What is Jervell and Lange-Nielsen Syndrome?
Jervell and Lange Nielsen syndrome (JLNS) is a rare disease that a person might inherit from their parents, causing two main problems: hearing loss in both ears and a condition called a prolonged QTc interval. This QTc interval is essentially the time it takes for the heart’s lower chambers to prepare for the next beat, and if it is too long (usually more than 500 milliseconds), it can lead to a type of very fast and unusual heart rhythm called Torsades de pointes, which may result in sudden cardiac death. This syndrome is a specific type of a group of conditions known as long QT syndrome (LQTS).
The syndrome was first reported in 1957 by two doctors, Anton Jervell and Fred Lange-Nielsen. They studied four children who were born with hearing loss, and all experienced episodes of fainting (syncope). The doctors found that these children had notably prolonged QT intervals on their heart rhythm tests (EKGs), which appeared to be the main cause of their fainting events, as no other reasons could be identified.
What Causes Jervell and Lange-Nielsen Syndrome?
Jervell and Lange-Nielsen Syndrome (JLNS) is a type of disorder that a person is born with and gets passed down from parents to their children. This usually happens when both parents carry a faulty gene. A majority of these cases are because of missing parts in the KCNQ1(90%) and KCNE1 genes. These genes are responsible for making proteins that are vital for the working of potassium channels in the heart and cochlea (an organ in your ear that helps with hearing and balance).
Risk Factors and Frequency for Jervell and Lange-Nielsen Syndrome
The amount of people affected by this disorder can vary greatly, ranging from 1 to 6 people per 1,000,000. However, it’s important to know that certain regions, like Norway and Sweden, have higher rates of the disorder due to genetic factors, with about 1 in 200,000 people affected. The disorder also seems to be more common in Turkey.
Signs and Symptoms of Jervell and Lange-Nielsen Syndrome
Jervell and Lange-Nielsen syndrome (JLNS) is usually suspected in a child who cannot hear and has fainting spells, often triggered by emotional stress or physical exercise. By the age of three, half of these children have experienced a heart-related incident. Other signs that might point to this condition are a history of anemia due to iron deficiency and higher than normal gastrin levels. However, a physical check-up may not reveal much, other than the hearing loss.
- Hearing impaired child with fainting episodes
- Episodes often caused by emotional or physical stress
- 50% chance of a heart event by the age of three
- History of iron deficiency anemia
- Elevated gastrin levels
- A physical examination that doesn’t show much except for deafness
Testing for Jervell and Lange-Nielsen Syndrome
If your child has been born with hearing loss or have fainted spells, they may be suspected of having a condition known as JLNS. The next step is to check the length of the QTc interval – a measurement on an EKG heart test – to see if it’s longer than 500 milliseconds. The confirmation of JLNS is done by identifying changes in specific genes, either KCNQ1 or KCNE1. Testing for these genes can be done one at a time, as part of a panel of multiple genes, or through comprehensive testing of all your child’s genes.
Once JLNS is confirmed, it’s important to understand how much the conditions has affected your child. This might include a thorough hearing test, a consultation with a genetics specialist, a complete blood count to check for anemia (a condition where the body doesn’t have enough healthy red blood cells), and a thorough family medical history check.
Treatment Options for Jervell and Lange-Nielsen Syndrome
In order to prevent fainting, heart attacks, and sudden death, one common treatment is a type of drug known as a beta-blocker. Certain beta-blockers, such as Propranolol and Nadolol, have been found to be more effective than others in preventing heart-related problems. Nadolol is often the most preferred option.
For patients who have already experienced a heart attack, a device called an implantable cardioverter-defibrillator (ICD) may be implanted in their body. This device can help regulate their heart rhythm and potentially prevent other heart attacks. Other reasons a person might have an ICD implanted are if they are identified to be at high risk of heart attack. This includes having a QTc interval (a measurement related to heartbeat) greater than 550 msec, fainting before the age of 5, and being a man over 20 years old with a specific gene variant known as KCNQ1.
For pediatric patients who are showing symptoms despite taking beta-blockers, some doctors in Norway recommend combining the use of a beta-blocker with an atrial pacemaker. The atrial pacemaker is a device that can help regulate heart rhythm.
If a patient is experiencing hearing loss, a device called a cochlear implant can often be used to improve their hearing.
