Unique detection of SCN5A deletion by MLPA in teenager with Brugada Syndrome

  • Dr Lucas Eastaugh, The Royal Children's Hopsital, Australia
  • Mr Dean Phelan, VCGS Pathology/ Murdoch Children's Research Institute, Australia
  • Dr Paul James, The Royal Children's Hopsital, Australia
  • Dr Desiree DuSart, VCGS Pathology/ Murdoch Children's Research Institute, Australia
  • A/Prof Andrew Davis, The Royal Children's Hopsital, Australia

    • Mutations in SCN5A account for approximately 25% of cases of Brugada Syndrome(BS). There are no previous reports of SCN5A deletions in BS detected only by multiplex ligation-dependant probe amplification (MLPA).

    OBJECTIVE
    Demonstration that classic sequencing can miss major deletions in BS and sodium channelopathies.

    METHODS
    A 14 year old boy who presented with atrial flutter had a Brugada type 2 pattern after cardioversion to sinus rhythm. He also had significant sinus node dysfunction. At electrophysiological study a type I pattern appeared under general anaesthesia (Figure). The HV interval was prolonged. Polymorphic VT was induced with triple stimuli. Standard sequencing of SCN5A was performed with no abnormalities detected. Given classic clinical features and HV prolongation MPLA was performed.

    RESULTS
    MLPA demonstrated a large deletion (c.999-424_1338+81del0). It was predicted that this deletion would result in SCN5A haploinsufficiency.

    CONCLUSIONS
    In patients in whom there is a high index of suspicion for sodium channelopathy and who have normal sequencing for SCN5A, strong consideration should be given to performing MLPA. This method enables demonstration of large deletions that would have otherwise not have been appreciated and can oocur in childhood.