Jervell Lange-Nielsen syndrome

Other Names: JLNS1; Deafness, congenital, and functional heart disease; Prolonged QT interval in EKG and sudden death; Cardioauditory syndrome of Jervell and Lange-Nielsen; Surdo-cardiac syndrome; Jervell and Lange-Nielsen syndrome; Long QT interval-deafness 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.

Epidemiology

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, Sweden, and Norway, where it affects at least 1 in 200,000 people.

Types

There are two different types of JLNS type: 1, caused by mutations in the KCNQ1 gene, and type 2, caused by mutations in the KCNE1 gene.

Cause

Jervell and Lange-Nielsen syndrome is caused by mutations in the KCNE1 and KCNQ1 genes. These 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

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 a long QT interval with related heart abnormalities, but their hearing is normal.

Signs and symptoms

Jervell and Lange-Nielsen syndrome causes severe sensorineural hearing loss from birth, affecting both ears. The severity of cardiac symptoms seen in individuals varies from no apparent symptoms to increasing heartbeat (tachycardia), fainting, and cardiac arrest.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Bilateral sensorineural hearing impairment
• Profound sensorineural hearing impairment
• Prolonged QTc interval

30%-79% of people have these symptoms

• Loss of consciousness(Passing out)
• Postexertional malaise
• Syncope(Fainting spell)
• Torsade de pointes

5%-29% of people have these symptoms

• Iron deficiency anemia
• Seizure
• Ventricular fibrillation

Diagnosis

The sensorineural hearing loss in Jervell and Lange-Nielsen syndrome is present from birth and can be diagnosed using audiometry or physiological tests of hearing.

The cardiac features of JLNS can be diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG). The QTc is less than 450 ms in 95% of normal males, and less than 460 ms in 95% of normal females. In those with Jervell and Lange-Nielsen syndrome the QTc is typically greater than 500 ms.

Other factors beyond the QT interval should be taken into account when making a diagnosis, some of which have been incorporated into scoring systems such as the Schwartz score. These factors include a history of characteristic abnormal heart rhythms , unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. Genetic testing to identify variants in the KCNQ1 or KCNE1 genes can also be used.

Treatment

• The treatment of individuals with JLNS focuses on treating hearing loss utilizing devices such as cochlear implants and preventing other symptoms such as fainting and cardiac arrest.
• The risk of arrhythmias can be reduced in several ways. Medications that further prolong the QT interval such as [sotalol]] should be avoided, as should very strenuous or competitive exercise.
• Blood potassium levels should be kept within the normal range. Potassium supplements may be used at times when potassium is being lost such as when experiencing diarrhoea or vomiting, but medications that encourage the retention of potassium such as spironolactone or amiloride may also be required. Beta blockers such as propranolol or nadolol reduce the risk of arrhythmias.
• An implantable defibrillator, a small device that monitors the heart rhythm and can automatically deliver an electric shock to restart the heart, may be used. These devices are recommended for those with JLNS who have experienced a cardiac arrest or a blackout whilst taking beta blockers.
• Due to the higher risk of arrhythmias associated with JLNS than other forms of long QT syndrome, a defibrillator may be considered even in those without any symptoms.

In those who experience recurrent arrhythmias despite medical therapy, a surgical procedure called sympathetic denervation can be used to interrupt the nerves that stimulate the heart.

Prognosis

The risk of arrhythmias is higher for those with Jervell and Lange-Nielsen syndrome than other forms of long QT syndrome. Although this risk is dependent on the underlying genetic defect and degree of QT prolongation, without treatment more than 50% of those affected will die before the age of 15.However, treatment with beta blockers markedly reduces the risk of death, as does, in selected cases, implantation of a defibrillator.

NIH genetic and rare disease info

• NIH info on Jervell Lange-Nielsen syndrome

Jervell Lange-Nielsen syndrome is a rare disease.

Jervell Lange-Nielsen syndrome Resources
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