Molecular Diagnosis of Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 138

genetic test for cardiac channelopathies and cardiomyopathies that can guide the
physician in determining the best treatment options for those who are genetically
predisposed to potentially fatal cardiac arrhythmias caused by long QT syndrome
and related cardiac ion channel diseases. The test examines five cardiac ion channel
genes for a mutation that is likely to cause long QT syndrome. If a genetic mutation
is detected, its type and location can assist the physician in making treatment selec-
tions that could include life-style modification, prescription or avoidance of spe-
cific classes of drugs or the implantation of a defibrillator. A patient's family
members also benefit from the test because it can identify if they inherited the same
mutation as the initially symptomatic patient and may be at risk of a potentially
fatal arrhythmia. These relatives often have ambiguous findings on an ECG, while
the results of the FAMILION ™ test can answer whether or not they carry the famil-
ial mutation.
Familial Atrial Fibrillation
Familial atrial fibrillation, the most common sustained cardiac rhythm disturbance,
affects more than 2 million people in the USA, with an overall prevalence of 0.89%.
The prevalence of this disease rises to 5.9% in individuals over the age of 65, and it
accounts for one third of all strokes in these patients. The clinical manifestations of
familial atrial fibrillation range from palpitations to heart failure. The molecular
basis of this condition is unknown, and physicians typically resort to palliative
therapy in an effort to control ventricular rate and prevent systemic emboli.
A genetic locus for familial atrial fibrillation has been identified at 10q22-q24
by the time - and cost-effective method of pooling DNA of affected and unaffected
family members. Researchers speculate, however, that the basis for familial atrial
fibrillation lies in abnormal atrial triggering because the genes that encode adren-
ergic receptors are located at the mutation site on chromosome 10q. Small molecu-
lar defects in DNA can change the electrophysiological properties of the atria; these
alterations may, in turn, create a substrate for chronic atrial fibrillation.
Idiopathic Ventricular Fibrillation
Ventricular fibrillation is the cause of more than 300,000 sudden deaths each year
in the USA. In about 12% of the cases, there is no demonstrable cardiac or non-
cardiac cause and these cases are classified as idiopathic ventricular fibrillation.
A group of these patients present with characteristic electrocardiographic
changes; this category is also called Brugada Syndrome. Mutations in the sodium
channel gene SCN5A contribute to the risk of developing idiopathic ventricular
fibrillation.