In inherited prion disease, also known as familial prion disease, a genetic mutation (fault in the gene that codes for the prion protein) causes abnormal prion proteins to be produced in the body, which themselves are predisposed to undergo the change in shape that leads to production of rogue proteins.
The disease runs in families in what is known as an “autosomal dominant” pattern of inheritance. That is, each child who has a parent with inherited prion disease has a 50% chance of having the faulty gene. Those individuals, who do not inherit the mutation and are therefore unaffected, cannot pass the disease on to any of their children. This means that in any affected family it is possible that some; none or all of the offspring will inherit the illness.
Sometimes the disease will skip a generation. This can occur because someone with a mutation may die of an unrelated cause before the prion disease has developed, but after passing on the gene to their children. There is often considerable variation in the age of onset in different members of the same family and in some the onset may be so late that dying from another cause (unrelated to prion disease) is quite likely. It is possible that some individuals with certain mutations may not develop the disease at all even if they live to an advanced age.
The familial forms of the disease account for about 15% of human prion disease. A person with the faulty gene is most likely to develop symptoms between the ages of 30-60 and the duration of illness is approximately 2-5 years. However illnesses have been known to develop earlier or later in life and symptoms may last from several months to 20 years.
To date over 30 different mutations have been identified in the prion gene. Traditionally these have been named according to the doctors that first described the condition, as either inherited Creutzfeldt-Jakob Disease (CJD), Gerstmann-Straussler-Scheinker Disease (GSS) or Fatal Familial Insomnia (FFI).
Depending on which mutation has been inherited, there will be variation in the age of onset and duration of disease. To some extent each different fault will also produce a slightly different set of symptoms which characterises the illness in a specific way. However, even within the same family, all of whom would have the same genetic fault, the presentation of the illness may be very different.
Features of Inherited Prion Disease
Common features do exist between all three forms of the familial disease and for this reason these illnesses have more recently been classified as inherited prion disease, followed by the number associated with the particular mutation. For example, P102L, 6-OPRI or E200K. Initial signs are usually fairly subtle; fatigue, insomnia, weight loss, headaches and ill-defined pain sensations are sometimes the first signs of illness. Individuals may complain of altered sensations, for example, numbness, tingling or pain in the arms or legs. Refer to the signs and symptoms page for further information.
When prion disease is suspected a blood sample is taken to look for a genetic fault/mutation in the prion protein gene. Because of the potential implications that the test may have, not only for the person being tested but also for any siblings, children and other family members, the doctor needs to obtain consent for this blood test.
It is possible to carry out the same test on adults who have no symptoms of the illness, but who have a parent or other close relative that has died of inherited prion disease. This test can determine whether a person is likely to develop the disease when they are older or not. The issues around genetic testing are complex and the decision of whether or not to proceed with the test is a difficult one. Genetic counselling, which may occur over a several month period, is therefore carried out before any blood sample is taken. The decision to have the blood test should be a personal one, without pressure from other family members or health professionals, and people must be over 18 years of age.
If you wish to discuss testing of a foetus in the womb please contact us for advice, if possible when considering pregnancy.