For patients with JLNS who are undergoing any surgical procedure, there are specific considerations related to anesthesia. It is crucial to avoid anything that could cause an irregular heartbeat, including an overactive nervous system response, abnormal body temperature, low blood volume, high carbon dioxide levels, and high airway pressure. Beta-blockers should be quickly accessible, as well as equipment for immediate pacing (regulating heart rhythm) and defibrillation (resetting the heart rhythm) if needed.
What else can Jervell and Lange-Nielsen Syndrome be?
When examining conditions related to long QT syndromes, doctors generally consider a variety of potential causes:
- Romano-Ward syndrome: This is a genetic condition that affects heart rhythm and can lead to a prolonged QT interval, which is a measure of time in the heart’s electrical cycle. It differs from other similar conditions because it doesn’t cause congenital deafness. Diagnosis usually involves an EKG (to check the heart’s electrical activity), assessing the symptoms, and taking into account the family history. The genes most commonly associated with this condition are KCNQ1, KCNH2, and SCN5A.
- Timothy syndrome: This is a rare genetic disease associated with abnormal heart rhythm, heart defects, syndactyly (fusion of digits), developmental delays, and autism spectrum disorders. Doctors diagnose this condition based on these clinical features and by identifying defects in the CACNA1C gene, which controls a type of calcium channel. Unfortunately, the outlook for people with this disease is poor, with most patients passing away by the age of 2.5 years.
- Andersen Tawil syndrome: Like Timothy syndrome, this is a rare genetic condition. It typically features episodes of muscle weakness (flaccid paralysis), prolonged QT interval/irregular heart rhythms, and physical abnormalities such as low-set ears, wide-set eyes, small jaw, fifth digit curvature, fused digits, short stature, and curvature of the spine (scoliosis). The diagnosis is made based on these characteristics and the identification of a variant in the KCNJ2 gene.
- Acquired QTc interval prolongation: In some cases, prolonged QT interval can be caused by medication (including certain heart, gastrointestinal, infection, and mental health drugs), or by low levels of potassium, calcium, or magnesium in the blood.
- Myocardial problems: Some heart muscle diseases and lack of blood supply to some part of the heart, as well as injuries to the central nervous system, can also cause prolonged QT interval.
What to expect with Jervell and Lange-Nielsen Syndrome
More than half of children with JLNS, if not treated, unfortunately pass away before reaching 15 years old. The prognosis or disease outcome often is determined by the specific gene that is mutated, the gender of the patient, and their base QTc level—a term referring to a specific measurement on a heart’s electrical cycle on an EKG, or electrocardiogram. Specifically, mutations in KCNE1 genes may potentially result in a gentler disease course.
The risk of adverse outcomes is lower in females whose QTc falls below 550 msec. An important study by Goldenberg et al., which focused on high-risk Long QT syndrome patients, found that an implanted cardioverter-defibrillator, a device to treat life-threatening heart rhythm problems, helps protect against JLNS related deaths.
Starting beta-blocker therapy, type of medication that reduces blood pressure, early in the disease can also be highly beneficial. Initial use of this medication is linked to fewer heart-related events and an improved chance of survival.
Possible Complications When Diagnosed with Jervell and Lange-Nielsen Syndrome
If a disease is not treated, it can result in some serious complications. These can include fainting (syncope), heart attack (cardiac arrest), and even unexpected death.
- Fainting (syncope)
- Heart attack (cardiac arrest)
- Unexpected death
Preventing Jervell and Lange-Nielsen Syndrome
Jervell and Lange Nielsen Syndrome (JLNS) is a rare medical condition passed down through families that affects the heart’s ability to conduct electricity and the ears. It often begins to show symptoms in early childhood, which can include passing out due to strong emotions or intense physical activity, like exercise, and hearing loss. Treatment for JLNS aims to rectify the hearing loss and prevent future fainting episodes or potentially even more serious conditions like a stoppage of the heart.
Medical professionals often use a device called a cochlear implant to correct hearing loss. This device works by stimulating the nerve in the brain that enables us to hear. Issues with the heart are usually treated with a type of medicine known as beta-blockers, which help to lower the electrical activity in the heart to maintain a normal rhythm and prevent fainting.
If the beta-blockers do not work or if the patient has additional risks, doctors will typically suggest placing a device called an implantable automatic cardioverter-defibrillator. This device monitors the heart rhythm, and if it detects an irregular rhythm, it sends an electrical shock to the heart to restore the normal rhythm and prevent fainting spells.
Regular appointments with the child’s doctors, including their general pediatrician or primary care physician and their heart specialist, are fundamental in avoiding potential complications. It’s also recommended to conduct genetic tests for the patient and their family members to better understand the condition.
