Understanding genetics in inherited MND

We spoke to people about their understanding of genetics in inherited MND. This section covers:

  • Finding information on the genetics of MND
  • Understanding genetics in inherited MND
  • Key definitions

Finding information on the genetics of MND

Inherited MND is complex, and research is ongoing to help improve understanding of the condition. Making sense of the genetics of MND may be confusing for families. People had different approaches to how much they wanted to know about gene variants associated with inherited MND and how they are passed on (inheritance), the likelihood of developing the disease if carrying a particular genetic variant (penetrance), gene repeat sequences in the context of genes like C9orf72, and factors that could influence the age where symptoms develop and contribute to the development of MND. The terms mentioned here can be found in the ‘key definitions’ section below.

Understanding these details was important and interesting for some people.

Finding out about the C9orf72 genetic variant in her family enabled Lillian to search for scientific papers. Learning as much as possible is “the way my mind works”.

For people who had a scientific background, reading scientific information and journal articles was a good way to get informed, and others spent time learning about these areas and becoming familiar with scientific jargon so they could understand. However, not everyone felt knowing this was necessary, or that it would change their experience of living with inherited MND in the family. Harriet said, “it’s not that important to me to know that detail. It doesn’t enhance my experience of all of this”. Some of the people we spoke to felt complex genetic information went “over my head”, and it was enough to know that other people understood it and were doing research on it.

People had different experiences of seeking information on inherited MND. People had sometimes been given information by healthcare professionals (including through genetic counselling), other family members, or had looked for reliable information online. Some families had been given misinformation in the past, such as being told that MND couldn’t be inherited, but this message had generally changed over the years. The information people want may evolve over time and with changing circumstances, along with people’s understandings and awareness.

Understanding genetics in inherited MND

People we spoke to generally understood that if a parent carries a dominant gene variant linked to inherited MND, each child has a 50% (or 1 in 2) chance of inheriting it. However, it could be difficult for people to make sense of the chance they could be affected.

For Kirsty, who didn’t know if her mum carried the C9orf72 genetic variant or not, understanding her own risk was more complicated.

Most were aware that there are different gene variants associated with inherited MND, though not everyone realised this at first; in other neurological conditions, like Huntington’s disease, there is just one gene linked to the disease.

Helen had never considered that there might be multiple genes which could cause MND. Finding out that her mother-law had the C9orf72 genetic variant “opened a whole world of questions”.

There was also some awareness that not all of the genes associated with inherited MND have been identified. Hugh had genetic testing after his MND diagnosis, which came back negative. He said, “I was one of the, whatever it is, 30%, 40% of people with familial MND who don’t have a known gene”. Where genetic testing came back positive, finding out the name of the gene variant in the family was significant new information for some people.

People highlighted that the same gene could cause such different symptoms, even within a family, which was hard to understand for some individuals. Learning that certain genetic variants, including C9orf72, can also cause other neurological symptoms like frontotemporal dementia (FTD) could be a lot to take on board. Karen said, “every case is different… In my family they both had limb onset… but that doesn’t necessarily mean that’s how it would impact on me if I was to get it… there is no way of knowing”.

David points out that there are many factors that influence how people are affected by MND, and it is important to treat everyone as an individual, with their own unique disease.

Several people talked about the issue of genetic variants of inherited MND seeming to ‘skip a generation’. This can appear to happen when a person passes on a gene variant to their child but doesn’t develop symptoms in their own natural lifetime, particularly if they die at a relatively young age.

This is also linked to the issue of penetrance (the terms mentioned here can be found in the ‘key definitions’ section below), as incomplete penetrance is another reason why the disease can appear to skip a generation. People we talked to generally understood that having the gene variant does not mean an individual will necessarily go on to develop MND, but people had been told or read different statistics about the chances. Although scientists generally agree that the chance of developing symptoms increases with age, and that different gene variants may have different penetrance, it is hard to give an exact figure on the increased likelihood that an individual who has inherited a gene variant associated with inherited MND will develop the disease in their lifetime. This is partly because there are other factors involved which are not completely understood (including protective genes), and other ‘triggering’ events that might have to happen during a person’s life. Adam asked his genetic counsellor for a figure on the chance he would be affected, which is where things got “cloudy”. Some people found these uncertainties gave them hope, but others found it hard to deal with, like Calum who said, “you could go your entire life thinking you have something when you might not get it, it’s just horrible not knowing”.

Hugh’s consultant told him that not everyone who carries a gene variant associated with MND will develop symptoms. This could be one reason why more family members haven’t been affected.

People were often interested in what may influence the age at which symptoms develop in people with inherited MND. Again, this is something that is not easy to predict for an individual. Some had been told that age of onset can follow a pattern in families, though it can also vary significantly between relatives. People generally imagined they would be affected at a similar age to parents and other family members. A few individuals were interested in how the number of ‘repeats’ in C9orf72 could influence the age symptoms develop. Lillian asked this question to researchers. She recalled, “there’s been papers saying in people with lower numbers of repeats, the onset is later in life… they just said that’s not absolutely proven”. Calum also had unanswered questions about the significance of the number of repeats. This is a subject of ongoing research.

