Romano-Ward syndrome

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

What is Romano-Ward 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 (long QT only), while homozygous mutations cause Jervell and Lange-Nielsen syndrome (long QT and deafness).² Heterozygous mutations in KCNE1, another voltage-gated potassium channel gene, have also been implicated in Romano-Ward syndrome, causing the long QT 5 subtype.³⁴

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

How common is Romano-Ward syndrome? (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 syndromes⁵ and heterozygote mutations in KCNQ1, KCNQ1 (potassium-channel genes), and other long QT-associated genes, are thought to be responsible for Romano-Ward syndrome.³

Symptoms of Romano-Ward syndrome (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    • Non-sedative antihistamines: terfenadine, astemizole (both now withdrawn).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).

Diagnosing Romano-Ward syndrome (investigations)

• The diagnosis should be considered - along with other causes of cardiogenic syncope - in patients who present with syncope.

• Syncope triggered by exertion, loud noises, or emotion are all concerning for long QT syndrome.

• Some individuals will have a family history of sudden unexplained death.

• 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.

• Genetic testing can confirm the diagnosis and establish the specific genotype.

Managementof Romano-Ward syndrome⁶

• Drug treatment:

  • Beta blockers are the drugs of choice.

  • Beta blockers are effective in preventing cardiac events in approximately 70% of patients. Many cardiac events that occur in people with long QT syndrome who are 'on beta blockers' occur due to non-adherence with the medication, and/or taking QT-prolonging drugs.

  • Longer-acting beta-blockers are preferred, to facilitate adherence.

• QT-prolonging drugs must be used with extreme caution, and should only be given after careful consideration of the risk/benefit balance.

• If drug treatment is unsuccessful then selective high left stellate ganglionectomy has been shown to be effective.⁷

• Permanent pacing in combination with betablockers may also be effective in reducing symptoms.

• For high-risk patients, an implantable cardioverter defibrillator (ICD) reduces mortality.⁸

• 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.