Fatal Familial Insomnia

What is fatal familial insomnia?

Fatal familial insomnia (FFI) is a rare genetic condition that affects your brain and central nervous system. It causes you to have trouble sleeping (insomnia), memory loss (dementia) and muscle twitching. FFI is degenerative, which means symptoms get more severe over time. Symptoms of the condition are life-threatening and there’s no cure. Studies are ongoing to find treatment options to reduce the progression of symptoms and extend the life of people diagnosed with this condition.

Who does fatal familial insomnia affect?

Fatal familial insomnia (FFI) affects people who inherit the gene from one of their biological parents. There’s usually a history of the condition affecting the family since only one copy of the mutated gene is enough to cause symptoms (autosomal dominant).

In extremely rare cases, FFI can occur in people who don’t have a history of the condition in their family. In these cases, the condition happens with a new genetic mutation (de novo).

How common is fatal familial insomnia?

Fatal familial insomnia (FFI) is very rare and affects an estimated 1 to 2 people out of every 1 million. Since FFI is genetic, there are approximately 50 to 70 families worldwide who carry the mutation that causes the condition.

How does fatal familial insomnia affect my body?

Fatal familial insomnia (FFI) targets your brain and central nervous system when proteins caused by a genetic mutation cluster on the part of your brain that controls body functions like sleep (thalamus). The most severe symptom is not being able to sleep (insomnia), which affects your mental capabilities and how your body functions. Symptoms are life-threatening and progressively get more severe over time.

What are the symptoms of fatal familial insomnia?

Symptoms of fatal familial insomnia include:

• Difficulty sleeping that gets worse over time (progressive insomnia).
• Nervous system overactivity including high blood pressure, a faster-than-normal heart rate and anxiety.
• Memory loss.
• Hallucinations or seeing or thinking that something’s there when it isn’t.
• Involuntary muscle twitching or jerking (myoclonus).

Symptoms of fatal familial insomnia (FFI) begin between the ages of 20 and 70. The average onset of symptoms is age 40.

Early symptoms of FFI can look similar to those of dementia and Alzheimer’s disease. If you experience symptoms, visit a healthcare provider to receive an accurate diagnosis. As the condition indicates in the name, symptoms can be life-threatening.

What causes fatal familial insomnia?

A mutation or change of the PRNP gene causes fatal familial insomnia (FFI). The PRNP gene is responsible for making the prion protein PrPC. Prion protein PrPC exists in your brain, specifically in the thalamus, which helps regulate body functions like sleep.

When there’s a mutation on the PRNP gene, the amino acids that build the PrPC proteins don’t have instructions to build the proteins correctly. This mutation is similar to folding your laundry. If you’re unsure how to fold a t-shirt, you might ball up the fabric and put it in a drawer. Over time, that drawer progressively becomes difficult to close because you collect several t-shirts that aren’t folded correctly. Misfolded t-shirts are PrPC proteins that collect on your brain and become toxic to the cells in your nervous system, which creates symptoms.

Can I inherit fatal familial insomnia?

Yes, you can inherit fatal familial insomnia (FFI). This genetic mutation passes in an autosomal dominant pattern, where only one parent needs to pass the affected gene for you to inherit the condition.

Rare cases of FFI occur sporadically, which means that there’s no history of the condition in your family and the gene is a new mutation. You can pass the new mutation onto your future children.

If you plan on becoming pregnant and want to understand your risk of having a child with a genetic condition, talk to your healthcare provider about genetic testing.

What is the cause of death among people diagnosed with fatal familial insomnia?

The cause of death for people diagnosed with fatal familial insomnia is damage to the brain and nervous system. This damage, caused by prion proteins accumulating in the thalamus, creates symptoms of insomnia and mental deterioration.

Why is sleep important?

Sleep plays an important role in keeping you healthy. Sleeping improves your mental and physical health. When you’re asleep, your brain works with your body to support itself so you feel awake and energized in the morning. If you don’t get enough sleep, your brain loses the ability to recharge and it affects your ability to think and function normally. If your brain isn’t functioning at 100%, it consequently affects how your body feels and functions.

People diagnosed with fatal familial insomnia are unable to sleep, which disrupts how their brain functions. This creates negative side effects that challenge their overall well-being, causing life-threatening symptoms.

How is fatal familial insomnia diagnosed?

Your healthcare provider will diagnose fatal familial insomnia (FFI) after reviewing your symptoms and offering tests to confirm the diagnosis. Tests could include:

• Polysomnography: Sleep test to detect sleep pattern abnormalities.
• Electroencephalogram (EEG): Test to measure electrical activity in your brain.
• Cerebrospinal Fluid (CSF) analysis: This test examines cerebrospinal fluid (fluid in your brain and spinal cord) to identify conditions that affect the brain and spinal cord.
• Genetic testing to identify the gene responsible for symptoms.
• Imaging tests: MRI, CT scan or PET scan.
• Labs like a complete blood count (CBC), liver function test and blood cultures.

How is fatal familial insomnia treated?

Treatment for fatal familial insomnia (FFI) focuses on relieving symptoms and making you more comfortable. Some treatment options, especially medicines, may work temporarily to relieve symptoms. There’s no cure for FFI.

Treatment could include:

• Taking medicine to activate deep sleep (gamma-hydroxybutyrate, phenothiazines).
• Taking clonazepam to treat muscle spasms.
• Taking vitamins (B6, B12, iron, folic acid).
• Changing dosage or stopping medicines that make symptoms worse.
• Psychosocial therapy.
• Hospice care.

Studies are ongoing to find new treatment options for people diagnosed with FFI. One study found that the antibiotic doxycycline showed success in prolonging the life of people diagnosed with FFI.

What medicines don’t work to treat fatal familial insomnia?

Some medicines to help you fall asleep, like melatonin supplements, only temporarily work to treat fatal familial insomnia (FFI). Studies found that sedatives (barbiturates or benzodiazepines) are an ineffective treatment.

How can I prevent fatal familial insomnia?

You can’t prevent fatal familial insomnia because it’s caused by a genetic mutation that sometimes happens sporadically, without a history of the condition in your family.

What can I expect if I have fatal familial insomnia?

There’s no cure for fatal familial insomnia (FFI). After a diagnosis, treatment is symptomatic to make you feel more comfortable, with palliative care. The life expectancy for a person diagnosed with FFI is poor — especially after symptoms start, where the life expectancy ranges from a few months to a couple of years. The condition is progressive, which means it gets worse with time.

Families are encouraged to participate in therapy to discuss care options not only for the person diagnosed with the condition but to emotionally support themselves and prepare for the sudden loss of a loved one.

When should I see my healthcare provider?

You should visit your healthcare provider if you have trouble sleeping, especially if you experience sleepiness during the daytime that doesn’t get better. Symptoms of fatal familial insomnia relate to those of dementia and Alzheimer’s disease, so if you have memory loss and loss of motor skills combined with difficulty sleeping, visit your provider.

What questions should I ask my doctor?

• Do you recommend hospice care at this stage of the diagnosis?
• How severe are the symptoms?
• Are there any treatment options that’ll help relieve symptoms?

A note from Cleveland Clinic

A diagnosis of fatal familial insomnia can be devastating, especially when symptoms start and progressively get worse over a few months. Surround yourself with support from your healthcare providers, along with your family, friends and mental health professionals to make your diagnosis more comfortable. Palliative care and treatment options can temporarily alleviate your symptoms. Studies are ongoing to find more effective treatment options for people diagnosed with this condition to prolong life expectancy.