Receiving his pre-symptomatic genetic test results, Calum had almost expected to be told “you’ve got it… we can see it in the microscope”, but he found the way the results were presented unclear.

People talked about other factors which could influence the development of MND. They sometimes questioned whether other genes, including from an unaffected parent, could have an influence. Others talked about potential lifestyle or environmental factors.

Family experiences can contribute to people’s understandings of how they or other relatives may be affected by inherited MND. Sometimes experiences of inherited MND in the family didn’t match what people knew about the disease. Robyn knew that men and women could be affected, but in her immediate family it was only males who had developed MND. Dani knew that the SOD1 gene could be passed on, but none of the next generation in her family had developed the disease to date. Sometimes, it was more or less than 50% of a generation who were affected, though people often realised there were more complex reasons behind this. Each child of a gene-carrier has a 50% chance of inheriting the genetic variant, in spite of how many siblings they have, but not everyone who carries a gene related to inherited MND will develop symptoms, although they can still pass this on to their own children.

Dani is one of sixteen siblings, and five have developed MND. She knows there is a 50% chance each sibling could be affected, and wonders if other siblings could be gene carriers.

Inheriting a genetic variant linked to inherited MND was seen as a matter of ‘luck’ or chance (the toss of a coin or roll of the dice) and individuals often pointed out that there was an equal chance of not inheriting the gene variant. Although some people emphasised that there was no way to know who would be affected, others talked about having a sense, hunch, or ‘gut feeling’ about whether they, or other relatives, would develop the disease. Such feelings were often based on physical and personality traits (being ‘like’ an affected parent or relative). These feelings and fears sometimes influenced people’s decisions to have pre-symptomatic genetic testing, or not to find out if they carried the gene variant in the family. Even though there was no “scientific reasoning” behind such feelings, they could be hard to put aside, an experience that has also been seen in research with families affected by Huntington’s disease.

Mary has always thought that she might develop MND, because she takes after her father and grandma in other ways.

Although research around inherited MND has developed rapidly, there is a lot that has yet to be discovered. People we spoke to had questions that had not been answered. Some individuals wondered whether other neurological conditions that had affected their family could be linked to inherited MND, or why gene variants like C9orf72 can cause FTD and MND. In other families, genetic testing had failed to identify a genetic cause of MND, in spite of multiple relatives being affected.

Key definitions

Gene variants linked to inherited MND

Scientists have discovered many genes associated with MND. The most studied genes are linked to inherited MND and significantly increase a person’s risk of developing the disease. These include C9orf72, SOD1, FUS and TARDBP. In people from a white European background, C9orf72 gene variants account for approximately 40% of cases of inherited MND, SOD1 for 20% and FUS and TARDBP for less than 5% each. In continental Asian populations, a higher proportion of inherited MND is caused by SOD1 gene variants and a much lower proportion is caused by C9orf72 gene variants. Scientists are continually discovering new genes associated with inherited MND and genes with changes that might increase an individual’s risk of developing MND. Other ‘variants of unknown significance’ (VUSs) may occur in genes associated with MND, which may or may not cause disease. Research in the future may help scientists to better understand their significance.


Inheritance refers to the way genetic characteristics are passed between parents and their children. We all carry two copies of each of the approximately 20,000 genes, one inherited from each parent. Most of the gene variants associated with inherited MND, including the most common variants mentioned above, are inherited in what is called a ‘dominant’ pattern. This means that only one changed copy of the gene is required to cause disease. An affected parent would have one normal copy of the gene and one copy with a change that could increase the risk of MND (pathogenic gene variant). Each of their children has a 50% chance of inheriting the gene variant that increases the risk of MND, and a 50% chance of inheriting the normal copy of the gene. Only one parent needs to carry one copy of a dominant gene variant linked to inherited MND for it to be potentially passed on to their children.


Penetrance refers to the proportion of people who carry a particular genetic variant who will develop symptoms of the associated condition in their lifetime. Where a gene variant is described as having incomplete penetrance, not everyone who carries this gene variant will develop the disease. This depends on a combination of environmental and other genetic factors. It is not currently possible to define exactly what these are and what they mean in terms of an individual’s risk.

Gene repeat sequences

The normal structure of the C9orf72 gene consists of a sequence of six bases (see ‘genes and gene variants’ above) with the code ‘CCGGGG’, repeated over and over again. Many other genes also contain repeat sequences, and repeating sequences may have important roles in how genes work. The number of repeats that each individual has on each of their copies of the gene can be variable, but when a repeat sequence expands beyond a certain size, it can then be associated with an increased risk of developing a disease like MND. Scientists study unaffected individuals to understand the range of repeat sizes which are ‘normal’. If a person has a higher than normal number of repeats, they are said to have a ‘repeat expansion’ which increases the chance of developing a certain disease, and they may pass this gene variant to their own children. In genes linked to inherited MND, like C9orf72, it is not completely understood how the number of repeats in the gene impacts a person’s chance of developing symptoms (including, for example, how the number of repeats could be linked to the age of onset). It is not always possible for a person to find out exactly how many repeats they carry. Sequences can be very long, and it is likely that the number of repeats can vary in different cells of the body and might change over time.

Please see the glossary section for more key terms.

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