LQT1
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Long QT Syndrome Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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LQT1 On the Web |
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American Roentgen Ray Society Images of LQT1 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
LQT1 is the most common subtype of long QT syndrome making up to 55% of all cases of long QT syndrome. It often presents as a cardiac event that occurs after exercise, and especially during underwater exercise such as swimming or diving. Homozygous recessive mutations in the gene for LQT1 appear to cause the Jervell and Lange-Nielsen syndrome which is characterized clinically by LQTS and sensorineural deafness. Romano-Ward syndrome is an autosomal dominant form of LQTS that is not associated with deafness. Events before the age of 10 years old only occur in the LQT1 subtype of LQTS. Patients with LQT1 paradoxically show a prolongation in the QT segment on EKG after an infusion of epinephrine, which is also used to unmask latent carriers. LQT1 patients are most likely to have the greatest positive response to therapy with beta blockers when compared with the other LQTS subtypes. The mutation occurs on the short arm of chromosome 11.
LQT1 Subtype
| Type | OMIM | Mutation | Notes |
| LQT1 | 192500 | alpha subunit of the slow delayed rectifier potassium channel (KvLQT1 or KCNQ1) | The current through the heteromeric channel (KvLQT1 + minK) is known as IKs. These mutations often cause LQT by reducing the amount of repolarizing current that is required to terminate the action potential, leading to an increase in the action potential duration (APD). These mutations tend to be the most common yet least severe. |
Genetics and Pathophysiology
LQT1 is the most common type of long QT syndrome, making up about 40 to 55 percent of all cases. This variant will sometimes come to the attention of the cardiologist following a cardiac event during exercise like swimming. The LQT1 gene is KCNQ1 which has been isolated to chromosome 11p15.5. KCNQ1 codes for the voltage-gated potassium channel KvLQT1 that is highly expressed in the heart. It is believed that the product of the KCNQ1 gene produces an alpha subunit that interacts with other proteins (particularly the minK beta subunit) to create the IKs ion channel, which is responsible for the delayed potassium rectifier current of the cardiac action potential.
Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or an autosomal recessive pattern in the same family. In the autosomal recessive mutation of this gene,homozygous mutations in KVLQT1 leads to severe prolongation of the QT interval (due to near-complete loss of the IKs ion channel), and is associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the Jervell and Lange-Nielsen syndrome.
Most individuals with LQT1 show paradoxical prolongation of the QT interval with infusion of epinephrine. This can also unmark latent carriers of the LQT1 gene.
Many missense mutations of the LQT1 gene have been identified. These are often associated with a high risk percentage of symptomatic carriers and sudden death. Mutations that occur in the transmembrane region in the cells of affected persons, are more likely to lead to symptoms and manifestations such as syncope, aborted cardiac arrest and sudden cardiac death, when compared with mutations that occur in the C-terminal region.
History and Symptoms
- Seizures - due to oxygen deprivation that occurs during arrhythmia.
- Fainting - fainting or syncope is the most common symptom LQTS.
- A prodrome may occur before losing consciousness, which may consist of lightheadedness, heart palpitations, blurred vision or weakness.
- Sudden death - a fatal arrhythmia that is not quickly intervened on, may cause sudden death.
- In LQT1, syncope, prodrome or other events particularly occur in the setting of exercise or underwater activities.
Therapy
- Beta-blockers are the first line treatment in LQTS, even in asymptomatic carriers, as they reduce the incidence of syncope and sudden cardiac death.
- Other medications to control non-malignant arrhythmias.
- Electrolytes should be repleted as neccesary.
- Avoidance of triggers (drugs, supplements, loud noises, exercise).
- LQTs is one of the few diseases where genetic testing can provide important guidance, such as in whom to place an AICD (defibrillator) for the primary prevention of cardiac events. [1]
- Placement of a pacemaker may be indicated.
- Left stellectomy is not a cure, but is a second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and AICD is not appropriate.
- Patients with long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.
Genotype-specific Therapy
Recommendations for therapy that are particularly specific to LQT1 patients are:
- To limit strenuous exercise or emotional stress, as these are common triggers for an event in LQT1 patients
- That the patient be treated with a beta-blocker, as LQT1 patients are highly likely to have a positive response to beta-blockers
- To avoid unsupervised swimming unless the patient has an ICD
References
- ↑ Compton SJ, Lux RL, Ramsey MR, Strelich KR, Sanguinetti MC, Green LS, Keating MT, Mason JW. Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation. 1996 Sep 1;94(5):1018-22. PMID 8790040