Romano–Ward syndrome

Overview

Romano–Ward syndrome is the most common form of congenital long QT syndrome (LQTS), a genetic disorder that affects the heart’s electrical system. It is characterized by a prolonged QT interval on an electrocardiogram (ECG), which reflects delayed repolarization of the heart after a heartbeat. This abnormality can lead to life-threatening arrhythmias such as torsades de pointes and sudden cardiac arrest, particularly in response to stress, exercise, or certain medications.

Romano–Ward syndrome is inherited in an autosomal dominant manner and occurs without other physical abnormalities, distinguishing it from Jervell and Lange-Nielsen syndrome, which includes hearing loss. Although the condition may be asymptomatic in some individuals, early diagnosis and appropriate management are critical to reducing the risk of sudden death.

Causes

Romano–Ward syndrome is caused by mutations in genes that encode ion channels responsible for the electrical activity of the heart. These mutations affect the flow of potassium, sodium, or calcium ions, disrupting the normal repolarization of the heart muscle after each beat.

Common Genetic Mutations:

• KCNQ1 (LQT1): Affects potassium channels, the most common subtype

• KCNH2 (LQT2): Another potassium channel gene

• SCN5A (LQT3): Affects sodium channels and is associated with events during rest or sleep

Inheritance Pattern:

• Romano–Ward syndrome follows an autosomal dominant inheritance pattern

• Each child of an affected parent has a 50% chance of inheriting the mutation

Symptoms

Symptoms of Romano–Ward syndrome vary widely among individuals. Some may never experience any symptoms, while others may present with serious arrhythmic events early in life. The symptoms often result from abnormal heart rhythms that reduce blood flow to the brain and other vital organs.

Common Symptoms:

• Syncope (fainting): Often triggered by exercise, emotional stress, or loud noises

• Palpitations: Sensation of rapid or irregular heartbeat

• Seizure-like episodes: Due to reduced blood flow to the brain, sometimes misdiagnosed as epilepsy

• Sudden cardiac arrest: Often the first and sometimes fatal sign in undiagnosed cases

Trigger-Specific Risk by Genotype:

• LQT1: Events often triggered by physical activity, especially swimming

• LQT2: Triggers include sudden noises or emotional stress

• LQT3: Events commonly occur during rest or sleep

Diagnosis

Diagnosis of Romano–Ward syndrome is based on clinical evaluation, ECG findings, family history, and genetic testing. It is essential to identify at-risk individuals, even if they are asymptomatic, especially in families with a history of sudden cardiac death.

Electrocardiogram (ECG):

• Shows a prolonged corrected QT interval (QTc), generally > 460 ms in females and > 450 ms in males

• T-wave abnormalities such as notching or low amplitude

Holter Monitoring:

• 24- to 48-hour ECG monitoring to detect transient arrhythmias

Exercise Stress Test:

• Used to evaluate QT interval behavior during and after exercise, especially in suspected LQT1

Genetic Testing:

• Confirms the diagnosis by identifying mutations in LQTS-associated genes

• Important for cascade screening of family members

Family History and Risk Stratification:

• Detailed family history of unexplained fainting, seizures, or sudden cardiac death

• Schwartz score may be used to assess likelihood of LQTS based on clinical and ECG features

Treatment

The goal of treatment in Romano–Ward syndrome is to prevent arrhythmic events and sudden death. Management strategies depend on the severity of symptoms, QT interval duration, and genotype. Lifestyle modifications, medications, and device therapy may all play a role.

1. Lifestyle Modifications:

• Avoid strenuous exercise, especially swimming (in LQT1)

• Minimize exposure to sudden loud noises (in LQT2)

• Prevent electrolyte imbalances, particularly low potassium or magnesium

• Avoid QT-prolonging medications (e.g., certain antibiotics, antihistamines, antipsychotics)

2. Medications:

• Beta-blockers: First-line therapy (e.g., propranolol, nadolol); reduce risk of arrhythmias by blunting the adrenergic response

• Sodium channel blockers: (e.g., mexiletine) may be useful in LQT3

3. Device Therapy:

• Implantable cardioverter-defibrillator (ICD): Indicated in patients with a history of cardiac arrest or high-risk syncope

• Pacemakers: May be considered in bradycardia or high-risk LQT3 cases

4. Left Cardiac Sympathetic Denervation (LCSD):

• A surgical option in high-risk patients who are not candidates for ICD or have breakthrough events despite medication

Prognosis

The prognosis of Romano–Ward syndrome varies depending on the specific genetic mutation, QT interval duration, and the effectiveness of treatment. With early diagnosis and appropriate therapy, most individuals can live long and healthy lives.

Without treatment, the risk of sudden cardiac death can be significant, particularly in individuals with a history of syncope or those with a markedly prolonged QT interval. Genotype-specific risk assessment and management have significantly improved outcomes.

Ongoing monitoring, genetic counseling, and education are essential components of long-term care. Family members of affected individuals should be screened to identify those at risk and initiate early preventive measures.