Posthumous diagnosis of long QT syndrome from the neonatal screening card

  • A/Prof Jonathan Skinner, Starship Childrens Hospital, Auckland, New Zealand
  • Ms Jackie Crawford, Starship Childrens Hospital, Auckland, New Zealand
  • Ms Anne Vaughan, Lap Plus, Auckland., New Zealand
  • Ms Carey-Anne Eddy, University of Auckland, New Zealand
  • Prof Mark Rees, University of Wales, United Kingdom
  • Prof Donald Love, Lap Plus, Auckland., New Zealand
  • A/Prof Andrew Shelling, University of Auckland, New Zealand

    • Background
    Neonatal screening (Guthrie) cards provide a potential source of DNA, but their use in diagnosing inherited cardiac conditions following sudden death has not been assessed.
    Aims
    We report a consecutive series of posthumous genetic tests for long QT syndrome using the Guthrie card.
    Methods
    No post-mortem tissue suitable for DNA extraction was available from 23 families who approached our cardiac genetic clinic seeking a cause of death of their relative 2-14 years after the death. Deaths occurred at <1 year in 3, 1-18 yrs in 15, and 19-35yrs in 4. Informed consent from the next of kin was obtained. DNA was extracted and amplicons corresponding to the coding regions of the long QT (LQT) genes 1, 2, 3, 5, and 6 were subjected to DHPLC screening and/or direct sequencing.
    Results
    Adequate DNA was extracted in every case. A full diagnostic screen was performed in 19 cases. Of these, variants were detected in four (21%) cases: one mutation was detected in the KCNQ1 gene in a 12 yr old boy; two mutations were found in the KCNH2 gene in 20 month and 27 year old females respectively; and a novel variant was found in the SCN5A gene in a three day old infant. Point mutation tests for familial mutations were performed on four cards with a positive result in all four.
    Conclusions
    Guthrie cards, up to 23 years old, provide a valuable and reliable source of DNA for the posthumous diagnosis of long QT syndrome.