Jervell and Lange-Nielsen Syn... Health Article

Definition

Jervell and Lange-Nielsen syndrome (JLNS) is a rare inherited disorder characterized by congenital deafness and cardiac arrhythmias (irregularities in the electrical activity of the heart that can lead to cardiac arrest and sudden death).

Description

JLNS results from mutations, or changes, in either one of two genes that encode proteins that combine to form potassium ion channels. One of the potassium channels is important for proper heart function. It is also critical in the functioning of the cochlea of the inner ear. People with JLNS lack this channel and, thus, are born with profound deafness in both ears, as well as with cardiac abnormalities.

JLNS was first described in 1957 by A. Jervell and F. Lange-Nielsen. It is also known by the names cardio-auditory syndrome of Jervell and Lange-Nielsen; cardocardiac syndrome; surdocardiac syndrome; deafness-functional heart disease; and deafness, congenital, and functional heart disease. The cardiac (heart) symptoms of JLNS are very similar to those of long-QT syndrome (LQTS), including a longer-than-normal "QT interval" on an electrocardiogram (ECG or EKG) test. Thus, JLNS is sometimes called QT prolonged with congenital deafness.

Genetic profile

JLNS is caused by mutations in either the KVLQT1 (KCNQ1) gene or the KCNE1 (MinK or IsK) gene. It is an autosomal recessive disorder, which means it occurs only in people with two copies of the mutant gene, one from each parent. The mutations in the two copies do not have to be identical. Someone who inherits one copy of the mutant gene and one copy of the normal gene has LQTS types 1 or 5.

Demographics

Although it is the third most common type of autosomal recessive hearing loss, JLNS is a very rare disorder. Worldwide, there are an estimated two to six cases per one million people. Norway, however, has a much higher incidence of JLNS, estimated at one in 200,000.

Because JLNS requires two copies of the abnormal gene, one from each parent, it most often is found in the offspring of related parents, such as cousins (termed a "consanguineous" marriage). Individuals who carry one copy of the abnormal gene and one normal gene copy will have LQTS, but will have normal hearing or only partial hearing loss. However, a child of two such individuals has a 25% chance of having JLNS. Thus, although JLNS occurs across racial and ethnic groups, it is more common in small isolated groups where marriage between relatives is frequent.

Signs and symptoms

The deafness associated with JLNS usually is apparent in infancy or early childhood. Although the severity of JLNS varies, children with acute JLNS are profoundly deaf in both ears.

Depending on the severity of the disorder, the cardiac symptoms of JLNS may be overlooked. Thus, people with JLNS can be at serious risk for sudden death. In addition to a prolonged QT interval on an ECG/EKG, cardiac arrhythmias, dizziness, periods of unconsciousness (syncopic episodes), and seizures are common symptoms of JLNS. These symptoms most often occur upon awakening, during strenuous physical activity, or during moments of excitement or stress.

Diagnosis

Deaf children, particularly those with a family history of sudden death, syncopic episodes, or LQTS should be screened for JLNS, using an ECG to detect a prolonged QT interval. Genetic testing for JLNS is possible for high-risk individuals.

Individuals with JLNS sometimes have normal or borderline-normal QT intervals on an ECG/EKG. Additional ECGs/EKGs performed during exercise may reveal an abnormal QT interval. ECGs/EKGs of the parents may also reveal a prolonged QT interval.

Treatment and management

Since JLNS can result in sudden death, including sudden infant death syndrome (SIDS), treatment is essential. Beta-blockers are the most common treatment for the ventricular arrhythmia of JLNS. Treatment with these drugs usually continues for life. Beta-blockers such as propranolol are considered to be safe medications. Any side effects from propranolol are usually mild and disappear once the body has adjusted to the drug. However, beta-blockers can interact dangerously with many other medications.

Surgery may reduce cardiac arrhythmias in people with JLNS. A mechanical device called a pacemaker or an automatic implanted cardioverter defibrillator (AICD) may be used to regulate the heartbeat or to detect and correct abnormal heart rhythms. Sometimes a pacemaker or AICD is used in combination with beta-blockers.

In 2000, the first cochlear implant in the inner ear of a child with JLNS was reported. The child gained limited hearing and improved speech.