What is Andersen-Tawil syndrome?
Anderson-Tawil syndrome is a disorder that causes episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities.
The most common changes affecting the heart are ventricular arrhythmia, which is a disruption in the rhythm of the heart’s lower chambers, and long QT syndrome. Long QT syndrome is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats can lead to discomfort, fainting (syncope), or cardiac arrest.
Physical abnormalities associated with Andersen-Tawil syndrome typically affect the head, face, and limbs.
Two types of Andersen-Tawil syndrome are distinguished by their genetic causes. Type 1, which accounts for about 60 percent of all cases of the disorder, is caused by mutations in the KCNJ2 gene. The remaining 40 percent of cases are designated as type 2; the cause of these cases is unknown.
How common is Andersen-Tawil syndrome?
Andersen-Tawil syndrome is a rare genetic disorder. Its incidence is unknown. About 100 people with this condition have been reported worldwide.
What genes are related to Andersen-Tawil syndrome?
Mutations in the KCNJ2 gene cause Andersen-Tawil syndrome.
The KCNJ2 gene provides instructions for making a protein that forms a channel across cell membranes. This channel transports positively charged atoms (ions) of potassium into muscle cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of muscles used for movement (skeletal muscles) and cardiac muscle. Mutations in the KCNJ2 gene alter the usual structure and function of potassium channels or prevent the channels from being inserted correctly into the cell membrane. Many mutations prevent a molecule called PIP2 from binding to the channels and effectively regulating their activity. These changes disrupt the flow of potassium ions in skeletal and cardiac muscle, leading to the periodic paralysis and irregular heart rhythm characteristic of Andersen-Tawil syndrome.
Researchers have not determined the role of the KCNJ2 gene in bone development, and it is not known how mutations in the gene lead to the developmental abnormalities often found in Andersen-Tawil syndrome.
How do people inherit Andersen-Tawil syndrome?
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, a person with Andersen-Tawil syndrome inherits the mutation from one affected parent. Other cases result from new mutations in the KCNJ2 gene. These cases occur in people with no history of the disorder in their family.
Are there any symptoms?
Andersen-Tawil syndrome is characterized by a triad of episodic flaccid muscle weakness (i.e., periodic paralysis), ventricular arrhythmias and prolonged QT interval. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or fainting) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described.
Other characteristics include:
- Widely spaced eyes
- Short stature
- Scoliosis
- Webbed toes or fingers
- Unusual short fingers
- Low set ears
- Broad forehead
- Small jaw
- Protruding jaw
- Broad nasal root
What is a treatment option for Andersen-Tawil Syndrome?
For episodic weakness:
- if serum potassium concentration is low (
- if serum potassium concentration is high, ingesting carbohydrates or continuing mild exercise may shorten the attack.
Source: Genetics Home Reference and Gene Reviews
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