Currently available genetic screening tests for long QT syndrome (LQTS) miss about a third of cases. Researchers at The University of Auckland's Faculty of Medical and Health Sciences have recently made an important discovery that could significantly increase the diagnostic hit rate.
Genetic diagnoses are important in LQTS because they identify the type of LQTS which guides treatment, and because they permit accurate family screening and genetic counselling. Carey-Anne Eddy, the PhD researcher involved in the project, working with Associate Professor Andrew Shelling said, "Current molecular genetic screening programs identify the genetic cause in only about 70 per cent of cases. This new test offers a dramatically improved success."
The Long QT syndrome is a rare yet almost fatal, heart rhythm disorder occurring right from birth and it causes recurrent collapse and sudden death. Its name comes from the elongated Qt interval seen in the electrocardiogram (ECG ) of people with the disease.
"The risk of sudden death from LQTS can be significantly reduced with the correct medication and clinical treatment," says paediatric cardiologist Associate Professor Jon Skinner of Starship Children's Hospital. "However, the type of genetic mutation and gene in which it occurs, directly influences the type of treatment to which each patient will best respond. Knowing the genetic cause of LQTS in a family also allows extended family members to be screened and offered the most suitable life-preserving treatment and, therefore, has extreme clinical value."
As part of a significant research endeavour to prevent sudden cardiac death in young New Zealanders, funded by Cure Kids, the research study analysed the DNA of 26 patients with LQTS identified by the Cardiac Inherited Disease Group who had tested negative for LQTS gene mutations. The investigation, using new technology, revealed three patients (11 per cent), carried mutations responsible for LQTS which the conventional genetic tests could not detect.
The current standard genetic screening tests (called polymerase chain reaction, followed by genomic sequencing) can detect small changes in a person's DNA. However, it can miss big deletions or large rearrangements of DNA. For this reason, the researchers used a recently described genetic screening method which picks up large-scale gene changes, known as multiplex ligation-dependent probe amplification (MLPA). The study identified two large deletions and one large duplication in genes that encode potassium ion channels in the heart. With certain triggers, like exercise or emotional stress, these mutations may cause an otherwise structurally-normal heart to undergo rhythmic changes which may lead to fainting, epileptic-like seizures and even sudden death.
The research represents one of the biggest advances in the field since the discovery of the first three long QT genes over ten years ago, and will change the routine testing of this important disease. It is currently available online and will be published in the September issue of Heart Rhythm.