What is Andersen-Tawil syndrome

TL;DR: Andersen-Tawil syndrome is a rare genetic disorder characterized by the classic clinical triad of episodic muscle weakness (periodic paralysis), heart rhythm irregularities, and distinct physical features. It is a subtype of potassium-sensitive periodic paralysis, typically caused by mutations in the KCNJ2 gene that affect electrical signaling in the heart and muscles.

What is Andersen-Tawil syndrome?

Andersen-Tawil syndrome, also known as Long QT syndrome type 7, is a multisystem condition that disrupts the body's ability to regulate potassium flow in cells. Because potassium is essential for electrical signaling, Andersen-Tawil syndrome primarily impacts the skeletal muscles and the heart. At DiseaseMaps.org, 32 people with Andersen-Tawil syndrome have joined our community to share their experiences, highlighting that while the condition is rare, patients benefit significantly from connecting with others navigating similar diagnostic journeys.

Which body systems are affected by Andersen-Tawil syndrome?

The clinical presentation of Andersen-Tawil syndrome is defined by a triad of symptoms, though not every patient will experience all three to the same degree:

• Episodic Muscle Weakness: Known as periodic paralysis, these episodes can last from hours to days and are often triggered by rest following exercise, stress, or high-carbohydrate meals.


• Cardiac Arrhythmias: Patients often exhibit a prolonged QT interval on an EKG, which increases the risk of dangerous heart rhythm disturbances (ventricular arrhythmias).


• Distinctive Physical Features: Individuals may present with low-set ears, a wide-set distance between the eyes (hypertelorism), a small lower jaw (micrognathia), and sometimes clinodactyly (curved fingers or toes).

How common is Andersen-Tawil syndrome and who is affected?

Andersen-Tawil syndrome is an ultra-rare condition. While exact global prevalence is difficult to determine due to underdiagnosis, it is estimated to affect approximately 1 in 1,000,000 people. It affects males and females equally, and symptoms typically emerge during childhood or adolescence. There are no known geographic or ethnic predilections for the disorder, though it is often under-recognized in clinical settings due to the variability of symptoms.

What causes this condition and how is it inherited?

The majority of Andersen-Tawil syndrome cases are caused by mutations in the KCNJ2 gene, which provides instructions for making a protein that forms potassium channels in cell membranes. These channels act as "gates" to control the flow of potassium ions. In Andersen-Tawil syndrome, these channels do not function correctly, leading to electrical instability. The condition follows an autosomal dominant inheritance pattern, meaning a person only needs one copy of the mutated gene from one parent to develop the disorder, though many cases occur as a de novo (spontaneous) mutation in individuals with no family history.

How does it differ from other periodic paralyses?

What sets Andersen-Tawil syndrome apart from other forms of periodic paralysis is the presence of cardiac involvement and the characteristic physical features. Unlike other types of hypokalemic periodic paralysis, the cardiac rhythm issues in this syndrome require specialized cardiological monitoring, such as Holter monitoring or stress testing, to ensure patient safety and prevent sudden cardiac events.

Next steps

• Consult a specialized cardiologist or a neuromuscular neurologist familiar with channelopathies.


• Request a referral to a clinical geneticist for genetic testing to confirm the KCNJ2 mutation.


• Join the DiseaseMaps.org community to connect with other patients and caregivers.


• Carry an updated list of medications to avoid, as some drugs can worsen electrical instability in the heart.

Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Andersen-Tawil Syndrome Overview.


• Orphanet: Periodic paralysis, Andersen-Tawil type (ORPHA:84).


• OMIM (Online Mendelian Inheritance in Man): Andersen-Tawil Syndrome (#170390).


• GeneReviews: KCNJ2-Related Andersen-Tawil Syndrome.