Long QT syndrome type 3 (LQT3) is a hereditary disorder of myocardial repolarization characterized by abnormal prolongation of the QT interval on the electrocardiogram. This form of the syndrome is caused by mutations in the SCN5A gene encoding the alpha subunit of the cardiac sodium channel. The disease is particularly dangerous due to the high risk of developing polymorphic ventricular tachycardia of the "pirouette" type and sudden cardiac death, especially at a young age. The pathophysiological mechanism of LQT3 is associated with delayed closure of sodium channels, which leads to an increase in the inward sodium current during the repolarization phase and, as a result, to an extension of the action potential of cardiomyocytes.
History of the disease and interesting historical facts
The first description of long QT syndrome was made by Jervell and Lange-Nielsen in 1957 when studying cases of sudden death in children with congenital deafness. However, the specific subtype LQT3 was identified much later - in 1995 by a group of researchers led by Dr. Mark Keating. Interestingly, many historical cases of sudden death in young athletes were probably associated with this syndrome. According to the study by Wang et al. (1995), about 8-10% of all cases of sudden cardiac death in young people can be associated with mutations in the SCN5A gene.
Epidemiology
According to a 2020 meta-analysis, the prevalence of LQT3 is approximately 1 in 2,500-3,000 newborns. It is the third most common form of congenital long QT syndrome after LQT1 and LQT2. It is important to note the following statistics:
- Approximately 7-10% of all cases of congenital long QT syndrome are LQT3
- The penetrance of mutations is approximately 60-70%
- Sudden cardiac death most often occurs during sleep or rest (unlike other types of LQTS)
According to the European Heart Journal (2019), the average age of first clinical manifestation is 12-14 years.
Genetic predisposition to this disease
The main genetic defect in LQT3 is mutations in the SCN5A gene, located on chromosome 3p21.
“More than 100 different mutations in the SCN5A gene have been described in LQT3, most of which result in delayed sodium channel inactivation” — Circulation Research, 2018
The main types of mutations include:
- Missense mutations (approximately 70% cases)
- Nonsense mutations (15%)
- Splicing mutations (10%)
- Deletions/insertions (5%)
Risk factors for the development of this disease
The main risk factors include:
- Physical: bradycardia, hypothermia, physical exertion
- Chemical: taking certain antiarrhythmic drugs (eg, quinidine), antibiotics (erythromycin), antipsychotics
- Endocrine: hypokalemia, hypomagnesemia
- Emotional: stressful situations
Combinations of these factors are especially dangerous, which can significantly increase the risk of arrhythmic events.
Diagnosis of this disease
The main diagnostic criteria include:
- Prolongation of QTc interval >480 ms
- Characteristic ST-T changes on ECG
- Family history of sudden cardiac death
For laboratory diagnostics the following are used:
- Genetic testing for SCN5A mutations
- Blood electrolyte profile
- Hormonal studies
Radiological methods include cardiac MRI to exclude structural changes. Differential diagnosis includes other forms of LQTS, electrolyte disturbances, and drug effects.
Treatment
The general therapeutic strategy includes:
- Pharmacological therapy
- Implantation of a cardioverter-defibrillator (ICD)
- Lifestyle modification
Surgical treatment is limited to ICD implantation. Non-drug correction methods such as sympathectomy are also used.
List of drugs used to treat this disease
Main groups of drugs:
- β-blockers (propranolol, nadolol)
- Mexiletine
- Flecainide
- Potassium supplements
It is important to note that the effectiveness of different drugs may vary depending on the specific mutation.
Disease monitoring
Monitoring includes regular implementation of:
- ECG every 6 months
- Genetic counseling
- Checking the operation of the ICD (if available)
The prognosis improves significantly with adequate therapy, but the risk of complications remains throughout life. Possible complications include recurrence of ventricular arrhythmia and psychoemotional disorders.
Age-related features of the disease
In childhood, the disease often manifests itself more severely. In adult patients, the symptoms may be less pronounced, but the risk of complications remains high. Specific features:
- Sudden infant death syndrome (SIDS) may occur in newborns
- In adolescence - increased sensitivity to stress
- In adults, association with nocturnal arrhythmic episodes
Questions and Answers
- How often should I have LQT3 screenings? An annual examination with an ECG and consultation with a cardiologist is recommended.
- Is it possible to play sports with this disease? Intense physical activity, especially swimming and team sports, is not recommended.
- How does pregnancy affect the course of the disease? Requires careful monitoring, as the severity of the disease may change due to hormonal changes.
Advice from Dr. Oleg Korzhikov
Based on many years of experience working with patients with LQT3, I would like to point out several important points:
- Patients often ask about the possibility of driving a car. Provided the patient is in a stable condition and has an ICD, driving is allowed, but with restrictions.
- Regarding nutrition: it is important to maintain normal levels of potassium and magnesium, so I recommend regularly eating bananas, avocados, and spinach.
- When asking questions about family planning, it is important to remember the 50% risk of passing on the mutation to offspring, so a consultation with a geneticist is essential.
- As for professional activities, you should avoid jobs that involve stress and responsibility for human lives.
