What is Timothy Syndrome?

Timothy Syndrome is an inherited arrhythmogenic disorder characterized by a long QT interval in the electrocardiogram and frequent episodes of severe arrhythmias that may lead to sudden death. Congenital cardiac defects may also be present in affected patients, and other clinical manifestations include severe episodes of low levels of blood glucose (hypoglycemia). These may lead to death and a neuropsychiatric disease that causes developmental delays and autism. The disease manifests with arrhythmias at an early age, even in the first days of life.


Why will EU-Rhythmy study Timothy Syndrome?


We were part of the team that discovered the gene for Timothy Syndrome: it codes for a protein called Cav1.2 that forms the channels that allow calcium to enter the cardiac cells and orchestrate the process that leads to the rhythmic contraction of the heart muscle. Over the years we have followed patients with Timothy Syndrome carefully characterizing their clinical manifestations and their prognosis over time. We have also realized that unfortunately little is understood about the mechanisms underpinning lethal arrhythmias in these patients.

What are the aims of our research?

Most of what is known about Timothy Syndrome is based on mice models that incompletely recapitulate the human disease. Current knowledge is therefore unable to modify the prognosis of these patients. In our research we want to develop the first genetically modified large mammal model of the disease to map electrical activity of their hearts and discover the arrhythmogenic mechanisms that cause sudden cardiac death. As a second goal, we intend to develop a gene therapy strategy to prevent the consequences of the genetic defects in these patients and allow their return to a normal life.