Brugada syndrome

Brugada_EKG_SchemaBrugada syndrome is an inherited condition with a specific abnormal heartbeat, called a Brugada sign (shown on side B in opposite image of a ECG [Echocardiogram]), which causes the lower ventricles of the heart to beat so fast that the blood cannot circulate throughout the body well. This irregular heart rhythm can cause fainting or sudden cardiac arrest — most often in healthy individuals. The Brugada syndrome is also known as SUDS (Sudden Unexplained Death Syndrome) and SADS (Sudden Adult Death Syndrome) and is most common in people of Asian ancestry (particularly men).

Approximately 20% of the cases to date of Brugada syndrome have been shown to be associated with mutations in the gene that encodes for the sodium ion channel in the cell membranes of the muscle cells of the heart (the myocytes). Scientists have found the following genes to play a role in triggering Brugada syndrome: SCN5A (which is located on the short arm of the third chromosome (3p21) and over 160 mutations of this gene have been discovered to date) and GPD1L. All of the patients studied, that had undergone a detailed autopsy upon death (due to the mutation resulting from gene SCN5A) had a right ventricular pathology.

An example of one of the mechanisms by which a loss of function of the sodium channel occurs is a mutation in the gene that disrupts the sodium channel’s ability to bind properly to ankyrin-G, an important protein mediating interaction between ion channels and cytoskeletal elements. Very recently a mutation in a second gene, Glycerol-3-phosphate dehydrogenase-1-like gene (GPD1L) has been shown to result in Brugada syndrome in a large multigenerational family (London, 2006). This gene acts as an ion channel modulator in the heart, although the exact mechanism is not yet understood.

Recently researchers (Antzelevitch) have identified mutations in the L-type calcium channel sub-units leading to ST elevation and a relatively short QT interval (below 360 ms). In 2013, Bezzina et al. showed that common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome as well.

Brugada syndrome can be diagnosed with the aid of Electrocardiography (ECG) and has three different ECG patterns.

  • Type 1 has a curved type ST elevation with at least 2 mm (0.2 mV) J-point elevation and a gradually descending ST segment followed by a negative T-wave.
  • Type 2 has a saddle back pattern with a least 2 mm J-point elevation and at least 1 mm ST elevation with a positive or Biphasic T-wave. Type 2 pattern can occasionally be seen in healthy subjects.
  • Type 3 can be a mixture of Type 1 and 2, but it’s important to note that the pattern is usually less than 2 mm J-point elevation and less than 1 mm ST elevation. It is also, not uncommon in healthy subjects.

The cause of death in Brugada syndrome is ventricular fibrillation. The episodes of syncope (fainting) and sudden death (aborted or not) are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning. While there is no exact treatment modality that reliably and totally prevents ventricular fibrillation from occurring, treatment lies in termination of this lethal arrhythmia before it causes death. Recent studies have evaluated the role of Quinidine for decreasing VF episodes occurring in this syndrome. The drug has been found to both decrease the number of VF episodes and correct spontaneous ECG changes.

Sources

http://www.christianacare.org/types-of-inherited-heart-disease

http://www.ucsfhealth.org/conditions/hypertrophic_cardiomyopathy/index.html

http://en.wikipedia.org/wiki/Brugada_syndrome