LQT4
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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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LQT4 On the Web |
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American Roentgen Ray Society Images of LQT4 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [3]
Overview
The LTQ4 subtype of long QT syndrome is caused by a mutation in the genes which code for proteins cause ankyrins. People with this mutation experience sinus bradycardia, junctional escape rhythms, atrial fibrillation, and sudden death after physical or emotional stress. Ankyrins are important proteins that bind to various types of vital cell membrane channels which regulate the concentration of intracellular electrolytes. Abnormalities in the channels as a result of defective ankyrin proteins can lead to dangerous levels of intracellular calcium, and fatal arrhythmias. LQT4 is the only subtype of LQTS that does not involve sudden cardiac death as a part of another genetic disorder called Rett syndrome.
LQT4 Subtype
| Type | OMIM | Mutation | Notes |
| LQT4 | 600919 | anchor protein Ankyrin B | LQT4 is very rare. Ankyrin B anchors the ion channels in the cell. |
Genetics and Pathophysiology
The LQT4 genes are ANK2 and ANKB which are located on chromosome 4q25-27 [1], and code for proteins called ankyrins. They are proteins which affect the function of several important ion channel proteins such as the chloride-bicarbonate anion exchanger, ATPase, calcium release channels, and the voltage gated sodium channel. The proteins physically link the lipid bilayer of the cell membrane to the skeleton of the membrane. A mutation in the LTQ4 genes that code for ankyrins can cause increased intracellular concentrations of calcium, and can therefore cause fatal arrhythmias. People with this mutation experience sinus bradycardia, junctional escape rhythms, atrial fibrillation, and sudden death after physical or emotional stress has also been known to occur.
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 LQT4, events may particularly occur after physical or emotional stress.
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. [2]
- 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.
References
- ↑ Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH; et al. (2003). "Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death". Nature. 421 (6923): 634–9. doi:10.1038/nature01335. PMID 12571597.
- ↑ 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