Dr Cooper gave an overview of the genetics service offered at Birmingham Women's and Children's Hospital, although much of what she said is good relevant information. She began outlining that one in 17 of the population are likely to have a rare condition in their lifetime, and genetic testing can help to identify the cause and progression of such diseases.
There are four main aspects of the care that they give:
1) Giving information on what genetic testing is - how it can (with a definitive result) be used to guide treatment and give an assessment on potential outlooks on life, and can give information on if things are/can be passed to children and the level of risks for different aspects and provide information for the family.
2) Outlining the different choices available - there are tests for individuals, and tests can be done on children and during pregnancy.
3) Providing support for the while family - the results of a test can affect more than just the person being tested.
4) Help families make the choices that are right for them.
In the wider sense diagnoses can be made in a number of different ways. The persons family tree can be examined, there can be a number of physical examinations or investigations, and sometimes there is a genetic test available.
There are three types of genetic inheritance, and there are examples in HSP of all three types. Each gene that person has is a pair of genes, one from their father and one from their mother.
If a condition is 'dominant' then the gene for that condition needs only to be in one of those pairs for the person to have that condition. (SPG4 has dominant inheritance). With dominant conditions there are no skipped generation and each child has a 50/50 chance of inheriting from their affected parent.
If a condition is recessive, then the person needs to have inherited the gene from both parents. (SPG11 has recessive inheritance). If a person has one copy of the recessive gene then they are a 'carrier' of the condition but are not affected by it. Recessive conditions can skip generations as people can be carriers. If both parents are carriers then the chance of a child being affected by the condition is 1 in 4.
Lastly X-linked inheritance where the gene for the condition is on the X chromosome. These generally affects males as they only have one copy of the X gene, being XY). Females are XX, and are usually unaffected by the condition but can carry it. (SPG1 has X-linked inheritance).
Further to inheriting genes from our parents there will also be some genetic changes within us. Dr Cooper said that each person has around 60 genetic changes which are not in either parent. Such changes could lead to HSP with any form of inheritance.
Dr Cooper then went on to talk about diagnostic testing. This can be used for a person affected by a condition. The testing can firstly identify what the condition is, and then hat type it is. Predictive testing can similarly be undertaken for unaffected relatives. Having a test can help with planning, career choices, life decisions and that kind of thing.
With predictive testing there will always be a look at personal history. This will help understand the personal circumstances for the person and level of support that they would have. One of the biggest factors is that having a test changes perspectives - you move from "might have" a condition to "will have" a condition. Part of the personal history is getting a feel for how this might affect someone psychologically. Having a result can be beneficial in terms of planning for the future, but could also have a disadvantage in that you may have to declare that you have a condition when applying for a mortgage, for example. She noted that a clinical examination is always a snapshot of a person, it cannot tell you how you will be in the future.
Dr Cooper described two different types of genetic testing. Until relatively recently genetic tests were done using "Sanger Sequencing" which looks at one gene at a time. Now such test are done with New Generation Sequencing (NGS), where a panel of different genes are looked at simultaneously. Gene panels tend to have ~40 different genes in them.
One issue with panel tests is that interpeting the results can be difficult to do. Some of the results back are not clear. Other results may come back showing changes, but it is not always clear that those changes are giving rise to the effects being observed. Some people are affected by more than one rare condition, and it may be difficult to identify what is going on from panel test result, especially if some of those conditions are similar. The age of onset and rate of progression of HSP have influences from other factors. Some of these factors will be genetic and others will be environmental.
Dr Cooper described genetic changes as being like a key. The genetic change can happen at any place in the gene and the effect of the change depends on where it happens. If we liken a gene to a key, then if the change occurs in the part of the key which you hold then the key will still open the lock perfectly. Some change may be small, and that might be like a slightly wrong key which you can get to open the lock by giving it a bit of a wiggle - and that all might be OK. When the change is bigger or occurs in the blade of the key then the lock may not be operable with that key.
If you are in the UK and do not have a genetic test result for HSP then you may be eligible for the 100,000 Genome Project. Talk to your neurologist!
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