MND is a general term applying to progressive, degenerative disorders affecting the motor neurones. It is also known as Amyotrophic Lateral Sclerosis (ALS) in Europe and the UK, but in Australia, the term MND is more often used. Motor neurones carry signals from the brain to the muscles. In people with motor neurone disease, the motor neurones deteriorate and can no longer carry these signals. This is a gradual process, which causes muscles to waste away. Some people carry genetic faults that predispose them to this motor neurone deterioration, and these people are at increased risk of developing MND over their lifetime.

Families with a gene fault or a strong family history of MND are known to have familial MND (also known as "FALS"). About 10% of all people with MND will have familial MND, meaning the risk can be inherited. The remaining 90% of people with MND have ‘sporadic MND’, meaning that only one person in the family has the disease. Age of onset of familial MND varies from family to family and depends on the gene fault involved. Still, not everyone with a faulty gene will go on to develop MND, and it is important to know that we currently are unable to predict if, when and how MND may affect someone with a faulty MND gene.

A condition called frontotemporal dementia (FTD) can also be caused by some gene faults that can also cause MND. FTD is a form of dementia and associated with changes in behaviour, language and personality. In these families, some family members may have had MND, FTD or a combination of both conditions. MND Australia has more information about MND and FTD

Genetic testing in family members can allow each person to know whether they have inherited the same faulty MND gene, and if they are at increased risk of developing disease. Not everyone with a faulty gene will go on to develop MND. However, the chance of developing MND is much higher for those carrying MND genes. This chance depends on the faulty gene involved, and sometimes even the family specific mutation. At this time, we currently are unable to predict if, when and how MND may affect someone with a faulty MND gene.

• Not all the gene faults that cause MND are known. To date, several genes that are associated with MND risk have been identified. The most commonly tested MND genes are: SOD1 and C9orf72. The C9orf72 gene is thought to cause around 40% of familial MND in Australia. Having this mutation may result in people developing MND, frontotemporal dementia (FTD) or a combination of both MND and FTD. The SOD1 gene is responsible for a further 20% of cases of familial MND.
• Around 40% of people with familial MND, identified by a strong family history of the disease, do not carry an identified gene fault.
• Occasionally, genetic testing may find that someone thought to have "sporadic MND" has "familial MND" because they carry an identified gene mutation.
• If you have a known genetic fault for MND in your family and find out through testing that you don’t have it, your risk of disease is the same as anyone else the general population of developing sporadic MND.

Testing is usually done with a simple blood test. Testing for MND genes is optional, and can only be done with your signed consent. There are two types of genetic testing that can be performed.

1. Diagnostic genetic testing: This is also known as ‘mutation search genetic testing’. This is a test performed when no gene fault has previously been identified in the family. It is usually performed on a person with MND and may test a single MND gene, or multiple MND genes. Before testing, genetic counselling is available to help you decide if proceeding with testing is right for you.

You could also elect to provide a blood sample and store it until you or your family have decided to proceed with testing. This can be particularly important if you or other family members felt the timing was not right to undergo genetic testing.

2. Predictive genetic testing: This test is available to relatives once an MND gene fault has been identified in the family. The test is known as a 'predictive' test as it will inform you whether you do (or don't) carry the family faulty gene, and therefore whether you do (or don't) have an increased risk of MND over your lifetime. Before testing, genetic counselling is required to help you decide if proceeding with testing is right for you. This is a requirement even if you are sure that you wish to have the testing. A referral from a GP is enough to book an appointment at a testing clinic.

It is also possible that you may be offered ‘confirmatory genetic testing’. This is a test that is done in a family member to confirm whether they carry the gene fault in the family. The test is considered ‘confirmatory’ rather than ‘predictive’ if someone already has symptoms of MND or FTD and therefore are likely to carry the same gene change.

The decision to have genetic testing is completely voluntary. The results are completely confidential, and can’t be shared without your express consent. Even if you choose to share your results with researchers, they will remain anonymous.

Reproductive genetic testing is also possible and is further detailed in "How does genetic testing help me decide about family planning".

Many families find that each member has a different attitude towards having genetic testing, and knowing the results of their test. While some family members may be supportive of your decision to have or to decline testing, others may not. It is your choice who you discuss your decision with.

