Long QT Syndrome Type 3 (LQT3)

Mutation in SCN5A (Na+ channel, INa)

Group E

Qaiyim Cheeseborough, Victoria Reyes & Kin Lung Siu

 

Long QT Syndrome Type 3 (LQT3)

- Congenitally inherited (Genetic) or acquired (Drug therapy)

- Cardiovascular disorder prolonged ventricular repolarization.

- Prevalence level 8%

- Clinical phenotype Prolonged QT wave causing extended

repolarization

- Statistics 1 in 10,000 individuals are affected with LQT

syndromes 8% of these individuals diagnosed with LQT3.

Approximately 3,000 to 4,000 individuals in the U.S die as a

consequence of sudden death.

 

Symptoms

- Fainting (Syncope)

- Sudden death

- Cardiac arrest

- Seizures

 

Diagnosis

- Diagnose through the use of the electrocardiograph (EKG). Abnormal T wave (phenotype) readings can result in determining the form of LQT syndrome the patient has. Any QT interval above 440 milliseconds (ms) is considered prolonged.

- Autopsy of LQT3 syndrome can only be diagnosed through observing for abnormal chemical analysis of the SCN5A gene.

Treatments & Their Effectiveness

- Pacemakers and Automatic Defibrillators

- Medication Mexiletine and Lidocaine

 

Risk Factors [6]

- History of syncope

- Duration of episode and QT interval

- Congenital deafness

- Males: More susceptible during childhood.

- Females: During pregnancy. Cardiac events are common

 

Preventive Measures [7]

- Individuals who present the following should consider being tested for LQT3 syndrome: sudden and unexpected lose of consciousness during childhood and teenage years, sudden or unexplained cardiac arrest, unexplained deaths in family or epilepsy in children.

Functional Role of Transmembrane Proteins (SCN5A)

- Caused by a disorder in the Sodium (Na+) ion channel in the

SCN5A gene. There are approximately 29 known mutations that cause the long QT syndrome where most are the consequence of a single nucleotide substitution. SCN5A intercedes in the permeability of excitable membranes as a function of the alpha () channel [6]. Mutation of the SCN5A protein has been associated with the III-IV linker region responsible for the inactivation of the sodium gates. It is believed that the linker region acts a blocking particle that goes into the channel to block the flow of sodium ions. (Linked to chromosome 13)

 

 

 

 

 

 

 

 

 

 

v     Java Simulation of the Cardiac Action Potential Normal Cell vs. Type III Long QT syndrome

 

 

v     PowerPoint Presentation - Background

v     PowerPoint Presentation II Java Stimulation

 

 

Figure 1: ECG reading provided by the Cleveland Clinic Heart Center [4].

 

 

 

 

 

 

 

Helpful Links

References

Late Updated: May 3, 2003.