LQT1

Long QT Syndrome Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Overview

LQT1 is the most common subtype of long QT syndrome. It is caused by a mutation on chromosome 11p15.5, which codes for the voltage-gated potassium channel, KvLQT1. The defect in the channel is what leads to the lengthened time of repolarization of the heart, leading to a prolonged QT interval seen on EKG. The severity and type of symptoms in LQT1 will vary based on where exactly the mutation is located, and whether it is a homozygous or heterozygous mutation.

Long QT1 Syndrome

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.

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 tochromosome11p15.5. 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 I_Ks 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 anautosomal 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 I_Ks 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.