Romano-Ward Syndrome

Synonyms: autosomal-dominant long QT syndrome, long QT syndrome type 1, LQTS1, RWS, Romano-Ward long QT syndrome, Ward-Romano syndrome

Romano-Ward syndrome is an inherited heart disorder characterised by prolongation of the QT interval, often in association with episodes of ventricular tachyarrhythmia, torsades de pointes, syncope and sudden death.^[1]

KCNQ1 (formerly called KVLQT1) is a voltage-gated potassium-channel gene responsible for the long QT 1 subtype of long QT syndromes. In general, heterozygous mutations in KCNQ1 cause Romano-Ward syndrome (LQT1 only), while homozygous mutations cause Jervell and Lange-Nielsen syndrome (LQT1 and deafness).^[2]

Attacks of ventricular tachyarrhythmia are usually associated with sympathetic stimulation such as exercise, stress or emotion, dependent on genotype.

Epidemiology

• The disorder may be sporadic or transmitted as an autosomal-dominant trait.
• Six different genes have so far been identified as being involved in the development of congenital long QT syndromes^[3] and heterozygote mutations in KCNQ1 (a potassium-channel gene) are thought to be responsible for Romano-Ward syndrome.^[2]

Presentation

• The severity ranges from those with no apparent symptoms to others who develop tachyarrhythmias resulting in episodes of syncope, cardiac arrest and, potentially, sudden death.
• Between such episodes, sinus bradycardia is often seen.
• There may be a family history of recurrent syncope or sudden death.

Differential diagnosis

Other causes of prolongation of the QT interval:

• Congenital: Jervell and Lange-Nielsen syndrome, which is associated with deaf mutism and transmitted as autosomal recessive.
• Acquired:
  • Electrolyte disturbances: hypokalaemia, hypocalcaemia, hypomagnesaemia.
  • Hypothermia.
  • Drugs:
    • Anti-arrhythmic drugs: amiodarone, sotalol, disopyramide.
    • Tricyclic antidepressants.
    • Non-sedative antihistamines: terfenadine, astemizole (both now withdrawn).
    • Antibiotic (erythromycin), and antimalarial (halofantrine).

Investigations

• The diagnosis should be considered in all patients who present with syncope.
• An ECG with calculation of the QT interval should be performed on all patients with a suggestive history.
• All other family members must be fully assessed.

Management

• Drug treatment:^[4]
  • Betablockers are the drugs of choice.
  • Betablockers are effective in preventing cardiac events in approximately 70% of patients.
  • Propranolol and nadolol are the betablockers most frequently used, but atenolol and metoprolol are also used.
• If drug treatment is unsuccessful then selective high left stellate ganglionectomy has been shown to be effective.^[5]
• Permanent pacing in combination with betablockers may also be effective in reducing symptoms.
• For high-risk patients, an implantable cardioverter defibrillator (ICD) reduces mortality.^[6]
• Defibrillator implantation is often a first-line therapy if there has been a cardiac arrest.

Prognosis

The prognosis of untreated congenital long QT syndrome is poor, with a high incidence of sudden death in childhood.