ECG criteria
- Measure QT from the beginning of the QRS complex to the end of the T wave, usually in lead II or V5; evaluate several leads and use the longest reliably measured QT; if the end of T is unclear, apply the tangent method
- Calculate QTc using Bazett's formula (QTc = QT / √RR) at a heart rate close to normal; in tachycardia/bradycardia, additionally evaluate using Fridericia's formula
- With a repeatedly confirmed QTc ≥ 480 ms without secondary causes, the probability of congenital LQTS is high; QTc in Jervell and Lange-Nielsen syndrome is often ≥ 500 ms, but this threshold is not mandatory
- Assess T wave morphology: often broad, notched, or biphasic, especially in the precordial leads
- The U wave is not included in the QT interval; if T and U merge, the end of T is determined by the tangent method or in another suitable lead, with repeat recording if necessary
- Evaluate the rhythm for "R on T" premature ventricular beats and episodes of polymorphic VT / torsades de pointes
- Compare QTc with the clinical context: bilateral congenital deafness in a child dramatically increases the probability of this specific syndrome rather than Romano-Ward syndrome; the definitive diagnosis is confirmed by a biallelic pathogenic variant in KCNQ1/KCNE1
What it looks like on ECG
The basis of diagnosis is a prolonged QT interval. It is measured from the beginning of QRS to the end of the T wave, usually in leads II or V5, evaluating multiple leads and taking the longest reliably measured QT; if the end of T is unclear, the tangent method is used. The corrected QT (QTc) in Jervell and Lange-Nielsen syndrome usually significantly exceeds normal values and is often greater than in Romano-Ward syndrome in carriers of the same gene (KCNQ1), as this is a homozygous or compound heterozygous form with a more severe functional defect of the potassium channel.
The T wave is often altered in shape: broad, low-amplitude, biphasic, or notched, especially in precordial leads V2–V4. The U wave is not included in the QT measurement. If T and U merge, the end of T is determined by the tangent method or in a lead where T and U are better separated; if QT cannot be measured reliably, the result is considered indeterminate and confirmed by a repeat recording.
A frequent finding is sinus bradycardia relative to age. Against the background of a prolonged QT, ventricular premature beats falling on the peak or descending limb of the preceding T wave ("R on T") may be recorded, as well as paroxysms of polymorphic ventricular tachycardia of the torsades de pointes type with characteristic "twisting" of the QRS axis around the isoelectric line.
| Parameter | Typical finding |
|---|---|
| QTc | markedly prolonged, often ≥ 500 ms |
| T wave | broad, biphasic, low-amplitude |
| U wave | may be enlarged, not included in QT |
| Rhythm | sinus bradycardia, risk of torsades de pointes |
Mechanism
The underlying cause is biallelic (homozygous or compound heterozygous) pathogenic variants in the KCNQ1 or KCNE1 genes, which encode subunits of the slow component of the delayed rectifier potassium current ($I_{Ks}$). These same subunits are expressed in the inner ear cells responsible for endolymph secretion — which is why the defect manifests simultaneously in both the heart and the cochlea, causing deafness.
With a severe (biallelic) channel defect, ventricular repolarization slows down more than with heterozygous carriage (Romano-Ward syndrome), which results in a more pronounced QT prolongation and increased dispersion of refractoriness between individual myocardial regions. Prolongation of repolarization promotes early afterdepolarizations and triggered activity; in the presence of repolarization heterogeneity, this can trigger torsades de pointes. The exact contribution of transmural dispersion of repolarization and reentry mechanisms remains debated.
Causes
- Biallelic pathogenic variants of the KCNQ1 gene (most cases)
- Biallelic pathogenic variants of the KCNE1 gene
- Most often, each parent transmits one pathogenic variant of KCNQ1 or KCNE1; parents are usually heterozygous carriers and may have a normal QT or manifestations of autosomal dominant LQTS (Romano-Ward syndrome)
Differential diagnosis
- Romano-Ward syndrome is also congenital long QT, usually autosomal dominant, without characteristic congenital bilateral sensorineural hearing loss; mean QTc values may be shorter, but individual overlap between the syndromes is large
- Acquired QT prolongation (drug-induced, electrolyte-related — hypokalemia, hypomagnesemia, hypocalcemia) — distinguished by medication history and laboratory data, no deafness
- Isolated congenital deafness without cardiac syndrome — requires ECG to rule out concomitant QT prolongation
- Short QT syndrome and Brugada syndrome — different morphology and direction of changes, QT is not prolonged
Clinical significance and management
Jervell and Lange-Nielsen syndrome is considered the most malignant form of congenital long QT — the risk of syncope, torsades de pointes, and sudden cardiac death is higher than in Romano-Ward syndrome, often starting in childhood. Any child with congenital bilateral sensorineural hearing loss should be screened with an ECG and QTc measurement to rule out this syndrome, as detection is possible before the first syncopal episode.
