Fatal familial insomnia

What causes fatal familial insomnia?

Fatal familial insomnia (FFI) is a very rare form of genetic prion disease. In almost every case it is caused by a very specific mutation in the PRNP gene. This mutation causes the prion protein (PrP) that is made from this gene to be a different shape (fold incorrectly). Since the protein has a different shape, it cannot work correctly.

The abnormally shaped PrP (prion protein) causes changes in the thalamus including the progressive loss of neurons (nerve cells). The thalamus relays messages between different parts of the brain. It manages our sleep/wake cycle; the flow of visual, auditory, and motor information; our sense of balance; how we experience pain; aspects of learning, memory, speech and understanding language; and even emotional experiences, expression, and our personalities. Losing neurons in the thalamus causes many of the symptoms of FFI because the thalamus can no longer do all of its jobs well.

Although the main target of FFI is the thalamus, other parts of the brain are affected as well including the inferior olives. The inferior olives are part of the medulla oblongata and are important for coordinating our movements (motor control). Losing neurons in the inferior olives can make it harder for a person to control their movements as seen in later stages of FFI. Medical researchers are still working to understand how the abnormally folded PrP causes the progressive changes in the thalamus and other affected brain areas.

In very rare cases of FFI, the cause is sporadic, meaning there is not a change in the PRNP gene. As of 2016, there have only been 24 reported cases of sporadic FFI. Sporadic FFI occurs when some of a person's normal PrP (prion protein) spontaneously changes into the abnormal shape which causes FFI, and then somehow changes the shape of PrP in other neurons in a chain reaction.

Last updated on 05-01-20

How is fatal familial insomnia diagnosed?

The diagnosis of fatal familial insomnia (FFI) is first suggested by rapidly progressive cognitive impairment (dementia) along with behavior or mood changes, ataxia and sleep disturbances. Further diagnosis will include a sleep study and possibly a PET scan to confirm thalamic hypometabolism (meaning the thalamus in the brain is less active than it should be). The recommended PET scan is the fluorodeoxyglucose positron emission tomography (FDG-PET).

Genetic testing can confirm the diagnosis, but in the United States is only available if the person meets one of the following three criteria:

  • Family history of FFI
  • Abnormal sleep study or PET scan (consistent with strong suspicion of FFI)
  • Diagnosis of FFI (usually through a combination of sleep study results and PET scan results)

Carrier testing for at-risk relatives and prenatal testing are possible for families with a confirmed diagnosis of FFI.

Last updated on 05-01-20

How is fatal familial insomnia inherited?

In most cases, a person with fatal familial insomnia (FFI) has inherited the genetic change from a parent with FFI. In order to have FFI, a person only needs one copy of their PRNP gene to carry the specific genetic change (mutation) that causes FFI. In other words, a person only needs to inherit the genetic change from one parent. In genetic terms, this is called autosomal dominant inheritance. In rare cases, FFI may result from a new (de novo) change in the PRNP gene, however it is not known how often a new mutation is the cause of FFI. New mutations can happen during the making of the egg or the sperm.

A person that has the genetic change that causes FFI has a 50% chance with each pregnancy of passing along the changed gene to his or her child.

In the rare sporadic cases of FFI, the disease is not inherited from either parent and cannot be passed down to their children.

Last updated on 05-01-20

How is the sleep study of a person with fatal familial insomnia different from another person with insomnia?

The sleep study EEG of a person who has insomnia but not fatal familial insomnia (FFI) shows mainly delta wave activity (high-amplitude slow waves of sleep stage 3 or deep sleep) and episodes of “micro-sleep”. There are also brief bursts of K-complexes (large waves in sleep stage 2 or light sleep) and sleep spindles (small bursts of activity in sleep stage 2). Insomnia with this pattern is associated with perceiving something that isn't there (disturbed perception), moments of not being aware of self or surroundings (lapses of consciousness), and quickly changing and often extreme behavior or emotions (erratic behavior).

In people with FFI, sleep study EEGs contain a mixture of rhythms that are neither typical of wake nor of light sleep, and may be called “subwakefulness.” There is a clear absence of sleep spindles and K-complexes. Total sleep time is shorter and the sleep study shows only slow activity or desynchronization without rapid eye movements (REM).

Last updated on 05-01-20

How can I learn more about the normal stages of sleep?

You can lean more about sleep stages and the importance of sleep at the following resources:

Last updated on 05-01-20

What is the long-term outlook for people with fatal familial insomnia?

Presently, after symptoms of fatal familial insomnia (FFI) begin, the disease usually causes death within 12 to 18 months, with a range of a few months to several years. As research continues however, it is hoped a treatment or even a cure will be developed that will dramatically change the outlook for people who have FFI.

Last updated on 05-01-20

How might fatal familial insomnia be treated?

There is currently no cure for fatal familial insomnia (FFI) or treatment that can slow the disease progression. The management goal is to ease symptoms and keep the person with FFI as comfortable as possible. However research is ongoing and a number of potential treatments are being developed.

As of 2016, a number of treatments have had some success in slowing disease progression in animal models, including pentosan polysulfate, quinacrine (mepacrine), and amphotericin B. Sadly, the results have been less clear in clinical trials in humans. In Italy, a clinical trial trying to prevent symptoms in people known to have the genetic changes for FFI but have not yet developed symptoms is underway using doxyclycline. Most promisingly, several forms of immunotherapy have reported success. The three main research areas focus on antibody vaccines, dendritic cell vaccines, and adoptive transfer of physiological prion protein-specific CD4+ T-lymphocytes. More research is being done to study how well these treatments work (effectiveness) and if the treatments are safe, but medical researchers believe that these or similar immunotherapies may offer hope for those with FFI in the future.

Last updated on 05-01-20

Name: Creutzfeldt-Jakob Disease Foundation, Inc 3610 W. Market St. Suite 110
Fiarlawn, OH, 44333, United States
Toll Free: 1-800-659-1991 Fax : +1-234-466-7077 Email: help@cjdfoundation.org Url: https://cjdfoundation.org/
Name: Cure FFI.org Email: http://www.cureffi.org/contact/ Url: http://www.cureffi.org

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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