- What’s new for people with, or at risk of, HSP?
- What kinds of tests are there?
- What is the testing process?
- What is screening and how is it different from testing?
- My neurologist has already told me I have HSP. Why do I need more tests?
- When I know my mutation how is it going to help me?
- How do I get started?
- How can my partner and I prevent our children inheriting HSP?
- What are the benefits of gene testing?
- Are there risks or issues associated with gene testing?
- What is a gene and what is a mutation?
What’s new for people with, or at risk of, HSP?
Genetic testing for HSP is available Australia-wide. There are 3 facilities that offer state-of-the-art next-generation testing for 50 or more HSP mutations. The HSP testing ‘panel’ can be added to and updated as new mutations are discovered and documented. With next-generation sequencing, the panel with the information on HSP mutations is contained in a software application. Mutations are identified by digitally ‘filtering’ an individual’s exome or genome data against the panel. More than 70 HSP mutation loci are now known.
Although a huge advancement, next-generation sequencing is far from comprehensive or ideal. Certain types of mutations are not detected, meaning that traditional ‘hand sequencing’ technology is required as an adjunct in a significant percentage of cases.
Overall, about half of all HSP cases are now identified by gene testing, which is a big improvement compared to traditional methods… and there is still a long way to go. Modern technologies have enabled a more accurate and comprehensive picture of HSP genetics to be developed and that picture is increasingly being found to be more complex than previously thought.
What kinds of tests are there?
There are 2 types of tests… one called testing and the other called screening. The first is a test to discover the causal mutation of HSP in an individual. The second is called screening, and this means that blood relatives of someone whose mutation is known are screened for the presence or absence of that mutation. Testing is more expensive than screening as testing involves searching for an HSP mutation. When a family mutation is known, screening involves going straight to the location of that mutation to check if it is present in other blood relatives. This is a simpler, easier and faster process… and therefore cheaper.
Testing for research purposes
Neurologists will sometimes ask an HSP patient if they can take a blood sample to have gene testing done for research purposes. It is important for HSPers to understand that the results of any such testing for research purposes will never be available to them due to the ethics considerations that require research samples to not be personally identifiable. However, in such cases, repeat testing can be done so that the information on any HSP mutation discovered is available and can be shared.
What is the testing process?
Full details of testing services and how to go about getting tested are available here.
Tests for discovery/detection of a mutation
This is the first step in determining the cause of the disorder in a family. It is conducted via a blood sample of a single, family representative with the disease. The purpose of the test is to detect the particular HSP mutation by discovering the aberrant coding sequence and type of mutation.
The clinical geneticist or neurologist will nominate the type of test to be conducted based on factors such as the type of HSP the patient may appear to have, family history and prevalence of different HSP genes (SPG4 is the most prevalent — around 40% of all HSP).
If the genetic testing does not establish an HSP mutation, then further consideration of the issue of diagnosis between the patient, the genetic counsellor and the medical practitioner will take place. Often families share in meeting the costs of mutation detection because the information is of benefit to all sections of the family. Screening of the rest of the family is a lot cheaper than initial testing.
What is screening and how is it different from testing?
Predictive testing / pre-symptomatic genetic testing / screening
This is the diagnosis for the rest of the family and for subsequent generations when a family gene has already been detected (see above). It is a more routine test and costs much less than the initial detection test.
With the knowledge of the family mutation, family members who may not be showing any physical signs of HSP can have their DNA screened for the presence or absence of the family mutation. As onset can be any time from childhood to 70 years, many will want to know what their future may hold. This test can prove the presence or absence of an HSP gene mutation in individual members of a family and can help to address people’s concern about whether they will develop symptoms or potentially pass on affected genes to their future children.
Testing and screening are always conducted in association with genetic counselling to help consider all the relevant information, make suitable choices and decisions for the individual and to deal with the ramifications of both good news and not so good news. This test requires a consent form signed by the patient in the case of those under 18 years old, 2 separate blood samples taken on separate occasions and genetic counselling.
My neurologist has already told me I have HSP. Why do I need more tests?
You would have had an assessment and diagnosis in the neurologist’s clinic that indicates you have HSP. The term HSP is representative of a number of conditions caused by one of numerous mutations in each of more than 50 different genes. Hence you have been advised of the disease group affecting you but not the specific gene mutation.
The gene test is carried out to:
- confirm the clinical test – some forms of multiple sclerosis, Charcot-Marie Tooth disease, motor neurone disease, some ataxias, and other diseases are very difficult to separate from each other, and from HSP by clinical diagnosis alone. Any doubts you may have some other ‘brain / legs disconnect’ disease is hopefully eliminated. Confirmation by genetic test is the only truly definitive diagnosis.
- determine the exact cause – the gene with the fault and the type of mutation.
- benefit relatives at risk by establishing the basis for existing and future family members who will then be able to screen for the presence or absence of the family mutation.
When I know my mutation, how is it going to help me?
You have this knowledge but it is also available (with your consent) to other family members who can consider, with the genetic counsellor, whether to screen for the presence or absence of the mutation (undertake predictive testing).
They can screen and, if they test positive, they can make more informed life choices including avoiding future children inheriting the mutation, preparing for the likelihood of onset with good management such as physical fitness, strength and flexibility, housing and potentially other issues.
If they test negative they have eliminated what may have been a deep-seated worry for themselves and their current and future children and their children. Decisions and choices can have much wider ramifications than just an individual’s medical case such as present and, as yet, unborn relatives at risk.
