Fatal familial insomnia (FFI) is one of the rarest – the dominant gene that causes this type of dementia has been identified in only 28 families worldwide since its discovery in 1990 – dementias that have been identified so far.

Its first identifiable symptom occurs typically between the ages of 40 and 60 with a sudden increase in trouble falling asleep that quickly progresses to a greater inability to sleep and then just as quickly degenerates into total – and fatal – insomnia. The lifespan of a person once symptoms emerge is very short (around one year).

FFI is in a class of neurological diseases caused by prions ((Creutzfeldt-Jakob disease and its bovine equivalent, Mad Cow disease are other examples). Prions are abnormal pathogens that can be transmitted (in both humans and animals). They cause abnormal folding of prion proteins (normal cellular proteins that are found most abundantly in the brain). Prions are caused by a mutation of the PRNP gene on chromosome 20.

Prion diseases fall into three categories: sporadic, acquired, and genetic.

Sporadic prion diseases are random occurrences of these neurological diseases in people without any known risks or genetic mutations that could cause them. To date, the only prion disease that has sporadic incidences is Creutzfeldt-Jakob disease.

Acquired prion diseases occur because of exposure to the abnormal prion protein. These account for less than 1% of all prion diseases.

Genetic prion diseases are the most common form of prion diseases. FFI, along with Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker Syndrome (GSS), fall into this type of prion disease.

Since the mutated gene that causes FFI is a dominant gene, if only one parent has the mutated gene, the likelihood of his or her children having the mutated gene is 50%. If both parents have the mutated gene, then all their children will have it as well.

The areas of the brain most severely affected by FFI include the thalamus, the frontal cortex, and the central nervous system.

Because the first symptoms of FFI usually occur at or near the end of childbearing years, parents aren’t even aware that they are passing the defective gene on to their children. However, a diagnostic test has been developed to test for the mutated gene.

FFI has four discrete and degenerative stages.

In the first stage of FFI, the onset of sudden and unexplained persistent insomnia leads to panic attacks and irrational phobias. This stage lasts approximately four months.

During the second stage of FFI, continued sleep deprivation increases the number and severity of panic attacks and hallucinations become pervasive. This stage lasts approximately five months.

In the third stage of FFI, total insomnia occurs, resulting in rapid weight loss and very limited mental functioning. This stage can last for up to three months.

During the fourth and final stage of FFI, dementia and unresponsiveness occur. This stage can last up to six months.

There is no treatment or cure for FFI, and the mortality rate is 100%.

The Atlantic has an very interesting article on FFI that involves a 30-year-old woman whose mother died of FFI at age 52. The daughter is now working and hoping to find a way to intercept and neutralize the genetic mutation before she reaches the age where her symptoms begin. It’s a intriguing story, which I highly recommend.

For an in-depth look at the biology of prions, an excellent reference book is The Family That Couldn’t Sleep.