Is Long QT Syndrome A Genetic Disorder?
Congenital long QT syndrome or LQTS is a hereditary cardiovascular condition in which there is prolongation of QT interval on ECG putting the individual at risk for potentially life threatening form of rhythm disorder or arrhythmia. This condition is believed to occur in 1 out of every 2000 people. The primary presenting features of long QT syndrome include episodes of syncope which can ultimately cause a severe cardiac arrest and sudden death.
It is possible to record the electrical signal produced by the ions by an electrocardiograph. This machine makes traces of signals, which is called “wave forms” and whose different parts are represented by the letters P, Q, R, S, and T.
Observing the waveform can determine how long it takes for the electrical signal to activate and deactivate the lower cavities of the heart (the ventricles), which is called the QT interval. A problem in one of the ion channels tends to prolong this interval and this, in turn, can increase the risk of suffering a type of arrhythmia known in French as torsade de pointes (twisting of the tips). When the “tips twist”, the heart cannot pump enough oxygen-rich blood to the rest of the body, especially the brain, and could lead to ventricular fibrillation: a dangerous type of arrhythmia, which causes rapid and uncoordinated contractions of the heart.
All patients with prolonged QT syndrome may experience arrhythmic cardiac disorders, regardless of the value they present in the QTc interval and the existing chromosomal alteration; however, in a small number of families, a particularly malignant evolution has been described, with sudden death in the young members of several generations. The long QT syndrome affects people who seem to be very healthy, especially for children and young adults.
About The Genetic Origin
The genetic origin of long QT syndrome disease was discovered at in the middle period of the ‘90s and the genes responsible for this condition are believed to code for cardiac ion channel subunits or the proteins involved in modulation of ion currents. Mutations in these genes namely KCNQ1, KCNE1, CACNA1c, and SCN5A result in prolongation of the QT interval resulting in Long QT Syndrome.
The most common variant of long QT syndrome disease is the QTL1 which results due to mutations in KCNQ1 gene and approximately 50% of patients are believed to be carriers of these mutations. Due to the specificity of the clinical symptoms of long QT syndrome, typical cases do not present any difficulties in diagnosing this condition for most of the physicians who are familiar with the condition. However, some cases are a lot more complex as there is very little in the form of symptoms making a diagnosis difficult. Such cases require thorough evaluation with multiple electrocardiographic studies along with clinical and family history to make an accurate diagnosis.
Molecular screening is yet another addition for a timely and accurate diagnosis of Long QT Syndrome. The management of the disease in majority of the cases always begins with administration of beta-blockers the patient is not a suitable candidate for this class of medications. If, despite a maximum dose of beta-blockers, the patient presents episodes of syncope, a left cardiac sympathetic denervation should be performed and should be considered a treatment with implantable cardioverter-defibrillator (ICD), taking into account the characteristics of the patient (age, sex, clinical history and genetic subgroup, with specific characteristics depending on the mutation in some cases, as well as the presence of ECG signs -including Holter recordings of 24 hours- indicators of high electrical instability).
In general, for patients diagnosed and treated correctly, the prognosis of long QT syndrome is good. However, there are some serious exceptions for patients with long QT syndrome variants: patients with Timothy syndrome (characterized by marked prolongation of the QT interval, atrioventricular block 2: 1 and syndactyly), patients with Lange-Nielsen syndrome and Jervell carriers of KCNQ1 mutation (severe form of long QT syndrome associated with congenital deafness and a very early onset of cardiac arrhythmias) and patients with QTL3 with atrioventricular block 2: 1 and very early onset of cardiac arrhythmias.
The transmission of long QT syndrome disease is autosomal dominant. It is one of several ways in which a trait or disorder can be transmitted from parents to children.
Long QT syndrome is an autosomal dominant trait meaning that only one copy of the defective gene from either parent is good enough to lead to the development of this condition. Commonly, it is observed that at least one parent of the patient has had Long QT Syndrome.