Long-QT syndrome and channelopathies — branching viva

Examiner opening (Examiner)

You are the general paediatric registrar in the emergency department. A nine-year-old girl is brought in after collapsing during a school swimming carnival. She was pulled from the pool unconscious, jerked briefly, and recovered fully within two minutes. Her twelve-lead ECG shows a QTc of 520 milliseconds, and her mother mentions she has fainted "all her life." The team is arranging a CT head and an EEG. Talk me through your assessment and management. [1]

Exemplar opening (Candidate)

This child has high-probability long-QT syndrome, and the team is misdirecting the workup toward a neurological cause when this is a cardiac arrhythmia. The QTc of 520 milliseconds is diagnostic of long-QT syndrome regardless of symptoms — a QTc above 500 milliseconds confers high risk of arrhythmic events. The collapse during swimming is the classic trigger for LQT1 (KCNQ1 mutation), and the maternal history of fainting is a family history clue suggesting an inherited arrhythmia syndrome. The seizure-like movements are the cerebral hypoxia of a transient arrhythmia — torsades de pointes that self-terminated — not epilepsy. My immediate plan is to admit her for cardiac monitoring, stop any QT-prolonging medications, check and correct electrolytes (particularly potassium above 4.0), restrict her from swimming and sport, and refer urgently to the inherited cardiac conditions service for genetic testing and definitive management. The CT head and EEG are not the priority. [1] [2]

Branch 1 — the diagnosis and the Schwartz score (Examiner)

How do you formally confirm the diagnosis of long-QT syndrome, and what is the Schwartz score? [1]

Exemplar (Candidate)

The diagnosis integrates the electrocardiogram, the clinical history, and the family history through the Schwartz diagnostic score. The QTc of 520 milliseconds scores three points on its own — the score awards one point for QTc between 450 and 480, two for 480 to 500, and three for above 500. The syncopal event triggered by exertion — swimming — scores two points if it was definitely exertional. The family history of fainting, if confirmed as definite LQTS or unexplained sudden death before thirty in an immediate family member, scores at least a half to one point. Her total is well above the high-probability threshold of four, which warrants genetic testing. I should also confirm the QTc by manual measurement from the onset of the QRS to the end of the T wave in lead II or V5, corrected with Bazett's formula, because the automated machine reading is frequently inaccurate in children. [1]

Branch 2 — the three cardinal genotypes (Examiner)

Tell me about the three main genotypes of long-QT syndrome and why the genotype matters. [2]

Exemplar (Candidate)

The three cardinal genotypes are LQT1, LQT2, and LQT3, defined by the affected ion channel. LQT1 is caused by mutations in KCNQ1, which encodes the slow delayed-rectifier potassium channel — the IKs current that is the repolarising reserve during sympathetic stimulation. Without it, the heart cannot shorten its action potential when the rate rises, so events occur during exercise, emotion, and particularly swimming — the diving reflex and adrenergic surge stress the channel maximally. LQT2 is caused by KCNH2 mutations affecting the rapid delayed-rectifier potassium current IKr, and its hallmark trigger is sudden loud noises — alarm clocks, telephones — because the abrupt catecholamine surge stresses the compromised channel. LQT3 is caused by SCN5A mutations that produce a gain of late sodium current, prolonging the plateau phase, and events occur at slow heart rates during sleep or rest. The genotype matters because it guides therapy: beta-blockers are highly effective in LQT1, moderately effective in LQT2, and poorly effective in LQT3 — for LQT3, mexiletine or ranolazine may be used as adjuncts, and the ICD threshold is lower. This child's swimming trigger strongly suggests LQT1. [2] [3]

Branch 3 — management (Examiner)

What is the definitive management for this child? [3] [5]

Exemplar (Candidate)

