Quick Parent’s Guide on Genetic Testing in Hong Kong
This is a quick guide about genetic testing in Hong Kong based on parents’ experience. It is very challenging to need to deal with the whole world collapsing while talking to doctors and making decisions about what tests to take. In an ideal world the doctors will proactively and patiently explain possible test options to patient families, but language may sometimes be a barrier or simply that the doctor has already had a long day. Research shows that families prefer to have a diagnosis so they can plan ahead better. It is also advantageous for the hospital as early diagnosis will enable more efficient treatment and symptom management[1]. The teaching hospitals in Hong Kong have strong academic research teams and they are well funded so that children may be eligible for free genetic testing (sometimes the parents’ blood samples will be taken for the child’s test). Even if your child is not seen at a teaching hospital, the public hospital doctors should be in a position to connect the child with research teams. Therefore, it is important that families are aware of what is available and are able to ask specifically.
MAJOR GENETIC TESTS
Single Gene Testing
Mutations in a single gene, e.g. SCN1A (for Dravet Syndrome) can be detected by single gene tests. Doctors may order single gene tests based on clinical observations and experience. As this is one gene at a time, a “negative” test result does not guarantee that the child is free of genetic diseases. A negative result simply means the child does not have the condition which single gene test screen for.
Chromosomal Microarray Testing
For children born with visible disabilities, a Chromosomal Microarray (CMA) test may be ordered by the doctors. It screens for anomalies such as duplication and deletion at the chromosome level. For example, Down Syndrome is the presence of a third copy of chromosome 21 (there should only be two). There are other chromosomal disorders such as trisomy 18, chromosome 22 deletion, etc. Anomalies at the gene level or microdeletions may not be detected by this test. Therefore, it is possible that when a child clearly has a genetic disease but this test “finds nothing”.
Gene Panel Testing
You may have heard other parents talking about an “epilepsy panel” or “mito panel (for mitochondrial diseases)”. Sometimes, a doctor will recommend a gene panel for certain group of diseases based on clinical findings, e.g. a child with exceedingly low muscle tone at birth may have a neuromuscular disease and the doctor may order a corresponding gene panel test for the child. The coverage of a gene panel can range from a few genes to a few hundred genes. There are commercially available gene panels. There are funded gene panel testing in certain teaching hospitals and it is also available privately. Parents should request the ordering physician to explain clearly as to what the test covers.
Whole Exome Sequencing (WES)
WES has become a more accessible option in the recent decade. With an ever-expanding database, the diagnostic yield (linking exon anomalies to a diagnosis) has been increasing. The test focuses on problems with exons (encoding part of DNA). While patients may be selected to be included in funded research programs in public hospitals, self-financed WES can be ordered by private doctors.
Whole Genome Sequencing (WGS)
In addition to exon, WGS looks into intron and codon (the non-encoding elements in DNA). This may be pursued if WES yields nothing.
WHICH TEST TO TAKE FIRST?
In terms of coverage or chance of finding something, one may think about the various tests in the following order:
Single gene < CMA ~ Gene Panel (the two tests check at different levels) < WES < WGS
If a single-gene test comes back positive, i.e., the doctor’s estimate was accurate, then no more genetic testing is necessary (unless for academic purposes and such testing should be free of charge for the family).
As for CMA and gene panel, the advantage is that a range of diseases can be checked at the same time. No doubt the chance of finding something will be higher than trying gene by gene. Some families choose to pursue no more genetic testing after CMA or a panel while others would like to have a confirmed diagnosis for reasons such as finding peer support, additional prognostic information and more precise treatment, e.g., common antiseizure medications (sodium channel blockers) may make patients with Dravet syndrome worse rather than better. There is now great research efforts on specific rare diseases and new data make precision medicine possible. There may not be a cure today, but at least known harm can be avoided to minimise negative effects of treatment on the patient.
One may ask if WGS should be the starting point. It is not impossible but it may be an overshoot. WGS takes a longer time, is more costly and does not necessarily lead to a diagnosis. At present, the sweet spot seems to be at WES especially when there is funding at the university level. An offer for free panel testing is equally helpful.
HOW LIKELY IS A DIAGNOSIS FOUND BY WES?
There is roughly 30% chance for WES to confirm an epileptic syndrome diagnosis and approximately 50% for certain cardiovascular condition. On the other hand, there has yet to be a gene or a group of genes that can be linked to autism. So a family may want to think twice about spending on genetic testing to confirm autism.
IS IT WORTHWHILE TO TAKE A GENETIC TEST AGAIN IF THE FIRST WES FOUND NOTHING?
What is noteworthy is that genetic testing and research is dynamic. There will be a new entry every time a new genetic anomaly is implicated, meaning there will be more reference materials for new tests. As a result, what WES couldn’t find five years ago may yield something today. Sometimes there are a few phenotypes for a specific genetic anomaly, i.e., not everyone with the same mutation will have a disability. For example, there is SCN2A mutation with autism only, SCN2A with epilepsy only and SCN2A with both epilepsy and autism. These variations are called phenotypes. It takes time for clinical data to be documented and analysed. This further highlights the importance of pursuing genetic testing as clinical observation can only reveal so much.
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