Overview of Fatal Familial Insomnia

A Condition That Causes Insomnia and Psychosis

In This Article

Table of Contents

Fatal familial insomnia is a hereditary sleep disorder that has affected about 100 families throughout the world on record, making it extremely uncommon. Insomnia is a decreased ability to fall asleep or stay asleep, and it does tend to run in families. Fatal familial insomnia, however, is characterized by a severely impaired inability to reach a state of deep sleep—it is accompanied by dementia, psychosis, abnormal movements, and alterations of physical functions such as heart rhythm. 

Diagnostic sleep studies may show an altered pattern and some brain imaging abnormalities may occur with the disease. A genetic test can verify the condition. While there is no effective treatment that can reverse or prevent fatal familial insomnia, ongoing research may point to some progress in the future. 

Fatal familial insomnia
Verywell / Jessica Olah  

Symptoms

The symptoms of fatal familial insomnia begin between the ages of 30 and 50, progressing rapidly within just a few years. Despite the name, insomnia may not be the first symptom of the disease. Neuropsychiatric issues, movement problems, and physiological effects can be the earliest symptoms as well.

The symptoms of fatal familial insomnia include:

  • Sleeping problems: Difficulty falling asleep and staying asleep are the hallmark features of this condition. This can result in daytime fatigue, irritability, and anxiety. Excessive physical movements or vocal noises may occur whenever a person with fatal familial insomnia falls asleep.
  • Behavioral symptoms: Most people with fatal familial insomnia develop anxiety or emotional instability. It also involves cognitive impairment (inability to make decisions and problem-solve) and forgetfulness. Eventually, skills of self-care are completely lost. Altered perceptions, such as seeing or hearing things that are not there, can occur. 
  • Movement disorder: Muscle twitching and erratic jerking movements often occur in fatal familial insomnia. Ataxia (balance and coordination problems), as well as uncoordinated eye movements, can develop. 
  • Autonomic dysfunction: The body regulates many physical functions through the autonomic nervous system, which is controlled by the brain. Autonomic dysregulation occurs with this condition, resulting in high blood pressure, hyperventilation (fast, shallow breathing), a rapid and irregular heart rhythm, increased sweating, and fevers or fluctuations of body temperature. 

The prognosis for fatal familial insomnia not good, with an average lifespan of only a few years after the onset of the initial symptoms.

Causes

This is usually a hereditary disease carried from parent to child through an autosomal dominant pattern. This means that a person who has one parent with the disease has a 50 percent chance of inheriting the genetic trait. 

Everyone who inherits the gene for fatal familial insomnia is expected to develop the disease.

It can occur sporadically as well, which means that a person can develop the condition without having inherited it, although sporadic cases are even less common than familial cases. 

Affected Areas of the Brain

Several regions of the brain are affected by fatal familial insomnia. The area most commonly affected is the thalamus, which moderates communication between different regions of the brain. It is believed that damage to the thalamus interferes with a person’s sleep-wake cycle, preventing progression past a sleep stage described as stage 1 sleep. This makes it impossible to achieve restful sleep.

Damage to the midbrain, a region of the brain stem, may cause movement problems and ataxia. Involvement of the cingulate cortex, an area near the middle of the cerebral cortex (the largest part of the brain, which controls planning and thinking), causes emotional, psychiatric, and cognitive (thinking) problems.

Fatal Familial Insomnia Is a Prion Disease

Fatal familial insomnia is a prion disease.

Sometimes prion diseases are called transmissible spongiform encephalopathies (TSEs) because some of them are contagious, but fatal familial insomnia is not contagious.

A prion is a protein called PrPc, and its function is not known. When it is folded in an abnormal shape, as in fatal familial insomnia, it is called PrPSc. These abnormal prions build up in several areas of the brain, and their presence is toxic, causing damage. Experts say that the toxic proteins may build up over years, and then suddenly cause symptoms when the brain’s functions are severely impaired. 

Chromosomal Mutation

The abnormally folded prions of fatal familial insomnia are caused by a genetic mutation (abnormality) in the PRNP gene that codes for prion protein. This gene is located on chromosome 20 in codons 178 and 129.

Diagnosis

This disease causes symptoms that are very noticeable. Initially, however, it can be confused with conditions such as dementia, movement disorders, or psychosis. Eventually, the unusual combination of symptoms along with a family history point to fatal familial insomnia. Sleep studies and imaging tests may support the diagnosis, while genetic testing can confirm it.

There are a number of different tests you may undergo during your evaluation.

Polysomnography (Sleep Study)

You may have a sleep study if you complain of sleeping problems. This is a non-invasive test that uses electrodes to measure electrical brain activity during sleep. The electrodes are held into place on the surface of the skull with adhesive. The brain’s electrical activity produces a pattern of brain waves that can be seen on a paper or a computer.

