| Jervell and Lange-Nielsen syndrome | |
|---|---|
| Other names | Long QT interval-deafness syndrome[1] |
 | |
| The features of Jervell and Lange-Nielsen syndrome include a prolonged QT interval and sensorineural deafness | |
| Specialty | Cardiology |
| Symptoms | Blackouts,seizures,sensorineural deafness |
| Complications | Sudden death |
| Usual onset | Congenital |
| Causes | Genetic |
| Differential diagnosis | Other forms ofLong QT syndrome |
| Treatment | Beta blockers,implantable cardioverter defibrillator |
Jervell and Lange-Nielsen syndrome (JLNS) is a rare type oflong QT syndrome associated with severe, bilateralsensorineural hearing loss.[2] Those with JLNS are at risk of abnormal heart rhythms calledarrhythmias, which can lead tofainting,seizures, or sudden death. JLNS, like other forms of long QT syndrome, causes thecardiac muscle to take longer than usual to recharge between beats. It is caused by genetic variants responsible for producingion channels that carry transportpotassium out of cells. The condition is usually diagnosed using anelectrocardiogram, butgenetic testing can also be used. Treatment includes lifestyle measures,beta blockers, and implantation of adefibrillator in some cases. It was first described byAnton Jervell andFred Lange-Nielsen in 1957.[3]
Jervell and Lange-Nielsen syndrome causes severesensorineural hearing loss from birth, affecting both ears. Those affected have a prolongedQT interval on anelectrocardiogram and are at risk of abnormal heart rhythms (arrhythmias), which can cause dizziness, blackouts, orseizures.[2] In general, JLNS affects the heart more severely than other forms of long QT syndrome. 90% of those with JLNS experience arrhythmias, with 50% becoming symptomatic by the age of 3.[4] In some cases, these arrhythmias lead to sudden death.[citation needed]
Jervell and Lange-Nielsen syndrome is caused bymutations in theKCNE1 andKCNQ1 genes. The proteins produced by these two genes work together to form apotassium channel that transports positively chargedpotassiumions out ofcells, which is called the slow delayed rectifier potassium current. The movement of potassium ions through these channels is critical for maintaining the normal functions of the inner ear and cardiac muscle.[5] JLNS is anautosomal recessive disorder meaning that two copies of the genetic mutation are required to produce the full syndrome. Mutations in the same genes can produce milderRomano-Ward forms of long QT syndrome if only a single copy of the genetic mutation has been inherited.[citation needed]
About 90% of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in theKCNQ1 gene, leading to Jervell and Lange-Nielsen syndrome type 1 (JLNS1).KCNE1 mutations are responsible for the remaining 10% of cases, causing Jervell and Lange-Nielsen syndrome type 2 (JLNS2). 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 the hearing loss and irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.[5]
| Type | OMIM | Gene | Notes |
|---|---|---|---|
| JLNS1 | 192500 | KCNQ1 | Encodes the α-subunit of the slow delayed rectifier potassium channel KV7.1 carrying the potassium currentIKs.[6] |
| JLNS2 | 176261 | KCNE1 | Encodes MinK, a potassium channel β-subunit.[6] |
The sensorineural hearing loss in Jervell and Lange-Nielsen syndrome is present from birth and can be diagnosed usingaudiometry or physiological tests of hearing.[7] The cardiac features of JLNS can be diagnosed by measuring theQT 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.[8]
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 (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. Genetic testing to identify variants in theKCNQ1 orKCNE1 genes can also be used.[8]
The risk of arrhythmias can be reduced in several ways.Medications that further prolong the QT interval such assotalol should be avoided, as should very strenuous or competitive exercise.[2] Bloodpotassium levels should be kept within the normal range. Potassium supplements may be used at times when potassium is being lost such as when experiencingdiarrhoea orvomiting, but medications that encourage the retention of potassium such asspironolactone oramiloride may also be required.[2][9]Beta blockers such aspropranolol ornadolol reduce the risk of arrhythmias.[9]
Animplantable defibrillator, a small device that monitors the heart rhythm and can automatically deliver anelectric 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.[9] 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.[9]
In those who experience recurrent arrhythmias despite medical therapy, a surgical procedure calledsympathetic denervation can be used to interrupt the nerves that stimulate the heart.[2]
The risk of arrhythmias is higher for those with Jervell and Lange-Nielsen syndrome than other forms of long QT syndrome.[10] 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.[11] However, treatment with beta blockers markedly reduces the risk of death, as does, in selected cases, implantation of a defibrillator.[11]
Jervell and Lange-Nielsen syndrome affects an estimated one in 166,000 to 625,000 children, and is responsible for less than 10% of all cases of long QT syndrome. It has a markedly higher incidence inNorway andSweden at up to one per 200,000.[5]
{{cite web}}: CS1 maint: numeric names: authors list (link){{cite book}}:|work= ignored (help)This article incorporates public domain text fromThe U.S. National Library of Medicine