On this page
Jervell and Lange-Nielsen syndrome
JLNS affects both hearing and heart function, typically presenting in childhood. It is caused by specific genetic changes that disrupt normal heart electrical activity and inner ear function, requiring careful medical management.
Available at Jeen Health
Clinical tests that include this
Overview
Jervell and Lange-Nielsen syndrome (JLNS) is an inherited condition that primarily affects two body systems: the ears and the heart. Individuals with JLNS are born with profound sensorineural hearing loss, meaning there is significant damage to the inner ear or the nerve pathways from the inner ear to the brain [PMID:31720166]. Alongside this, they have a heart rhythm disorder called long QT syndrome, which can cause the heart to beat dangerously fast and irregularly. This combination of hearing loss and heart problems defines JLNS.
The condition is rare, and its impact can vary, but the cardiac involvement can be serious, potentially leading to fainting spells (syncope) or, in severe cases, sudden cardiac arrest. Early diagnosis and careful management are crucial for individuals with JLNS to improve their quality of life and reduce health risks.
Symptoms & clinical features
The main symptoms of Jervell and Lange-Nielsen syndrome are profound sensorineural hearing loss from birth and cardiac issues related to long QT syndrome. The hearing loss is typically present at birth and affects both ears, often detected during newborn hearing screening programmes in the UK.
Heart-related symptoms can include fainting spells, especially during physical exertion, emotional stress, or sudden loud noises. These episodes are caused by irregular heart rhythms (arrhythmias) which can be life-threatening. Some individuals may also experience palpitations (a sensation of a racing or pounding heart) or seizures that are actually a manifestation of cardiac events. Symptoms often begin in early childhood, but their severity can differ between affected individuals [PMID:31720166].
Video: Genetics 101
Affected organs
The primary organs affected by Jervell and Lange-Nielsen syndrome are the inner ears and the heart. In the inner ear, the sensory cells responsible for converting sound vibrations into electrical signals are impaired, leading to profound sensorineural hearing loss. This is why individuals with JLNS often require hearing aids or cochlear implants.
In the heart, the electrical system is disrupted, specifically the channels that control the flow of potassium ions into and out of heart cells. This disruption leads to a prolonged QT interval on an electrocardiogram (ECG), which makes the heart more prone to dangerous arrhythmias. These arrhythmias can reduce the heart's ability to pump blood effectively, causing the symptoms mentioned earlier.
Risks & severity
Jervell and Lange-Nielsen syndrome presents a significant risk of life-threatening cardiac events, such as fainting, cardiac arrest, and sudden death, if not properly managed. The profound hearing loss is generally stable and permanent. The severity of cardiac symptoms can vary; some individuals may have frequent episodes, while others have fewer. The onset of cardiac symptoms is typically in childhood, with the highest risk of events occurring during adolescence and young adulthood.
Regular monitoring and appropriate medical intervention are vital to mitigate these risks. While the condition can be serious, advancements in medical treatments and surveillance have significantly improved the outlook for individuals with JLNS.
Genetic causes
Jervell and Lange-Nielsen syndrome is caused by pathogenic changes (sometimes called mutations) in specific genes, most commonly KCNQ1 and less frequently KCNE1 [PMID:20301389]. These genes provide instructions for making proteins that are crucial components of potassium channels. Potassium channels are specialised pores in cell membranes that control the movement of potassium ions.
In the heart, these channels play a vital role in regulating the heart's electrical activity, helping it to beat in a regular rhythm. In the inner ear, similar potassium channels are essential for the proper function of hair cells, which are responsible for hearing. When there are pathogenic changes in KCNQ1 or KCNE1, these potassium channels do not function correctly, leading to both the long QT syndrome in the heart and the profound hearing loss observed in JLNS [PMID:31720166].
- KCNE1 potassium voltage-gated channel subfamily E regulatory subunit 1
- KCNQ1 potassium voltage-gated channel subfamily Q member 1The KCNQ1 gene provides instructions for making a protein that forms a critical part of voltage-gated potassium channels, which are essential for regulating electrical signals in the heart and inner ear.
Inheritance pattern
Jervell and Lange-Nielsen syndrome is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic gene variant - one from each parent - to develop the condition. People who have only one copy of a pathogenic variant are called carriers. Carriers typically do not show symptoms of JLNS but can pass the variant on to their children.
If both parents are carriers of the same pathogenic variant, there is a 25% chance with each pregnancy that their child will inherit two copies of the variant and develop JLNS. There is a 50% chance the child will be a carrier like the parents, and a 25% chance the child will inherit two unaffected gene copies and not be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Jervell and Lange-Nielsen syndrome is often suspected based on the combination of profound sensorineural hearing loss and cardiac symptoms such as fainting or a family history of sudden unexplained death. An electrocardiogram (ECG) is a key diagnostic tool to identify the characteristic prolonged QT interval. Hearing tests confirm the degree of hearing loss.