To the physician: confirm QTc prolongation on a series of ECGs without secondary causes, evaluate family history of syncope and sudden death, refer for genetic testing (KCNQ1, KCNE1) and an arrhythmologist consultation. Investigations include Holter monitoring to detect ectopy and episodes of torsades de pointes, and an exercise stress test as indicated by a specialist. Treatment tactics (beta-blockers, ICD implantation as indicated, avoidance of trigger factors and QT-prolonging drugs) are determined by a cardiac arrhythmologist according to clinical guidelines and are not detailed at the prescription level in the reference guide.
Common interpretation errors
- Measuring QT in only one lead without comparing with others — risk of underestimating true duration
- Including the U wave in the QT measurement when T and U merge instead of using the tangent method
- Using only Bazett's formula without correction for pronounced bradycardia or tachycardia
- Attributing QT prolongation solely to electrolyte disturbances without considering family history and the presence of deafness
- Ignoring mild QT prolongation in the parents of a child with deafness — they may be heterozygous carriers
- Missing the diagnosis due to the absence of overt symptoms prior to the first syncope
1. What type of inheritance is characteristic of Jervell and Lange-Nielsen syndrome?
The syndrome develops due to biallelic (homozygous or compound heterozygous) variants in the KCNQ1 or KCNE1 genes, meaning it is inherited in an autosomal recessive manner.
2. What extracardiac sign distinguishes Jervell and Lange-Nielsen syndrome from Romano-Ward syndrome?
Both long QT syndromes are associated with a potassium channel defect, but the hallmark sign of Jervell and Lange-Nielsen syndrome is congenital bilateral sensorineural hearing loss due to expression of the same channels in the inner ear.
3. What life-threatening arrhythmia is most characteristic of this syndrome?
Marked QT prolongation promotes early afterdepolarizations and triggered activity, which, in the presence of repolarization heterogeneity, can trigger polymorphic ventricular tachycardia of the torsades de pointes type, capable of progressing to ventricular fibrillation.
Frequently asked questions
How does Jervell and Lange-Nielsen syndrome differ from Romano-Ward syndrome?
Both are congenital long QT syndromes caused by variants in potassium channel genes. Jervell and Lange-Nielsen is inherited in an autosomal recessive manner (requires biallelic variants), is accompanied by congenital bilateral sensorineural hearing loss, and on average results in more pronounced QTc prolongation. Romano-Ward is inherited in an autosomal dominant manner, hearing is unimpaired, although individual QTc overlap between the syndromes is large.
Is this syndrome dangerous?
Yes, this is one of the most severe forms of congenital long QT with a high risk of torsades de pointes, syncope, and sudden cardiac death, often starting in childhood. It requires monitoring by an arrhythmologist and prophylactic treatment.
Should an ECG be performed in all children with congenital deafness?
Yes, it is advisable to perform an ECG and measure QTc in a child with congenital bilateral sensorineural hearing loss so as not to miss this syndrome before the first syncope or life-threatening arrhythmia.
Which gene is most frequently affected in Jervell and Lange-Nielsen syndrome?
Most commonly biallelic pathogenic variants of the KCNQ1 gene, less frequently the KCNE1 gene. Both genes encode components of the IKs potassium current, which is important for both ventricular repolarization and inner ear function.
Can QTc be normal in this syndrome?
Extremely rarely, usually QTc is markedly prolonged, often ≥ 500 ms, although this threshold is not mandatory and phenotypic variability is possible. A slight QT prolongation or its absence is more characteristic of heterozygous carrier parents rather than Jervell and Lange-Nielsen syndrome itself.
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Related terms
More in the «Channelopathies and Cardiomyopathies» section
Sources
- Surawicz B., Knilans T. Chou's Electrocardiography in Clinical Practice, 6th ed.
- Goldberger A.L. Clinical Electrocardiography: A Simplified Approach
- Orlov V.N. Guide to Electrocardiography
- AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram, 2009
Educational material for medical students and physicians. Does not replace clinical guidelines and physical examination; the ECG must always be interpreted in conjunction with the clinical picture.