One of our members, Steve, writes:
“I have 3 daughters aged 20 to 29 showing no signs of HSP. I would love to be able to tell my kids no you don’t have HSP, but until I have any results from gene testing I cannot.
My sister, who also shows no signs of HSP, has always said no I do not want to know, but now, one of her daughters wants to know, so that she can consider children.
Once a gene has been identified then anyone in the family can be quickly and cheaply assessed. If the test is positive then family planning can be addressed. There are moral considerations that must be included but it is possible to eliminate HSP from future generations.”
How do I get started?
To be a candidate for testing, a neurologist must first diagnose that an individual may have, or be at risk of HSP. From there, it is on to a clinical genetics service. The services available across Australia and in New Zealand are listed on the Centre for Genetics website with contact and location details.
If your local public hospital doesn’t have a genetics service (some call it genetics counselling service) they will tell you the closest hospital that does. It is necessary to meet with a genetic counsellor prior to being tested.
How can my partner and I prevent our children inheriting HSP?
This is a subject that you and your partner should discuss with a genetic counsellor. The main issues are:
If the family mutation is not known then the partner concerned should undergo the mutation detection / discovery test.
If the family mutation is known and the partner has not been tested for the presence or absence of the family mutation then that should become the first step. A negative result is good news.
Once a mutation is known the couple can have discussions with a genetic counsellor. There are three options:
1. Pre-natal testing
A pre-requisite is the evidence of one parent with an HSP mutation that has been detected, referral from an appropriate doctor and a consent form signed by the mother-to-be undertaking the test. Genetic counselling applies.
Pre-natal testing involves taking a sample of the placenta at 11 or 12 weeks gestation, for DNA extraction and testing for the presence or absence of the known mutation.
If the test result is positive (mutation is present) the couple face a decision to terminate or not, made with the support of genetic counselling and medical advice.
2. Pre-implantation genetic diagnosis (PGD)
This method provides for only mutation free embryos being implanted to the womb of the mother to be in an IVF program.
A pre-requisite is evidence of one parent with an HSP mutation that has been detected, referral from an appropriate doctor and a consent form signed by both parents. Genetic counselling applies.
PGD involves an IVF clinic and assisted reproduction technology including stimulation of ovaries to enable the collection of a number of eggs that are fertilised in the laboratory with the prospective male parent’s sperm. The IVF Clinic takes an embryo biopsy of 4 to 6 cells on day 5 after fertilisation. Then gene tests are performed on each cell to identify embryos without the mutation present that can be used for implantation.
For some families at risk of passing on a genetic disorder to their children, PGD offers a more acceptable alternative to starting a pregnancy and later terminating. For couples with a moral or religious objection to pregnancy termination and who also are at risk of having a child with the genetic condition, this technique may provide the opportunity to have an unaffected child.
3. Proceed with neither
of the above interventions, but based on medical advice and genetic counselling, take either a calculated and considered risk of having children who may inherit the disease or choose not to have children.
What are the benefits of gene testing?
- It provides information for individuals so they can make life plans in the context of the new knowledge. With children, this predictive testing is not permitted unless they show signs of having the disease because the person must be old enough to deal with the implications of a result.
- Stopping the continuing inheritance of HSP in the family is possible with this genetic knowledge. Knowledge of the mutation causing the disorder allows couples to choose to enter an IVF programme including pre-implantation genetic diagnosis, i.e. implanting only embryos without the mutation, after embryos have been screened by gene testing. Approvals would have to be gained for inclusion of HSP in IVF programmes but the above is being done successfully with other conditions.
- Pre-natal testing would also be available once similar approvals have been gained for HSP.
- The peak onset age for HSP is in the twenties (ie. child bearing age) and it would be wise to determine the presence or absence of the gene mutation earlier rather than later because it can be passed on irrespective of the manifestation of the disease in the parent.
- Any future cure or therapy for HSP will almost certainly be mutation-specific. This means that knowledge of the causal mutation, which can only be obtained by gene testing, will be needed.
- Your basic right to know is being exercised.
Are there risks or issues associated with gene testing?
Having a small amount of blood drawn is a very low risk procedure most of us have experienced, however there are various important issues to consider in relation to genetic testing.
Genetic testing is so new that the legal, ethical and medical implications are still evolving and becoming clear. There are also important practical considerations such as privacy, insurance eligibility or employment that are worth exploring.
Medical professionals generally do not encourage testing people under the age of 18. This includes testing at-risk children or adolescents to determine whether they may eventually develop HSP. The exception is when symptoms that could be related to a hereditary disease such as HSP become evident.
People need to be able to deal with the implications of test results and there needs to be an appreciable benefit to the tested individual in having the knowledge that testing can provide. Even testing of adults needs to meet these criteria.
That’s why seeking guidance and support from a genetics counsellor is a great idea when considering testing. Counselling may be carried out by doctors who have had special training, or by genetic counsellors who are educated and certified as such.
The service is available at several major hospitals in Australia and New Zealand. Counsellors provide information about inheritance and the chances of having children affected by a particular inherited disease. They can also provide emotional support, make referrals to other resources and guide couples through family planning options and decisions.
What is a gene and what is a mutation?
A gene is a small region that can be located on the DNA. Genes are units of inheritance. Each contains a coding sequence that determines the protein the gene produces.
An error in the coding sequence of a particular gene results in the gene producing the wrong protein and the error is called a mutation ….. Over 50 HSP genes and more than 70 types of HSP have been identified, some with a large number of associated mutations. Gene tests are used to identify the mutation. Read more…