Abstract

Jervell and Lange-Nielsen syndrome (JLNS) is a type of long QT syndrome associated with severe, bilateral sensorineural hearing loss. Long QT syndrome causes the cardiac muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats, called arrhythmias, can lead to fainting, seizures, or sudden death. It was first described by Anton Jervell and Fred Lange-Nielsen in 1957.

Genetic

This condition is an autosomal recessive disorder that affects an estimated one in 166,000 to 625,000 children, and is responsible for less than 10% of all cases of long QT syndrome. It has a markedly higher incidence in Norway and Sweden, up to one per 200,000. Mutations in the "KCNE1" and "KCNQ1" genes cause Jervell and Lange-Nielsen syndrome. The proteins produced by these two genes work together to form a potassium channel that transports positively charged potassium ions out of cells, which is called the slow delayed rectifier potassium current. The movement of potassium ions through these channels is critical for maintaining the normal functions of the inner ear and cardiac muscle.

About 90% of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in the "KCNQ1" gene. "KCNE1" mutations are responsible for the remaining 10% of cases. Mutations in these genes alter the usual structure and function of potassium channels or prevent the assembly of normal channels. These changes disrupt the flow of potassium ions in the inner ear and in cardiac muscle, leading to the hearing loss and irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.

Patients with Jervell and Lange-Nielsen syndrome are born with a severe to profound sensorineural hearing loss which is stable. They have very poor vestibular (inner ear balance) function, which means they are slow achieving locomotor milestones such as sitting and walking.

Treatment

JLNS patients with "KCNQ1" mutations are particularly prone to pathological lengthening of the QT interval, which predisposes them to episodes of "torsades de pointes" and sudden cardiac death. In this context, if the patient has had syncopal episodes or history of cardiac arrest, an implantable cardiac defibrillator should be used in addition to a beta blocker such as propranolol.