What is the management of Anderson-Tawil syndrome?

From the Guidelines

The management of Anderson-Tawil syndrome should focus on treating cardiac arrhythmias, periodic paralysis, and other symptoms, with beta-blockers as the first-line treatment for cardiac manifestations, as recommended by the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

Key Considerations

• The syndrome is characterized by a prolonged QT interval with prominent U wave, polymorphic or bidirectional VT, facial dysmorphisms, and hyper-/hypokalemic periodic paralysis.
• Beta-blockers, such as propranolol or nadolol, are recommended to reduce ventricular arrhythmias, with a dose range of 40-320 mg/day for propranolol or 40-160 mg/day for nadolol.
• For patients with significant ventricular arrhythmias not controlled by beta-blockers, flecainide or other class Ic antiarrhythmics may be added, as suggested by the guidelines for LQTS3 patients with a QTc ≥500 ms 1.

Treatment Approach

• Calcium channel blockers like verapamil can also be effective in managing cardiac symptoms.
• For periodic paralysis episodes, carbonic anhydrase inhibitors such as acetazolamide or dichlorphenamide are commonly used, with potassium supplementation as needed.
• In patients with severe cardiac symptoms or those at high risk for sudden cardiac death, an implantable cardioverter-defibrillator (ICD) may be necessary, as recommended by the guidelines for LQTS patients with previous cardiac arrest 1.

Multidisciplinary Management

• Treatment should be individualized based on symptom severity, with regular cardiac monitoring including ECGs and Holter monitoring.
• Physical therapy may benefit patients with persistent muscle weakness, while avoiding triggers like strenuous exercise and extreme temperatures can help prevent paralytic attacks.
• Management requires a multidisciplinary approach involving cardiologists, neurologists, and geneticists due to the syndrome's complex multi-system nature.

From the Research

Management of Anderson-Tawil Syndrome

The management of Anderson-Tawil syndrome (ATS) is challenging and requires a comprehensive approach.

• The choice between antiarrhythmic drug therapy and implantable cardioverter defibrillator (ICD) is not simple, as reported in a case study 2.
• Flecainide therapy has been used to control episodes of bidirectional ventricular tachycardia in some patients 2.
• Antiarrhythmic drugs are required in 39.1% of patients with cardiac abnormalities, as observed in a French cohort of ATS patients 3.
• Acetazolamide has been reported to have a good neuromuscular response in 67% of patients treated 4.

Cardiac Management

• Cardiac abnormalities are observed in 65.7% of ATS patients, with 56.5% being asymptomatic and 39.1% requiring antiarrhythmic drugs 3.
• Baseline electrocardiograms are not helpful in stratifying cardiac risk, but Holter monitoring is useful 4.
• Loop recorders can be used to guide management in asymptomatic patients with abnormal Holter monitor recordings 4.
• ICD implantation is required in 13% of patients, and an additional 23% report syncope 4.

Neuromuscular Management

• Periodic paralysis is present in 80% of ATS patients, and common triggers include exercise, immobility, and carbohydrate-rich diet 3.
• Permanent weakness affecting proximal muscles is observed in 45.7% of patients, which can be mild and stable or slowly progressive over several decades 3.
• ENMG long-exercise test has a high diagnostic yield and should be performed to diagnose ATS 3.
• Muscle biopsy can reveal tubular aggregates, dystrophic features, or non-specific myopathic features, emphasizing the active myopathic process underpinning the potential for severe neuromuscular disability 3, 4.