Introduction
Andersen-Tawil syndrome is also referred to as Andersen syndrome and long QT syndrome 7. Andersen syndrome is a genetic disorder that affects various parts of the body. It is characterized by ventricular arrhythmias, developmental abnormalities, and sensitive periodic paralysis. The characteristic features of this disease were first described by Ellen Andersen in 1971, and Rabi Tawil made significant contributions to this. This article gives insight into the particulars of Andersen-Tawil syndrome.
What is Andersen-Tawil Syndrome?
Andersen-Tawil syndrome is a rare autosomal dominant disorder that affects various parts of the body. It is characterized by a triad of episodic muscle weakness; ventricular arrhythmias (abnormal heartbeat originating from lower heart chambers), and prolonged QT interval (measurement on electrocardiogram). It is also associated with developmental anomalies such as low-set ears, widely-spaced eyes, short stature, small mandible, fifth-digit clinodactyly, syndactyly, and scoliosis. It causes disturbances in the electrical function of the heart, characterized by a long QT interval in the electrocardiogram and abnormal heart rhythms. The affected individuals present with cardiac symptoms such as palpitations and syncope or muscle weakness that occurs after prolonged rest or after exertion. Mild permanent weakness, mild learning difficulties, and deficits in executive function and abstract reasoning have also been described.
What Are the Causes of Andersen-Tawil Syndrome?
Andersen-Tawil syndrome is an inherited disorder caused by a mutation in the KCNJ2 gene. This gene encodes an ion channel that transports potassium ions out of the cardiac muscle cells. This ion channel is essential for maintaining the normal functions of the skeletal and cardiac muscles. It is usually inherited from a parent in an autosomal dominant manner, but it can also occur due to a new genetic mutation. The mutation in Andersen-Tawil syndrome is of two types:
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Type I Syndrome: It is caused by a mutation in the KCNJ2 gene, and it accounts for about 60 percent of the cases.
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Type II Syndrome: It accounts for about 40 percent of the cases, and no mutations have been identified.
What Happens in Andersen-Tawil Syndrome?
Andersen-Tawil syndrome disturbs the electrical signals that coordinate the heart cells and increases the risk of abnormal heart rhythms. The genetic mutations cause a disturbance in the ion channels responsible for the flow of potassium and reduce the rate of repolarization of cardiac muscle cells. This is observed as a prolonged QT interval on the ECG (electrocardiogram). The prolonged QT interval results in arrhythmias. Muscle weakness is due to the depolarization of the resting membrane. The skeletal abnormalities seen in this syndrome are due to the impairment in the function of osteoclasts, cells that regulate bone growth, or disrupt the bone morphogenetic protein signaling cascade.
What Are the Clinical Manifestations of Andersen-Tawil Syndrome?
Andersen-Tawil syndrome is characterized by episodic flaccid muscle weakness, cardiac abnormalities, and distinctive dysmorphic features.
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Weakness - Intermittent weakness occurs spontaneously or may be triggered by prolonged rest or rest following exertion. The frequency, severity, and duration of the weakness vary by person. It presents with mild permanent weakness. However, fixed proximal weakness can also develop over a period of time.
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Ventricular Arrhythmias - Arrhythmias, including bidirectional ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular arrhythmias, may remain asymptomatic or manifest as palpitations. Less common presentations are syncope, cardiac arrest, or sudden death.
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Dilated Cardiomyopathy - It was observed in some cases and was reversed by treatment with Flecainide in an individual with a pathological variant of this disease. Dilated cardiomyopathy occurs as a consequence of chronic tachycardia rather than a primary phenotypic manifestation.
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Physical Features - It causes anomalies like low-set ears, widely-spaced eyes, fifth-digit clinodactyly, second and third-toe syndactyly, small mandible, short stature, broad nasal root, and scoliosis. It can also cause dental enamel discoloration. The characteristic facial features include a broad forehead, short palpebral fissures, a small upper jaw, and lower jaw, a thin upper lip, short palpebral fissures, and a triangular face. The dental findings include persistent primary teeth, dental crowding, and multiple missing teeth. Skeletal findings are fifth-digit clinodactyly (curved finger or toe) and second and third-toe syndactyly (fused fingers or toes). Other findings, such as small hands and feet and joint laxity, have also been observed. Renal abnormalities like unilateral hypoplastic kidney and renal tubular defect can also be present.
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Mild Learning Difficulties - In distinctive neurocognitive phenotype, mild learning difficulties and deficits in executive function and abstract reasoning have been observed. Developmental delay and growth restriction have also been observed.
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Afebrile Seizures - Some cases of afebrile seizures in infancy have been reported.
How Is Andersen-Tawil Syndrome Diagnosed?
The diagnosis of Andersen-Tawil syndrome is based on the symptoms, the clinical findings, and the results of the electrocardiogram. Clinical diagnostic criteria include the presence of periodic paralysis, ventricular arrhythmias, prolonged QT interval, the presence of developmental anomalies, and a family history of Andersen-Tawil syndrome.
Genetic testing helps to identify the type of mutations in the affected person. Other investigations include ambulatory ECG (electrocardiogram) to assess arrhythmias, measurement of potassium levels during the period of weakness, and thyroid function tests.
How Is Andersen-Tawil Syndrome Treated?
Andersen-Tawil syndrome is a genetic condition, and it cannot be cured. However, the symptoms of this syndrome can be successfully managed. It includes the following:
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General Measures - Medications that prolong the QT interval, including Sotalol and Amiodarone, should be avoided as they promote abnormal heart rhythms. Drugs that reduce potassium levels in the blood, such as diuretics, should be avoided as they worsen periodic paralysis and arrhythmias.
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Management of Arrhythmias - Taking beta blockers medications, such as Propranolol, blocks the effects of adrenaline on the heart. Other antiarrhythmic drugs like Flecainide and Verapamil also help in treating arrhythmias. An implantable cardioverter defibrillator is a small device implanted under the skin that detects abnormal arrhythmias and treats the arrhythmias with a small electric shock.
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Periodic Paralysis - Carbonic anhydrase inhibitors such as Acetazolamide help in the management of periodic paralysis.
Conclusion
Andersen-Tawil syndrome is a rare genetic disorder that affects various parts of the body. It is characterized by ventricular arrhythmias, developmental abnormalities, and sensitive periodic paralysis. Since Andersen-Tawil syndrome is caused by genetic mutations, it cannot be cured. However, the symptoms can be managed, and the worsening of the disease can be prevented. Early diagnosis and management are essential for a good treatment outcome. The affected patients respond well to treatment and show good outcomes.
