Key points

Romano‑Ward syndrome is a rare inherited cardiac disorder within the spectrum of congenital LQTS and is the most frequent form. Prolongation of the QT interval on the 12‑lead ECG reflects abnormal ventricular repolarization. This abnormality increases the risk for ventricular tachyarrhythmias such as torsades de pointes, recurrent syncope, and sudden death.

Warning signs include syncope, which in children can be mistaken for epileptic seizures, and cardiac arrest. Emotional stress and physical exertion are the principal triggers.

The syndrome is inherited in an autosomal-dominant pattern (50% chance of transmission), making family screening necessary. This channelopathy results from mutations in genes encoding ion channels involved in cardiac repolarization. About 80% of genetic abnormalities are found in three major genes, corresponding to the most common subtypes:

• KCNQ1 (LQT Type 1): Mortality is increased in boys aged 5-15 and girls aged 13-20; events are most often related to exertion or emotion.
• KCNH2 (LQT Type 2): Major risk is seen in women after age 12-13 and up to 9 months post-partum; risk is also elevated in boys aged 1-13; frequent triggers are sudden stimuli, eg, auditory.
• SCN5A (LQT Type 3): Excess risk begins in childhood, particularly in boys, persisting into adulthood, and occurring during sleep or rest.

This genotype classification guides both diagnosis and risk stratification.

Prevalence is estimated at between 1 in 2000 and 1 in 2500, but the condition is likely underdiagnosed because many mutation carriers are asymptomatic and remain undiagnosed. The syndrome is a major cause of sudden death in apparently healthy young people and may account for 2%-54% of unexplained deaths before age 35.

Diagnosis and Testing

The diagnosis includes

• ECG: prolonged corrected QT interval (QTc), generally greater than 460 ms in women and 450 ms in men. Measurements may be repeated in supine and standing positions or after exertion.
• Schwartz score: integrates symptoms (syncope), family history, and ECG abnormalities to estimate diagnostic probability
• Genetic testing: confirms the diagnosis, clarifies the subtype, and directs family screening
• Differential diagnosis: excludes other causes of syncope (vasovagal, epilepsy) and other channelopathies, such as catecholaminergic polymorphic ventricular tachycardia

Between 20% and 25% of patients with this syndrome may have a normal QTc.

Several risk factors for sudden death have been identified:

• QTc ≥ 500 ms
• Increased risk in boys during childhood and in women after puberty
• Occurrence of syncope, especially when recurrent, unexplained, or when it occurs during the first year of life
• Family history of sudden death

Prenatal diagnosis is possible when the pathogenic mutation has been identified in the family.

Family Screening

In a family with a known mutation, screening should be performed in all first‑degree relatives beginning at birth. If identified, affected relatives should have cardiology follow‑up with an ECG once a year in adults and twice a year in children.

Effective Management Options

• Beta-blockers, particularly nadolol and propranolol. Sotalol is strictly contraindicated because it prolongs the QT interval.
• Left cardiac sympathetic denervation for recurrent syncope, despite beta-blockers
• An implantable cardioverter‑defibrillator after cardiac arrest or for selected high‑risk patients (very prolonged QTc and recurrent symptoms despite beta-blockers)
• Adjunctive measures: avoidance of QT‑prolonging medications, correction of electrolyte disturbances, and restriction from competitive sports

Management of Romano‑Ward syndrome is organized within the Cardiogen healthcare network, which coordinates expert centers providing genetic diagnosis, systematic family screening, and specialized follow-up.

Patients and their families also receive support from the Association for Hereditary Cardiac Rhythm Disorders.

Several experimental approaches are under investigation for treatment, including gene therapy. Future directions include more precise risk‑stratification tools, eg, genotype‑specific scores and machine‑learning algorithms, to identify patients at highest risk for sudden death and to guide personalized management.

This story has been translated from Univadis France, part of the Medscape Professional Network.