Jervell and Lange-Nielsen syndrome
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).
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; cardo-cardiac 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.
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.
Although it is the third most common type of auto-somal 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.
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.
All individuals who have been diagnosed with JLNS must avoid reductions in blood potassium levels, such as those that occur with the use of diuretics (drugs that reduce fluids in the body). People with JLNS must also avoid a very long list of drugs and medications that can increase the QT interval or otherwise exacerbate the syndrome.
People with JLNS usually are advised to refrain from competitive sports and to practice a "buddy system" during moderate exercise. Family members are advised to learn cardiopulmonary resuscitation (CPR) in case of cardiac arrest.
Cochlear implants may improve the hearing of people with JLNS. The cardiac abnormalities of JLNS usually can be controlled with beta-blockers. However, without treatment, there is a high incidence of sudden death due to cardiac events.
Family members of a JLNS individual should be screened with ECGs/EKGs for a prolonged QT interval, since they are at risk of having LQTS. Genetic counseling is recommended for people with JLNS, since their children will inherit a gene causing LQTS.
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Deafness Research Foundation. 575 Fifth Ave., 11th Floor, New York, NY 10017. (800) 535-3323. email@example.com.
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Margaret Alic, PhD