Andersen-Tawil syndrome: Year of the Zebra 2025

Andersen-Tawil syndrome, or ATS for short, is a rare genetic disorder that affects the heart and skeletal muscles. It’s part of a group of conditions known as channelopathies, which are all caused by problems with ion channels—the proteins that control the flow of ions, like sodium or potassium, in and out of cells. These channels help reset the electrical state of muscle cells after a contraction by allowing potassium ions to flow out, enabling the cell to get ready for the next contraction.

Specifically, most cases of ATS are caused by mutations in the KCNJ2 gene, which affects the function of potassium channels in muscle and heart cells. When potassium channels don’t work properly, muscle cells may become overly excitable or fail to reset properly after firing. In skeletal muscles, this may result in sudden episodes of muscle weakness, whereas in the heart, it may lead to abnormal heart rhythms, called arrhythmias.

Signs and symptoms typically consist of the triad of weakness or paralysis; abnormal heart rhythms; and distinct facial features. Clinically, individuals with ATS have sudden episodes of muscle weakness or full paralysis, usually affecting the limbs. These episodes are often triggered by rest following exercise, emotional stress, prolonged fasting, or a high sugar intake, which can lead to a spike in insulin followed by potassium shifts in the blood.

Individuals are also at increased risk of abnormal heart rhythms, specifically ventricular tachycardia, a rhythm that can cause the heart rate to rise above 250 beats per minute. If this happens, an individual can have symptoms of decreased blood supply to the brain and other organs, such as chest pain, fainting, dizziness, or shortness of breath. It can even cause sudden death.

Finally, individuals with ATS often have distinctive facial features, including a broad forehead, wide-set eyes, low-set ears, short stature, scoliosis, or curved fingers and toes, although not all individuals show these signs.

Diagnosis of ATS can be challenging because the symptoms are varied and not everyone presents with the classic triad.

Often, an ECG is the first key test to reveal anomalies. Sometimes, an exercise ECG or 24-hour Holter monitor is used to catch intermittent arrhythmias.

Genetic testing confirms the diagnosis in most cases, however, around 30% of individuals with classic symptoms don’t have identifiable mutations, so diagnosis remains clinical in those cases.