DNA tests lead to early discovery of Sudden Arrhythmia Death Syndrome
DNA tests can lead to early discovery, and treatment, of conditions such as Sudden Arrhythmia Death Syndromes that can strike without warning
Before Jennifer's mother died in 2005, she would often faint early in the morning. Her family had no idea what was causing the fainting spells, but the last time it happened, the 53-year-old lapsed into a coma for six months and died.
It was while she was in a coma when doctors found the cause: she suffered from Long QT Syndrome, a rare congenital disorder of the heart's electrical system that predisposes sufferers to irregular heartbeats, fainting spells and sudden death. There's a 50/50 chance that the condition will pass from an affected parent to child, so Princess Margaret Hospital ran a DNA test on Jennifer and found that she also suffered from the condition.
"Many members of my family were DNA tested. My younger sister and I, my son, and my younger sister's twin girls have it; my mum's siblings have been spared. There's no cure for the condition, but I am taking drugs to keep it under control," says Jennifer.
"It turned out the shrill ringing of the alarm clock caused my mum's fainting spells, so I stopped using an alarm clock, and I avoid strenuous exercise, too. I have taken all the right precautions, and I am glad that I can live like an ordinary person."
Between 2008 and 2012, 289 young people aged from five to 40 died because of heart diseases. Seventy-two of the victims, or 25 per cent, were found to suffer from Sudden Arrhythmia Death Syndromes (Sads), a group of inherited cardiac rhythm disorders that can sometimes cause sudden cardiac death.
However, DNA tests conducted at specialist labs such as the one at Princess Margaret Hospital help provide early diagnoses for congenital neurological, heart and paediatric diseases, says Chloe Mak Miu, consultant pathologist at the hospital.
The lab runs 300 DNA tests a year, and "over 10 are for rare heart diseases".
The human nuclear genome, which was fully sequenced in 2003, contains three billion DNA bases that make up approximately 25,000 genes, Mak says. Mutations in the genes lead to hereditary diseases such as Huntington's disease
Professor Tse Hung-fat, specialist in cardiology with Queen Mary Hospital, which also conducts DNA testing for heart diseases, says DNA tests help the early discovery of Sads and stop lives being cut short.
"Some patients die from the first attack, and DNA tests can make diagnoses for those who have yet to suffer from that first attack. For some, the condition remains hidden unless triggered by the external environment," Tse says.
DNA tests and the study of rare congenital heart diseases got a big boost recently following a donation to the Hospital Authority by businesswoman Shirley Chan Chow. Chan set up the Sads Hong Kong Foundation after her son died suddenly last year (story below).
Tse says the post-mortem DNA tests carried out in 2013 to find the cause of Chan's son's death were the first of their kind performed in Hong Kong.
"The cause was found to be Brugada Syndrome, a form of Sads," Tse explains. "But such post-mortem DNA tests are difficult to do. They could be carried out on Chan's son because his dad suffered from the same condition.
"We were also lucky to have an electrocardiogram of the son. From the electrocardiogram, we could make a guess about the condition. If two patients in the same family have the same condition, and carry the same mutated gene, we can do the test," adds Tse.
Sads involves two types of patients, says Tse. One type suffers from structural heart diseases like hypertrophic cardiomyopathy (the heart muscle becomes thick). The other kind suffers from non-structural heart diseases. For that type, an autopsy on the heart won't find an abnormality because problems with the electrical pathways in the heart cause the sudden death.
"There are around five types of these electrical pathway heart problems, including Long QT Syndrome and Brugada Syndrome. Some 20 to 30 mutated genes can cause hypertrophic cardiomyopathy; more than 10 gene mutations lead to Long QT Syndrome," says Tse.
"Only 20 per cent of Brugada cases can be traced to the known mutated genes, with 70 per cent of cases remaining unknown. If there's no living relative of the diseased patient, or an existing electrocardiogram, we can only do blind DNA testing, testing all the genes. That is very expensive, and the yield is very low.
"In many of the patients I saw, their parents had died very young and they had no relatives with the condition. DNA testing is difficult to do in such circumstances," Tse says.
But Dr Mok Ngai-shing, consultant cardiologist and head of the cardiac team at Princess Margaret Hospital, says better procedures can be put in place to improve molecular autopsies of patients who died from unknown causes. "I have been collaborating with forensic pathologists for the last six months. They are always looking for help if they can't find the reason for a death after an autopsy, as it means that they can't give an explanation to family members. DNA tests are one of the ways to find a cause of death. The Hospital Authority has not yet got the mechanism to do it," he says.
"In Chan's son's case, [the body] was immersed in preservatives for some time, which had destroyed some of the DNA, something which makes our work more difficult. If we need to do the test, we must get fresh blood from the dead person and avoid immersing the tissue in preservatives."
With the support of the Sads Foundation, Mok will start a two-year project next year to study the prevalence and types of Sads as the underlying causes of sudden death among young local victims. The study involves 40 sudden death victims and about 160 relatives of these victims. The study will include molecular autopsies of the victims, and DNA tests on the relatives.
"Instead of trying each of the genes suspected of causing the condition as before, Hong Kong has taken a new technology from the West called 'next generation sequencing'.
"This is a broad screening of all the related genes. If we can find data from the two-year study to support this new technology, we have a better case to go to the Hospital Authority and ask for it to be funded for widespread application," says Mok.
Adds Tse: "Relatives of those who suffer from sudden death do not know such methods are available to check whether they also suffer from the congenital condition. These tests can prevent similar tragedies befalling them."
Mok says the results from the genetic tests can also help Hong Kong set up a database of rare diseases that affect local people.
"Hong Kong lacks a database for rare congenital diseases. This does not just concern heart diseases.
"Genetic diseases [caused by DNA mutations] are specific to different races. A database could help ascertain what kinds of congenital diseases afflict Hong Kong people," Mok says.