by André Delacourte

General outline

Fatal familial Insomnia (FFI) is a Prion disease, a rare form of CJD.

Symptoms and course

Dementia associated with sleep disorders. FFI is reserved for patients manifesting prominent insomnia, generally in combination with dysautonomia, myoclonus, and eventual dementia, with the predominant pathologic changes lying within the thalami and a specific underlying mutation in PRNP.

Brain damage is confined to the thalamus, the area that is involved in relaying information to and from the brain and in controlling sleep-wake cycles.

Eventually FFI leads to a complete breakdown of the brain’s bodily functions, coma and death. The average age of onset is 50 years and the average duration of the disease is 12 months.

Genetics

Associated with the mutation D178N and the polymorphism 129M. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI.

Frequency

Unkown.

Diagnostic procedures

For people with symptoms of FFI, 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.

Post-mortem examination: Stripe-like deposition perpendicular to the surface in the molecular layer of the cerebellum, stained with antibodies against prion protein.

Available services

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 grahamsteel@hbsef.org

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

References

• Gambetti P, Hereditary Creutzfeldt-Jakob disease and fatal familial insomnia., Clin Lab Med 2003 Mar;23(1):43-64.
• Kovacs et al, Mutations of the rpion protein gene. Phenotypic spectrum. J. Neurol (2002) 249:1567-1582.