Human Prion Diseases
by André Delacourte and Clive Evers
Familial CJD is an inherited form of Creutzfeldt-Jakob disease, resulting from several types of mutations on prion gene.
There are fewer than 5 new cases of familial CJD occurring in the UK each year. Like other forms of CJD, familial CJD is characterised by dementia and neurological problems such as unsteadiness.
Symptoms and course
The symptoms and course of familial CJD will vary depending on the type of Prp mutation involved. There may even be a great variation in the symptoms within affected members of the same family.
However rapid progression to dementia and neurological symptoms are distinctive. Within weeks the patient may become unsteady on their feet, lacking in coordination and clumsy. Later symptoms may include blurred vision or even blindness, rigidity in the limbs, sudden jerky movements and incontinence. Difficulty in speaking, slurred speech and difficulty in swallowing may also occur.
Eventually the person will need full time care. Familial CJD often strikes at an earlier age than the sporadic form: the average age of onset is 52 compared to 65.
The course of the disease is often longer and the patient may survive for several years after the onset of symptoms.
Causes and risk factors
Human spongiform encephalopathy (TSE)
Familial autosomic by a range of mutations within the open reading frame of the prion protein gene (PRNP) on chromosome 20. We all inherit two copies of the PrP gene- one from our mother and one from our father.
Familial CJD, GSS and FFI are all inherited in an autosomal dominant fashion. This means you need to posses just one mutated copy of the PrP gene to develop the disease. A person carrying the mutated gene has a 50% chance of passing it on to each child. Since CJD does not usually strike until late in life, when people have usually had their children, the gene has persisted in the population.
Mutations in the PrP gene can now be detected via blood test. At risk family members who do not have symptoms therefore can opt to find out whether they carry the mutation. In most (but not all) cases a person is certain to develop the disease eventually if they carry the mutation.
It may also be possible to tell, from the form of the PrP gene carried, whether the person will have early or later onset disease. Undergoing Prp gene testing is a serious matter and should not be done without full consent of the person involved and full pre- and post-test support and counselling by specialist staff.
The results will have an impact on other family members and they should be involved in discussions. Antenatal testing where a foetus is at risk of carrying the mutation is also possible. This gives the couple a chance to opt for termination, and so avoids passing the disease on. However this also involves a difficult decision, for a child carrying a mutated PrP gene is likely to enjoy normal health for many years before the onset of the disease.
5 to 15% of all human spongiform encephalopathy.
For people with symptoms of familial CJD the investigations are the same as for any other prion disease. However, in addition, a simple blood test should confirm the presence of a PrP gene mutation. E.g. often but not always show characteristic changes. MRI will be done to eliminate other conditions such as a tumour. Blood and other biochemical tests are likely to be normal. The only definite diagnosis comes by post mortem. However in the case of inherited prion disease, the family history of neurological disease will be a very important pointer in the diagnosis.
National CJD Surveillance Unit Western General Hospital Crewe Road, Edinburgh EH4 2XU Scotland www.cjd.ed.ac.uk
In addition to surveillance and research they can organise intensive support for the person with CJD and their family.
Human BSE Foundation A charity set up by and for people who have been affected by vCJD. www.hbsef.org email@example.com
CJD Support Network Gillian Turner Birchwood, Heath Top, Ashley Heath Market Drayton Shropshire, TF9 4QR England www.cjdsupport.net
Prion Clinic Department of Neurology St Mary’s Hospital, Praed St. London, W2 1NY United Kingdom
- Kovacs et al, Mutations of the prion protein gene. Phenotypic spectrum. J. Neurol (2002) 249:1567-1582.
- CJD and prion disease: an introduction and explanation. Alzheimer’s Society CJD Support Network. December 1998.
- Will, RG et al A new variant of Creutzfeldt Jakob disease in the UK. Lancet 1996; 347; pp 921-925
- Douglas, MJ et al Patients with new variant CJD disease and their families:care and information needs. National CJD Surveillance Unit, Edinburgh, Feb 1999.
- Variant CJD:Alzheimer’s Society CJD Support Network. Information Sheet No 4. April 2001
Last Updated: vendredi 09 octobre 2009