MND Associations, neurologists and genetic counsellors can help provide information and guidance on the genetics of MND.
About 10% of MND is ‘familial’ which means that there is or has been more than one affected person in a family.1 The remaining 90% of people with MND are the only affected person in their family and are said to have ‘sporadic’ MND.2
People with familial MND have the disorder because of a mutation in a gene.3 A mutation is an error in the genetic code which causes a gene to work abnormally. People with genetic mutations can pass these onto their children. If a person has an MND-related genetic mutation each of their children has a 50/50 chance of inheriting the MND-related genetic mutation.4
People who inherit an MND-related genetic mutation have a high, but as yet uncertain, chance of developing MND during their lifetime. However, not all people with an MND-related genetic mutation will develop MND. Other triggers may be needed for the disease to actually begin.
The age at which symptoms of MND appear in people with an MND-related genetic mutation varies greatly.5 It can be as early as the 20s and as late as the 80s. As well, the age of onset can vary considerably within a family, even though the mutation carried by family members is the same. The average age of onset of familial MND is around 45 years.6
Mutations in the genes that cause MND are also found in some people who have sporadic MND.7 The number of people with sporadic MND who also have an MND-related gene mutation is not known.
Most people with MND have the Amyotrophic Lateral Sclerosis (ALS) form of the disease. A gene defect has been identified in around 60-70% of ALS families, the main ones in Australia being C9orf72, SOD1, TARDBP, FUS, OPTN, and UBQLN2.8
|Year||Discovery||Relevant facts & insights|
|1993||The first genetic mutation related to MND was discovered in the superoxide dismutase 1 gene (SOD1).|
Evidence suggests 13.7% of familial MND is caused by mutations in the SOD1 gene.
|2008||Mutations in the TAR DNA binding protein (TDP-43) gene code were found to cause TDP–43 to become toxic, causing MND in a small percentage of MND families.|
Researchers are yet to find out how and why TDP-43 behaves abnormally to cause MND.
A gene mutation that causes a rare inherited form of MND, FUS (Fused in Sarcoma) was discovered.
Researchers have found that genetic mutations of FUS are a cause of MND for a small number of familial forms of MND and account for between 3%-5% of MND families.
The discovery of mutations in the C9orf72 gene was announced.
Mutations in the C9orf72 gene have since been found in about 40% of all families with familial MND. C9orf72 is also found in 5% to 10% of sporadic MND.
In recent times the pace of gene mutation discovery has accelerated due to advancements in technology and a concerted international collaborative approach with many mutations that affect small cohorts of people with MND now identified.
Although there are still some MND families in which the faulty gene has not yet been identified, C9orf72, SOD1 and other MND-related gene mutations discovered in recent years now account for 60.8% of all people with familial MND in Australia.9,10, 11
Other more recent gene discoveries include NEK1, C21orf2, TBK1 and TUBA4A.8
Researchers continue in their quest to find the mutations in other genes that cause familial MND in the families in which the genetic cause has yet to be identified. The rate of gene discovery in ALS is doubling every 4 years.12
Researchers are carrying out further studies to:
It is now possible to test for the presence of mutations in the SOD1, TDP43, FUS and C9orf72 and other recently identified genes in a person diagnosed with familial MND.13 Other family members can also be tested to determine if they have the same mutation that caused MND in their relative. For example, adult children or brothers and sisters of an affected person can be tested.
Unborn children can be tested to determine if they have inherited the mutation known in the family.
Pre-implantation genetic diagnosis (PGD), an advanced screening technique, can be used in conjunction with IVF to determine whether an embryo has inherited the familial MND gene. This screening technique has the potential to stop MND in future generations of that family.
Research will increase our understanding of the mechanism by which these mutations cause MND. Research may lead to treatments which can prevent or delay the onset of MND in someone with an MND-related genetic mutation. It is possible that research into MND caused by genetic mutations will also contribute to our understanding of the causes of other types of MND.
Some reasons people have given for wanting to know if they have an MND-related genetic mutation:
|Health and wellbeing||Family||Work and finances|
I am the sort of person who wants to know as much as possible about myself and my future and find it hard to live with uncertainty.
To enable me to plan my life.
To help with decisions about marriage and having a family.
To provide information of importance to my children.
If I do not have the gene, the information may help when I apply for jobs, life insurance, superannuation or when taking on long-term financial commitments.
Some reasons people have given for not wanting to know if they have an MND-related genetic mutation:
|Health and wellbeing||Family||Work and finances|
I can accept living with uncertainty and will be able to plan my life without knowledge of my genetic status.
I do not think I would cope with knowing that I have the gene and will have an increased risk of developing MND.
I am always free to change my mind and can take the test in the future if, for example, a treatment becomes available that can prevent MND.
|I would not change my plans regarding marriage and having a family, whatever the test result.|
Relationships with my family, friends and workmates may change if I am shown to have the gene.
|If I have a genetic mutation, the information may limit my life opportunities for example, in relation to career choices, life insurance, superannuation and financial matters.|