Fatal Familial Insomnia: All You Need To Know

Aside from being a mouthful, Fatal Familial Insomnia (FFI) is one of those diseases that you may only hear of, but never come across. It is a rare disorder. In the unlikely event of a suspicion that you or someone you know may have FFI, or you are simply a ‘Curious George’, this article explains the basics of this rare disease.

What Is FFI?

The name describes the disease. It is a disease that steals sleep (insomnia), runs in families (familial) and eventually leads to death (fatal). It starts with the infection of a part of the brain that regulates sleep.

The infection is not due to one of the regular bugs (bacteria, viruses and such); it’s caused by something called a Prion, which is what makes the disease so rare. It belongs to a class of diseases called Transmissible Spongiform Encephalopathy (TSE) or simply Prion disease.

There are two types of fatal insomnia – the Sporadic kind where the disease doesn’t run in families but spontaneously develops and the Familial kind which is our topic of discussion.

In the familial type, the disease is passed on from the parents to the kids through the genes in an Autosomal Dominant manner. This means that only one parent is needed to pass it on and there’s a 50% chance that parent will pass the defective gene to each child.


How Common Is FFI?

Generally, prion diseases are very rare. FFI is considered the rarest form of prion diseases. As of today, only about 40 families are known to have the FFI gene. Less than one in ten million people worldwide are affected. However, the actual occurrence is unknown because the disease is so rare and misdiagnosed. On the other hand, the sporadic form has 24 documented cases as of 2016.

What Causes FFI?

In the normal human body, there is a gene called the PRPN gene which contains the information for the prion protein PrPc.In FFI, this gene is mutated producing a defective prion protein. The defective protein has the capacity to cause serious neurological problems which is why the disease is fatal.

The malformed prion protein accumulates in the part of the brain called the thalamus which is where the sleep cycle is regulated. The thalamus is known as the relay center of the brain – where messages going from one part of our brain to another part pass through.

Other than the sleep cycle, the thalamus manages other major processes such as:

  • Information from sight, sound, and movement
  • Balance
  • Perception of pain
  • Learning
  • Speech
  • Memory
  • Personality

The mutated prion accumulating in the thalamus causes the nerve cells to degenerate, making the thalamus malfunction. When this happens, the thalamus cannot do its various roles, which are what we perceive as the symptoms of Fatal Familial Insomnia.   

What Are The Symptoms Of FFI?

The disease causes a progressive degeneration of the brain and nerves revealing itself over a period of time. It usually starts at middle–age (32–62 years) but may start earlier (as early as 18 years) or later (as late as 72 years).

The first sign may not be insomnia – it may be a rapidly progressive dementia. So the person might have the initial symptoms as forgetfulness and confusion.

The symptom of insomnia may come up as trouble falling asleep or trouble staying asleep (waking up multiple times).  Usually, the insomnia begins suddenly and rapidly worsens over a short period of time. At the onset of the insomnia, the little sleep gotten is punctuated by restless legs, tossing and turning.

 Other symptoms of FFI include

  • Weight loss
  • Loss of appetite
  • Too low body temperature (hypothermia)
  • Too high body temperature (hyperthermia)
  • Double vision (diplopia)
  • Phobias
  • Panic attacks
  • Hypertension
  • Episodes of hyperventilation
  • Episodes of profuse sweating
  • Erectile dysfunction
  • Behavior and mood changes

In the later stages of the disease, the person develops a total inability to sleep. The main part that is affected is the REM sleep which is where the brain resets and rejuvenates itself. Instead of sleeping, those affected might be in a state of stupor.


They may even act out their dreams. They may lose the ability to speak, develop abnormal movements (ataxia), hallucinations, muscle jerks (myoclonus) and become severely confused (delirium).

Eventually, their brain shuts down leading to a coma which ends up in their demise. Even though there are a lot of things that may be happening to the person, the disease course is very short. The time period of onset of symptoms till death averages about 1 year.

How Is FFI Diagnosed?

First of all, not a lot of doctors are aware of this illness. Like I mentioned before, it is a very rare disease so it doesn’t come up in the medical school curriculum. That being stated, the doctor has to have a very high level of suspicion for the disease which may be helped along with a family history of the disease.

The doctor would have to test for FFI if you have a parent with the disease. The first test to be done is the sleep study.

The sleep study, called a polysomnography, is where you are hooked up to lots of wires especially on your head and you are monitored as you sleep. There are the video monitor and the brain activity monitor which tells the sleep specialists what is happening as you sleep. Once a sleep disorder is diagnosed, further tests are done to rule out (or in) other possible causes of the sleep problem.

The next test to be done is the Positron Emission Tomography (PET) scan. This is like an ‘ultra-super-high-tech’ picture of the brain. It shows the activity of the different parts of the brain. If you have FFI, there would be decreased activity in the thalamus because the disease has destroyed it.

To confirm the diagnosis of FFI, a genetic test has to be done. Here, the scientists take a sample of your DNA (genetic code) and actually look for the defective gene. Once the gene is identified, the final word is out. A definitive diagnosis of FFI can then be made. 

Is There A Cure For FFI?

Unfortunately, there is no cure for FFI at this time. There is also no way of slowing down the progression of the disease. Treatment goals for those living with FFI are palliative based on current practices. This means that all doctors can do now is make the person as comfortable as possible by treating whatever symptoms they can.

However, there are foundations and researches dedicated to finding the cure. Hopefully, researchers will find one very soon.

What Are The Chances Of Survival?

The disease has no known survivors. Once the symptoms begin, death usually follows rapidly within 12–18 months. Sometimes it’s as short as 7 months. It can also be as long as 73 months. Until a cure is found and established, the prognosis of FFI is very poor.

What If FFI Runs In My Family?

If FFI runs in your family, then you may have witnessed the death of a loved one due to the disease. The first thing is for you to see your doctor who will refer you to a specialist with experience in handling this disease. You should be investigated to confirm you have the disease.

It also helps to join a support group (online or in-person) where you could speak with people who understand what you are going through.   

Is There Anyone Living With The Disease Now?

There is actually a family from Queensland, Australia who are living with the disease. They got it from their mother, who got it from her mother. This brother and sister watched their grandmother, mother, uncle and aunt pass away from the disease. Their response is to join forces with the researchers as test subjects to try to find a cure.

If you have been diagnosed with FFI your best response is to join forces with those working to find a cure. You can research the clinical trials which are ongoing and sign up as a volunteer. Working towards the goal of finding a cure is better for your overall health than sitting back to let the disease take its toll. It is possible to fight until you win!    

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Oyinkansola Kolawole, MD

Dr. Oyinkan Ogundimu is a graduate of medicine and surgery. She migrated to the United States to pursue her dream of caring for patients, her passion in life is to help people in all the ways she can including breaking down difficult to understand medical facts into simple and fun bits of information.
Oyinkansola Kolawole, MD