What Is Jervell and Lange-Nielsen Syndrome?
Jervell and Lange-Nielsen syndrome is a rare genetic disorder characterized by bilateral sensorineural hearing loss (damage to the inner ear causing hearing loss) from birth and irregular heartbeats (arrhythmias). This autosomal recessive disorder is a form of prolonged QTc interval (time taken by the heart muscle to contract and recover) of greater than 500 milliseconds leading to Torsades de pointes (ventricular tachycardia) and sudden cardiac death.
This disorder is a form of inherited long QT syndrome (a heart disorder that causes the heart muscle to take longer than usual to recharge between beats). This activity usually begins in early childhood with irregular heartbeats, increasing the risk of syncope (temporary loss of consciousness) and sudden heart failure causing death.
The disease was first explained by Anton Jervell and Fred Lange-Nielsen in 1957 in a study conducted among four children born with congenital deafness that all suffered from temporary consciousness. There was a marked prolonged QT interval in electrocardiographic studies with no other possible cause for the fainting of the patient.
What Is the Etiology of Jervell and Lange-Nielsen Syndrome?
Jervell and Lange-Nielsen Syndrome is a congenital autosomal recessive disorder. Most cases occur due to deletion mutations in 90 percent of the cases in the KCNQ1 gene (potassium voltage-gated channel subfamily Q member 1), and the KCNE1 gene (potassium voltage-gated channel subfamily E member 1) is responsible for the remaining cases. These genes are responsible for encoding proteins that are critical in maintaining the functions of potassium channels across the cell membranes in the heart and inner ear muscles (cochlea). These potassium channels actively transport positively charged potassium ions out of these cells.
Genetic mutations affect the usual structure and function of these potassium channels. These altered changes cause disruption in the flow of potassium ions in the cochlea and cardiac muscles, leading to permanent hearing loss and irregular arrhythmias that are characteristic of Jervell and Lange-Nielsen syndrome.
What Is the Epidemiology of Jervell and Lange-Nielsen Syndrome?
Jervell and Lange-Nielsen syndrome is a rare and uncommon condition. It affects approximately 1.6 to 6 per 1 million people in the world. This disorder is more prevalent in Denmark, Sweden, Turkey, and Norway, where it usually affects at least one in 200,000 people. Norway and Sweden have a remarkably high prevalence at one in 200,000 due to established genetic traits.
What Is the Inheritance Pattern of Jervell and Lange-Nielsen Syndrome?
This disorder is inherited in an autosomal recessive pattern (both copies of the gene in each cell have genetic mutations). Usually, the parents of an affected child suffering from an autosomal recessive disorder are not affected. They act as carriers of one copy of the mutated gene.
What Are the Other Synonyms of Jervell and Lange-Nielsen Syndrome?
The disease is also known by the following names:
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Autosomal recessive long QT syndrome (LQTS).
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Cardio-auditory-syncope syndrome.
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Cardio auditory syndrome of Jervell and Lange-Nielsen.
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Deafness, congenital, and functional heart disease.
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Jervell-Lange Nielsen syndrome.
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Prolonged QT interval in ECG (echocardiography) sudden death.
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Surdo-cardiac syndrome.
What Are the Signs and Symptoms of Jervell and Lange-Nielsen Syndrome?
The following clinical features are seen in this syndrome:
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The child has been deaf since birth.
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Episodes of temporary loss of consciousness (syncope) are experienced by the child. These syncopal episodes are aggravated by physical exercise or mood swings.
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Almost fifty percent of patients have cardiac issues by the age of three.
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A history of iron deficiency anemia is also reported in these patients.
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Elevated gastrin levels are also present.
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Other than deafness, all other physical features are not remarkable.
What Are the Diagnostic Methods for Jervell and Lange-Nielsen Syndrome?
Once Jervell and Lange-Nielsen Syndrome in a child suffering from congenital deafness and syncopal episodes are suspected, the second step is to evaluate the QTc interval to check if it is longer than 500 milliseconds.
Identifying the genetic mutations in either the KCNQ1 or KCNE1 usually confirms the diagnosis. Gene testing can be done either as a single-gene test, a multigene panel, or comprehensive genomic testing.
What Is the Treatment of Jervell and Lange-Nielsen Syndrome?
After establishing the diagnosis, the extent of the disease severity should be assessed. Evaluation of the disease severity should include a formal audiology (science dealing with hearing loss) evaluation, geneticist consultation, complete blood count to assess anemia, and complete family history.
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The first line of treatment therapy for preventing syncope, cardiac arrest, and sudden death is a beta-blocker drug. Propranolol and Nadolol have been found to be superior to Metoprolol in preventing cardiac complications. Nadolol is the most preferred drug in the current scenario. In patients with a history of cardiac arrest, an implantable cardioverter-defibrillator (a small device operated by the battery placed in the chest to detect and stop irregular heartbeats or arrhythmias) should be placed.
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A scientist named Fruh et al. from Norway suggests the combined treatment modality of an atrial pacemaker in the heart, and beta-blocker should be followed to treat these patients.
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Cochlear implantation is usually preferred for hearing loss and is usually treated successfully.
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Anesthesia required for any surgical procedure has certain implications for a patient suffering from Jervell and Lange-Nielsen Syndrome. Any trigger to arrhythmia should be carefully avoided.
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Avoid using high airway pressure.
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Beta-blockers should be readily available along with equipment for immediate transcutaneous or transvenous pacing and defibrillation (using an electrical current to return the heart to a normal rhythm in cases of arrhythmias).
What Is the Prognosis of Jervell and Lange-Nielsen Syndrome?
More than fifty percent of untreated children die before fifteen years of age. The prognosis highly depends on the mutated gene, gender, and baseline QTc. Mutations in the KCNE1 genes usually have a more benign disease course. Females are at lower risk with a QTc of less than 550 milliseconds. Beta-blocker drug therapy is advised to start at an early disease state to reduce the risk of cardiac attacks and to improve the mortality rate.
Conclusion
Jervell and Lange-Nielsen syndrome is a hereditary autosomal recessive disorder characterized by profound hearing loss since birth and irregular heartbeats (arrhythmias). Other than deafness, all other physical features are unremarkable. It is important to treat the disease on an urgent basis since the complications of the untreated disease can lead to temporary loss of consciousness, cardiac arrest, and even sudden death.
