncope. Genetic testing was conducted, which identified a heterozygous variant of uncertain significance (VUS) in exon 19 of the TRPM4 gene (chr19:49703929C>A, c.2840C>A, p.Ala947Asp). Notably, approximately 97% of known TRPM4 missense variants are classified as VUS, posing significant challenges in diagnosis and clinical management. The patient was started on propranolol to reduce the QT interval. Following treatment, he has not experienced further near-syncope episodes. Subsequent monitoring a month later recorded a reduction in QTc to 515 ms. The patient remains on propranolol but declined the option of an implantable cardiac defibrillator due to financial constraints. Conclusions The TRPM4 gene variant identified in this case has not been established as a genetic cause of Long QT Syndrome. This case may contribute valuable insights into the genetic pathogenesis of Long QT Syndrome associated with TRPM4 gene variants, warranting further investigation.