Gene Testing Q & A

What’s new for people with, or at risk of, HSP?

Gene tests are now available Australia-wide. At the initiation of and funding by the HSPRF, the Northcott Neuroscience Lab of ANZAC Research Institute has developed gene tests for three major HSP genes (SPG4, SPG3A and SPG31). Mutations in one of these three genes cause about half the incidence of all HSP. In total there are currently 15 genes for which diagnostic tests are available worldwide out of more than 40 HSP genes that have been identified to date.

What kinds of tests are there?

There are 2 types of tests. The first is a test to discover the causal mutation of HSP in an individual. The second is called screening, and this means that people related to someone whose mutation is known are screened for the presence or absence of that mutation.

What is the testing process?

Procedural details for ordering the tests, and related information 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 test will detect the mutation and establish the aberrant coding sequence and type of mutation.

The clinical geneticist or neurologist will nominate the gene(s) for which a test is to be conducted based on the type of HSP the patient appears to have, family history and their knowledge of the prevalence of each gene (SPG4 is the most prevalent — around 40% of all HSP).

If the gene test is found to be negative for a given mutation, the doctor and patient will consider the diagnostic issue again and may nominate the next most likely gene and so on until the mutation is found. 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.

If the mutation is still not found from these tests, arrangements can be made via the testing laboratory for the sample to be sent to a research laboratory overseas that tests for mutations in rarer genes. This additional testing would be at no cost to the patient, but the test would have to be repeated in a testing laboratory (research labs can’t release individual results) for it to become clinically recognised. An additional cost would be incurred for this step.

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 been detected (see above). It is a more routine test and costs much less than the detection test.

With the knowledge of the family mutation, family members who are showing no 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 70years, 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, 2 separate blood samples taken on separate occasions and genetic counselling involvement.

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 30 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 MS appear just like HSP in the early stages. Any doubts you may have some other ‘brain / legs disconnect’ disease is eliminated.
  • 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. They are listed on the Centre for Genetics website and can be found, with phone numbers and addresses, at Genetic Counselling Services.

If your local public hospital don’t have a genetics service (some call it genetics counselling service) they will tell you the closest hospital that does. It is a good idea 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 most major hospitals in Australia. 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 40 HSP genes have been identified, some with a large number of mutations.  Gene tests are used to identify the mutation.