The four pillars are lifestyle modification, beta-blockade, non-pharmacological adjuncts, and the ICD for the highest-risk patients. Lifestyle modification is universal: she must avoid competitive and exertional sport, she must never take a QT-prolonging medication without checking, and she needs aggressive management of electrolyte disturbance during intercurrent illness. The first-line therapy is a beta-blocker, and I would start nadolol at 0.5 to 2 mg per kilogram per day — it is the preferred agent in children because of its long half-life and tolerability. Beta-blockers reduce events by approximately two-thirds across the LQTS cohort. For a patient who has breakthrough events on maximally tolerated beta-blockers, the next step is left cardiac sympathetic denervation — a thoracoscopic procedure that removes the lower half of the left stellate ganglion and the first thoracic ganglia, reducing cardiac sympathetic input. Schwartz and colleagues showed it reduces events by over ninety per cent, and it is particularly valuable in children because it avoids the complications of an implanted device. The ICD is reserved for the highest-risk patients: survivors of aborted cardiac arrest, those with recurrent syncope despite beta-blockers and LCSD, and very high-risk genotypes. [3] [4]

Branch 4 — the family (Examiner)

What about her mother and her siblings? [6]

Exemplar (Candidate)

Long-QT syndrome is autosomal dominant with incomplete penetrance, so every first-degree relative is at risk. Once a pathogenic mutation is identified in this child — most likely KCNQ1 given the swimming trigger — all first-degree relatives need cascade screening: a twelve-lead ECG with manual QTc and targeted genetic testing for the specific mutation. Her mother's history of "fainting" may well represent undiagnosed LQTS, and her siblings may be asymptomatic but genotype-positive. A relative who tests negative for the family mutation is not at risk and does not need further surveillance; a relative who tests positive needs the same management pathway regardless of symptoms. Genetic counselling is essential for the whole family, because the diagnosis has implications for lifestyle, reproduction, and psychosocial wellbeing. [6] [2]

Branch 5 — CPVT (Examiner)

Now suppose a different child presents with exertional syncope but a normal resting ECG and a structurally normal heart. What are you thinking? [5]

Exemplar (Candidate)

That presentation — exertional syncope, a structurally normal heart, and a normal resting ECG — is catecholaminergic polymorphic ventricular tachycardia until proven otherwise. CPVT is a calcium-handling disorder, most commonly caused by mutations in the cardiac ryanodine receptor RYR2, that causes calcium leak from the sarcoplasmic reticulum during adrenergic stress. The resting ECG is normal because the calcium leak is adrenergine-dependent. The diagnostic test is exercise stress testing, which provokes the characteristic bidirectional or polymorphic ventricular tachycardia at higher heart rates. Management is a beta-blocker — nadolol is first-line — with flecainide as an adjunct for breakthrough ectopy, and LCSD or ICD for recurrent events. The key teaching point is that any child with exertional syncope and a normal resting ECG must have an exercise test before CPVT is excluded — a normal resting ECG is not reassuring in this context. [5] [2]

Branch 6 — the acute torsades (Examiner)

Suppose a child with known LQTS is admitted and develops torsades de pointes on the monitor. How do you manage it acutely? [5]

Exemplar (Candidate)

If the torsades is pulseless, I defibrillate immediately following the paediatric advanced life support protocol. If the child has a pulse, the most effective acute therapy is intravenous magnesium sulphate at 25 to 50 mg per kilogram, up to 2 grams, which suppresses the early afterdepolarisations that drive torsades. I would simultaneously correct any electrolyte abnormalities — particularly potassium and magnesium — and discontinue any QT-prolonging medications. If the torsades is sustained or recurrent, temporary overdrive pacing at 100 to 120 beats per minute shortens the QT interval by reducing the action-potential duration and suppresses the arrhythmia. Isoprenaline can be used to maintain a faster heart rate if the child is bradycardic. Once the rhythm is stable, I would review the background therapy — assess adherence, confirm the genotype, and consider escalation to LCSD or ICD if this was a breakthrough event on beta-blockers. [5]

Examiner wrap-up (Examiner)

Thank you. Summarise the three points you most want the examiner to remember. [1]

Exemplar (Candidate)

First, every child with unexplained syncope, seizure, or sudden death gets a twelve-lead ECG with manual QTc measurement — the single most commonly missed investigation. A QTc above 500 milliseconds is diagnostic of long-QT syndrome. Second, the three cardinal genotypes have specific triggers that guide management: LQT1 (exercise and swimming) responds well to beta-blockers, LQT2 (sudden loud noises) moderately, and LQT3 (sleep and rest) poorly. Third, for breakthrough events on maximally tolerated beta-blockers, left cardiac sympathetic denervation reduces events by over ninety per cent and is the preferred intermediate step in children before an ICD. [1] [4]