What is Jervell and Lange-Nielsen syndrome?
Jervell and Lange-Nielsen syndrome is a condition that causes profound hearing loss from birth and a disruption of the heart’s normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. Beginning in early childhood, the irregular heartbeats increase the risk of fainting (syncope) and sudden death.
How common is Jervell and Lange-Nielsen syndrome?
Jervell and Lange-Nielsen syndrome is uncommon. It affects an estimated 1.6 to 6 per 1 million people worldwide. This condition has a higher prevalence in Denmark, where it affects at least 1 in 200,000 people.
What genes are related to Jervell and Lange-Nielsen syndrome?
Mutations in the KCNE1 and KCNQ1 genes cause Jervell and Lange-Nielsen syndrome.
The KCNE1 and KCNQ1 genes provide instructions for making proteins that work together to form a channel across cell membranes. These channels transport positively charged potassium atoms (ions) out of cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of inner ear structures and cardiac muscle.
About 90 percent of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in the KCNQ1 gene; KCNE1 mutations are responsible for the remaining 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 hearing loss and an irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.
How do people inherit Jervell and Lange-Nielsen syndrome?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of a child with an autosomal recessive disorder are not affected, but are carriers of one copy of the mutated gene. Some carriers of a KCNQ1 or KCNE1 mutation have signs and symptoms affecting the heart, but their hearing is usually normal.
How does Jervell and Lange-Nielsen syndrome affect the heart?
Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in fainting (syncope) or sudden death.
Are there any symptoms?
The classic presentation of JLNS is a deaf child who experiences fainting episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years.
The diagnosis of JLNS is established in a child with congenital sensorineural deafness, long QT interval, and presence of two disease-causing mutations in either KCNQ1 or KCNE1, the only two genes known to be associated with JLNS. Such molecular genetic testing is clinically available.
What is the treatment for Jervell and Lange-Nielsen syndrome?
- cochlear implantation to treat hearing loss
- beta-adrenergic blockers for long QT interval
- implantable cardioverter defibrillators for those with a history of cardiac arrest and/or failure to respond to other treatments.
Source: Genetics Home Reference and Gene Reviews