Your GP can refer you to health professionals who specialise in genetic testing services. Genetic counsellors will be able to provide you with expert information about genetic testing for MND that is specific to your family situation. They also offer support through your decision-making, and as you learn about your results, and what they mean for you. There are many genetic counselling clinics across Australia. The Human Genetics Society of Australia provides a list of public and private options for genetic counselling to help you find a local genetics counselling service.

Other professionals who can provide information include MND doctors and health professionals, advisors from your local MND associations, and your GP. For more information about familial MND, you can also contact the MND team who has treated the person with MND in your family.

MND Australia also provides information and advice for MND patients, carers and family. A fact sheet on genetic testing for familial MND can be found at MND Australia.

(Adapted from https://ghr.nlm.nih.gov/primer/consult/expectations)

During a genetic counselling appointment, the genetic counsellor or other health professional provides information, offers support, and addresses a patient’s specific questions and concerns about a family history of disease, a specific genetic condition and/or genetic testing.

During a consultation, a genetics professional will:

• Review your personal health history and family history of MND and/or FTD.
• Interpret and communicate complex medical information in a meaningful and non-judgmental way. This may include information about a diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment.
• Help each person make informed, independent decisions about their health care and reproductive options.
• Respect each person’s individual beliefs, traditions, and feelings.

A genetics professional will NOT:

• Tell a person which decision to make.
• Advise a couple not to have children.
• Recommend that a woman continue or end a pregnancy.
• Tell someone whether to undergo testing for a genetic disorder.

Family planning for people with an inherited condition has always been a complex issue. To assist their decision-making, some familial MND family members decide to have genetic testing in conjunction with In Vitro Fertilisation (IVF). Some IVF clinics can test embryos before they are implanted to determine whether they carry an MND gene.

Pre-implantation genetic diagnosis (PGD) involves screening IVF-generated embryos for genetic conditions prior to embryo transfer. Parents can then choose how they proceed with implantation.

IVF clinics can provide information on pre-implantation genetic diagnosis, and on where this specialist screening is available. They can also provide information on the associated costs and the Medicare rebates available.

As with other inherited conditions, genetic testing can also be conducted after a pregnancy has occurred.

Once a gene mutation has been identified in a family, couples who are planning a family can consider options that may help to prevent a gene mutation being passed on:

1. Do nothing. If a couple conceives naturally and chooses not to undergo testing of the pregnancy, there would be up to a 1 in 2 chance that each pregnancy will have inherited the faulty MND gene.
2. Do nothing, conceive naturally and undergo prenatal diagnosis. From approximately 10.5 weeks, couples can elect to have genetic testing on the pregnancy using chorionic villus sampling (CVS). CVS involves using a needle to take a sample of the placental cells. These cells contain DNA from the pregnancy and can be used to test if the faulty gene is present. Amniocentesis is another needle test that is available from approximately 16 weeks. CVS has a 1% (or 1 in 100) risk of miscarriage, and amniocentesis has a 0.5% (1 in 200) risk. Based on the information from the needle testing or ultrasounds, couples can then elect to stop the pregnancy if the faulty gene is confirmed.
3. Undergo IVF with a plan to do pre-implantation genetic diagnosis (PGD). PGD is a process in which embryos are tested prior to implantation into the womb and only those embryos that are not affected are implanted. The benefits of PGD are that couples can prevent passing on the condition to children, and not be faced with the option of termination of pregnancy. Unfortunately, as with all IVF procedures, there is no guarantee of a healthy pregnancy and PGD can be costly.
4. Other options include use of donor egg, sperm or embryo, adoption and choosing not to have children.
5. There are also options available if a person decides they do not want to undergo predictive testing for themselves. This is known as exclusion testing and can be performed with PGD, and sometimes, with prenatal diagnosis.

Decisions about family planning can be complex. Your genetic counsellor could further discuss these aspects with you, or you could consider referral to an IVF clinic.

The testing must be voluntary, and the person undertaking must be able to give informed consent and be over 18 years of age. If you choose to undergo genetic testing, the results of your test will not be released to others without your formal consent.

Testing costs vary considerably, depending on the type of testing being conducted, and the type of genetics service you access. Many public genetic testing services may provide subsidised or free testing for MND-related genes, especially if you are from a familial MND family. Other services may be expensive, so it is wise to ask about costs beforehand.