Andersen Tawil syndrome

Synonyms

4

Overview

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. These features often include a very small lower jaw (micrognathia), dental abnormalities, low-set ears, widely spaced eyes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal curvature of the spine (scoliosis).

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.

Symptoms

Anderson-Tawil syndrome 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 muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats can lead to discomfort, fainting, or cardiac arrest.

Physical abnormalities associated with Andersen-Tawil syndrome typically affect the head, face, and limbs. These features often include a very small lower jaw (micrognathia), dental abnormalities, low-set ears, widely spaced eyes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal curvature of the spine (scoliosis).

Anderson-Tawill syndroma is characterised by the following physical features:

  • short stature
  • scoliosis
  • low-set ears
  • hypertelorism
  • broad nasal root
  • micrognathia
  • clinodactyly
  • brachydactyly
  • syndactyly

Causes

The cause of the remaining cases remains unknown. 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. 

Diagnosis

The diagnosis of Andersen-Tawil syndrome might be suspected in individuals with either:

1. Two of the following three criteria:

  • Periodic paralysis
  • Symptomatic cardiac arrhythmias or evidence of enlarged U-waves, ventricular ectopy, or a prolonged QTc or QUc interval on electrocardiogram (ECG)
  • Characteristic facial features, dental abnormalities, small hands and feet, and at least two of the following:

                                        Low-set ears
                                        Widely spaced eyes
                                        Small lower jaw (mandible)
                                        Fifth-digit clinodactyly (curved pinky finger)
                                        Syndactyly

or

2. One of the above three criteria in addition to at least one other family member who meets two of the three criteria.

The presence of a mutation in the KCNJ2 gene confirms the diagnosis of Andersen-Tawil syndrome.

Treatment

Treatment depends on the individual and their reaction to potassium. Patients with severe arrhythmias may require a pacemaker.

The treatment of Andersen-Tawil syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists experienced in the treatment of periodic paralysis, cardiologists experienced in the treatment of long QT syndrome, and other healthcare professionals may need to systematically and comprehensively plan an affect child's treatment. Genetic counseling may be of benefit for affected individuals and their families.

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disorder, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Andersen-Tawil syndrome.

Affected individuals are encouraged to avoid potential triggers of periodic paralysis (e.g. rest following exercise or prolonged exercise). Avoidance of drugs that can prolong the QT interval is also recommended.

When periodic paralysis is associated with low potassium levels, treatment with oral supplemental potassium can be beneficial. In individuals prone to low potassium levels, daily potassium supplementation can be considered. Potassium supplementation may also shorten the QT interval, which can be of benefit for individuals who also experience a long QT interval.

A periodic paralysis episode that occurs when potassium levels are high usually resolve on their own within 60 minutes. However, eating carbohydrates or continuing mild exercise can shorten the duration of the episode.

Resources

  • NIH
  • Genetics Home Reference