SNP Shot: Genomic Insights

Andersen-Tawil syndrome is a condition characterized by attacks of muscle weakness (known as periodic paralysis), irregular heart rhythms (arrhythmias), and certain developmental differences. The periodic paralysis typically starts early in life, with episodes that can last for hours or even days. These episodes may be triggered by exercise or prolonged inactivity, but often occur without any clear cause. Muscle strength usually returns to normal between attacks, although some people may eventually develop permanent, mild muscle weakness.

Heart problems in individuals with Andersen-Tawil syndrome commonly include ventricular arrhythmia, an irregular rhythm in the lower chambers of the heart (ventricles), and long QT syndrome. Long QT syndrome is a cardiac condition where the heart muscle takes longer than normal to recover between beats. These irregular heartbeats can cause palpitations and, less commonly, fainting (syncope). In rare instances, they can even lead to sudden death.

Andersen-Tawil syndrome is also associated with physical differences, most often affecting the face, head, and limbs. These can include a small lower jaw (micrognathia), dental issues (like crowded teeth), low-set ears, wide-set eyes, fusion of the second and third toes (syndactyly), and unusual curvature of the fingers or toes (clinodactyly). Some individuals may also have short stature and an abnormal curvature of the spine (scoliosis).

The symptoms of Andersen-Tawil syndrome can vary considerably from person to person, even within the same family. Approximately 60% of those affected exhibit all three major features: periodic paralysis, heart arrhythmia, and physical abnormalities.

Inheritance:

Andersen-Tawil syndrome is typically inherited in an autosomal dominant manner. This means that having just one copy of a changed (mutated) gene in each cell is enough to cause the condition. When the syndrome is caused by a mutation in the KCNJ2 gene, an affected person may inherit this mutation from a parent who also has the condition. However, in some cases, the mutation in the KCNJ2 gene arises spontaneously (de novo) in a person with no family history of the disorder.