Confirmation of JLNS requires genetic testing to identify pathogenic variants in KCNQ1 or KCNE1. In the UK, genetic testing for suspected JLNS falls under the NHS Genomic Medicine Service (GMS) and is typically requested by a clinical genetics service or specialist paediatrician or cardiologist. The relevant NHS R-codes for genetic testing for long QT syndrome, which includes JLNS, would apply. Referrals for genetic testing are usually made following a clinical evaluation.
Management & lifestyle
The management of Jervell and Lange-Nielsen syndrome involves a multidisciplinary approach focusing on both the hearing loss and the cardiac condition. For hearing loss, interventions may include hearing aids or cochlear implants, along with educational support tailored for deaf children. For the cardiac component, treatment typically involves beta-blocker medications to help stabilise heart rhythm and reduce the risk of arrhythmias.
In some cases, individuals may require an implantable cardioverter-defibrillator (ICD) to deliver an electrical shock if a life-threatening arrhythmia occurs. Regular cardiology follow-ups, including ECG monitoring, are essential. Lifestyle adjustments, such as avoiding strenuous exercise and certain medications that can prolong the QT interval, are also recommended. Individuals and families are typically supported by clinical geneticists and genetic counsellors through the NHS GMS pathway.
UK care pathway
In the UK, individuals with suspected Jervell and Lange-Nielsen syndrome would typically be referred to a specialist paediatrician or cardiologist who can then involve clinical genetics services. Diagnosis is confirmed through genetic testing, which is part of the NHS Genomic Medicine Service (GMS). Genetic counsellors provide essential support and information to families regarding inheritance, testing options, and family planning. The condition would be investigated under relevant NHS R-codes for inherited cardiac conditions or inherited hearing loss, as appropriate.
Frequently asked questions
Can Jervell and Lange-Nielsen syndrome be cured?
No, there is currently no cure for Jervell and Lange-Nielsen syndrome as it is a genetic condition. However, symptoms can be effectively managed with treatments such as hearing aids or cochlear implants for hearing loss, and medications or devices like ICDs for the heart condition, significantly improving quality of life and reducing risks.
How does JLNS affect daily life?
JLNS can affect daily life through the challenges of profound hearing loss, requiring communication adaptations. The cardiac component means individuals need to be mindful of physical exertion and stress, and follow medical advice closely to prevent fainting or more serious heart events. Regular medical check-ups are also a routine part of living with JLNS.
Are there any specific activities that should be avoided with JLNS?
Individuals with JLNS are often advised to avoid strenuous physical activities, competitive sports, and sudden loud noises, as these can sometimes trigger dangerous heart rhythms. Certain medications that can prolong the QT interval should also be avoided. Your cardiology team will provide specific guidance tailored to your individual condition.
What support is available for families with JLNS?
Families in the UK can access support through NHS clinical genetics services, cardiology teams, and audiology services. Genetic counsellors can provide information on inheritance and family planning. Additionally, various charities and support groups for inherited cardiac conditions and hearing loss offer resources and community support.
How common is Jervell and Lange-Nielsen syndrome?
Jervell and Lange-Nielsen syndrome is considered a rare condition. The exact prevalence is not well established, but it is one of the less common forms of long QT syndrome and genetic hearing loss.
References
- Pabba K, Chakraborty RK. Jervell and Lange-Nielsen Syndrome. 2023. PMID: 30725985
- Hem E, Gjesdal KT, Tranebjærg L. The history of Jervell and Lange-Nielsen syndrome. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2024. PMID: 39692650
- Adam MP, Bick S, Mirzaa GM. Jervell and Lange-Nielsen Syndrome. 1993. PMID: 20301579
- Bitner-Glindzicz M, Tranebjaerg L. The Jervell and Lange-Nielsen syndrome. Advances in oto-rhino-laryngology. 2000. PMID: 10868213
- Tranebjaerg L, Bathen J, Tyson J. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. American journal of medical genetics. 1999. PMID: 10704188
- Eftekharian A, Mahani MH. Jervell and Lange-Nielsen syndrome in cochlear implanted patients: our experience and a review of literature. International journal of pediatric otorhinolaryngology. 2015. PMID: 26205899
- Cusimano F, Martines E, Rizzo C. The Jervell and Lange-Nielsen syndrome. International journal of pediatric otorhinolaryngology. 1991. PMID: 1917338
- Hedley PL, Jørgensen P, Schlamowitz S. The genetic basis of long QT and short QT syndromes: a mutation update. Human mutation. 2009. PMID: 19862833