An unusual fluctuation between sleep stages may be seen in fatal familial insomnia. People with this condition tend to have a decrease in slow waves and sleep spindles, which are normally present during deep sleep. The brain waves may have an altered shape as well.

This study also measures breathing and muscle activity (of the arms and legs) during sleep. Normally, people have almost no muscle movement during the deep stages of sleep, but with fatal familial insomnia, a pattern described as agrypnia excitita is present. This pattern involves a lack of deep sleep, unusual muscle movements, and excessive sounds during sleep. These movements and sounds can also be seen with video monitoring.

Brain Imaging

A brain computerized tomography (CT) is not generally helpful in identifying fatal familial insomnia. It may show some abnormalities, including atrophy, which is shrinking of the brain. However, this finding is not specific for fatal familial insomnia and is found with many neurological conditions, especially dementia.

Brain MRI in fatal familial insomnia can show signs of disease in many brain regions. These are described as white matter leukoencephalopathy, which is not specific to fatal familial insomnia and can occur with other conditions as well, including vascular dementia and encephalopathy (brain inflammation or infection). 

Functional Brain Imaging

A type of brain imaging study called positron emission testing (PET) measures the activity of the brain. With fatal familial insomnia, PET can show evidence of decreased metabolism in the thalamus. However, this test is not standard and is not available in most hospitals. Furthermore, this abnormality may or may not be detected, and most health insurers do not typically cover PET scans. 

Treatment

There are a few things they can help alleviate some of the symptoms of this disorder, but there is no effective treatment that can reverse the disease or stop it from progressing. 

Medication to help reduce fevers and to maintain normal blood pressure, heart function and breathing may temporarily help stabilize vital signs and physical functions. Antipsychotics and medications used for movement disorders may be effective for a few days at a time. Vitamins B6, B12, iron, and folic acid may be used to help optimize well-being, and while is not clear whether or not they work, they don’t appear to be harmful.

Melatonin may help induce sleep, but it does not help in attaining deep sleep.

Typical strategies used for insomnia, such as sleeping pills and anti-anxiety medications, do not induce deep sleep because this disease causes damage to the mechanisms that allow deep sleep to occur in the brain.

Quinacrine, an anti-parasitic medication, was thought at one point to hold potential in treating fatal familial insomnia, but it was not effective and caused toxic side effects.

Ongoing Research 

Current research in Italy involves the use of an antibiotic, doxycycline, as a preventative treatment. Previously, it has been suggested that doxycycline may have anti-prion effects. Researchers have reported that at least 10 participants over the age of 42 who carry the mutation are enrolled in the study. All of the participants are receiving the medication and undergoing frequent assessment for early symptoms. Preliminary results are due to be reported in about 10 years. 

Antibodies against the abnormal prion have also been studied as a way to potentially immunize (vaccinate) against the disease. So far, this strategy has not been used in humans, and preliminary results in the laboratory setting are emerging.

A Word From Verywell 

Fatal familial insomnia is a devastating disease. Not only does it cause death, but in the years following diagnosis, life is very difficult for a person who has the disease as well as for loved ones. If you or a loved one is diagnosed with fatal familial insomnia, you owe it to yourself to seek emotional and psychological help and support as you cope with this overwhelming condition.

If you decide that you want to learn about ongoing clinical trials or if you are considering participating in a clinical trial yourself, be sure to discuss your interest with your doctor. You can also find information on government websites, patient support groups, and by contacting universities. 

 

Was this page helpful?

Article Sources

  • Burchell JT, Panegyres PK. Prion diseases: immunotargets and therapy. Immunotargets Ther. 2016 Jun 16;5:57-68. DOI: 10.2147/ITT.S64795.

  • Forloni G, Tettamanti M, Lucca U, Albanese Y, Quaglio E, Chiesa R, et al. Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases. Prion. 2015;9(2):75-9. DOI: 10.1080/19336896.2015.1027857.

  • Llorens F, Zarranz JJ, Fischer A, Zerr I, Ferrer I. Fatal Familial Insomnia: Clinical Aspects and Molecular Alterations. Curr Neurol Neurosci Rep. 2017 Apr;17(4):30. DOI: 10.1007/s11910-017-0743-0.

  • Lu T, Pan Y, Peng L, Qin F, Sun X, Lu Z, Qiu W. Fatal familial insomnia with abnormal signals on routine MRI: a case report and literature review. BMC Neurol. 2017 May 26;17(1):104. DOI: 10.1186/s12883-017-0886-2.

  • Tabaee Damavandi P, Dove MT, Pickersgill RW. A review of drug therapy for sporadic fatal insomnia. Prion. 2017 Sep 3;11(5):293-299. DOI: 10.1080/19336896.2017.1368937.