Fatal familial insomnia

Información en español Title

Other Names:

Familial fatal insomnia; Insomnia familial fatal

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Fatal familial insomnia (FFI) is an inherited prion disease that mainly affects the thalamus. ^[1]^[2]^[3]^[4] The thalamus is the part of the brain that controls the sleep-wake cycle, but is also known as the "relay center" of the brain because it helps the different parts of the brain communicate with each other.^[2]^[5] Like all prion diseases, FFI is a progressive neurodegenerative disease, which means over time there are fewer neurons (nerve cells). Loss of neurons in the thalamus, as well as other mechanisms not yet fully understood, cause the symptoms of FFI.^[3]^[4]^[6]

The first symptoms of FFI usually begin in mid-life and may include progressive insomnia, weight loss, lack of appetite, too high or too low body temperature, and rapidly progressive dementia. Almost all cases of FFI are caused by certain changes (mutations) in the PRNP gene and are inherited in an autosomal dominant manner.^[1]^[2]^[3]^[4] There are a very small number of reported sporadic cases of FFI.^[7] There is currently no effective treatment for FFI, but research for a treatment and cure is ongoing.^[2]^[4]^[7]^[8] Death usually occurs within 12-18 months of the first symptoms.^[2]^[9]

Last updated: 12/2/2016

Symptoms Symptoms

The first symptoms of fatal familial insomnia (FFI) usually begin between the ages of 32 and 62 (mean average 51 years), but have been reported to begin as early as 18 to as late as 72.^[2]^[10] It is important to note that insomnia is not always the first symptom of FFI; sometimes the first symptom is progressive dementia. When insomnia begins, it usually comes on suddenly and steadily worsens over a period of a few months. Other symptoms may include panic attacks, phobias, weight loss, lack of appetite, and having a body temperature which is too low or too high (hypothermia; hyperthermia). Autonomic disorders such as high blood pressure, episodes of hyperventilation, excessive sweating and salivation, and/or erectile dysfunction may occur.^[1]^[2]^[3]^[6]

As the disease progresses, most people with FFI develop abnormal, uncoordinated movements (ataxia), hallucinations, severe confusion (delerium), and muscle twitches and jerks (myoclonus). Although the dementia may begin as forgetfulness and confusion, it leads eventually to the inability to walk and talk. Total inability to sleep is common towards the end of the course of the disease.^[1]^[2]^[3]^[6]

Last updated: 11/30/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 18 |

Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormal autonomic nervous system physiology		0012332
Adult onset	Symptoms begin in adulthood	0003581
Apnea		0002104
Ataxia		0001251
Autosomal dominant inheritance		0000006
Childhood onset	Symptoms begin in childhood	0011463
Constipation		0002019
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Diplopia	Double vision	0000651
Dysarthria	Difficulty articulating speech	0001260
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Fever		0001945
Hyperhidrosis	Excessive sweating Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ]	0000975
Insomnia	Difficulty staying or falling asleep	0100785
Myoclonus		0001336
Neuronal loss in central nervous system	Loss of brain cells	0002529
Urinary retention		0000016
Weight loss		0001824

Showing of 18 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 3/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

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.^[2]^[3]^[4]^[9]

The abnormally shaped PrP (prion protein) causes changes in the thalamus including the progressive loss of neurons (nerve cells).^[2]^[3]^[6] 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.^[5]

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. ^[3]^[6]

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. ^[7] 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.^[11]

Last updated: 11/30/2016

Inheritance Inheritance

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.^[1] 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.^[1]^[12]

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.^[1]

In the rare sporadic cases of FFI, the disease is not inherited from either parent and cannot be passed down to their children.^[7]

Last updated: 11/30/2016

Diagnosis Diagnosis

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).^[1]^[2] The recommended PET scan is the fluorodeoxyglucose positron emission tomography (FDG-PET).^[9]

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.^[1]

Last updated: 11/30/2016

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

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.^[1]^[11] However research is ongoing and a number of potential treatments are being developed.^[2]^[4]^[7]^[8]

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.^[8] 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.^[4] 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.^[7]^[8]

Last updated: 12/2/2016

Prognosis Prognosis

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.^[2]^[9] 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.^[13]

Last updated: 11/30/2016

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Fatal familial insomnia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Creutzfeldt-Jakob Disease Foundation, Inc
3610 W. Market St.
Suite 110
Fiarlawn, OH 44333
Toll-free: 1-800-659-1991
Fax: +1-234-466-7077
E-mail: help@cjdfoundation.org
Website: https://cjdfoundation.org/

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Fatal familial insomnia. This website is maintained by the National Library of Medicine.
The Merck Manual provides information on this condition for patients and caregivers.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Fatal familial insomnia. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have had insomnia for months and believe I have fatal familial insomnia. The doctor says my sleep study shows I don't have it. How can he tell? See answer
Can you please tell me if there is a blood test that can determine if I have FFI? I have a very extreme insomnia. See answer

Have a question? Contact a GARD Information Specialist.

References References

Mastrianni JA. Genetic Prion Diseases. GeneReviews. January 2 2014; http://www.ncbi.nlm.nih.gov/books/NBK1229/.
Minikel EV. Introduction to fatal familial insomnia. Cure FFI Organization. December 3 2012; http://www.cureffi.org/2012/12/03/introduction-to-fatal-familial-insomnia/.
Llorens F, Thüne K, Schmitz M, Ansoleaga B, Frau-Méndez MA, Cramm M, Tahir W, Gotzmann N, Berjaoui S, Carmona M, Silva CJ, Fernandez-Vega I, José Zarranz J, Zerr I, and Ferrer I. Identification of new molecular alterations in fatal familial insomnia. Hum Mol Genet. April 7 2016; [Epub ahead of print]:http://www.ncbi.nlm.nih.gov/pubmed/27056979.
Forloni G, Tettamanti M, Lucca U, Albanese Y, Quaglio E, Chiesa R, Erbetta A, Villani F, Redaelli V, Tagliavini F, Artuso V, and Roiter I. Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases. Prion. March-April 2015; 9(2):75-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601344/.
Caswell J. When Stroke Affects the Thalamus. Stroke Connection Mag. Spring 2015; http://strokeconnection.strokeassociation.org/Spring-2015/When-Stroke-Affects-the-Thalamus/.
Frau-Méndez MA, Fernández-Vega I, Ansoleaga B, Blanco Tech R, Carmona Tech M, Antonio Del Rio J, Zerr I, Llorens F, José Zarranz J, and Ferrer I. Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus. Brain Pathol. June 24 2016; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/27338255.
Saa P, Harris DA and Cervenakova L. Mechanisms of prion-induced neurodegeneration. Expert Reveiws in Molecular Medicine. April 8 2016; 18(e5):1-18. https://www.ncbi.nlm.nih.gov/pubmed/27055367.
Burchell JT and Panegyres PK. Prion diseases: immunotargets and therapy. ImmunoTargets and Therapy. June 16 2016; 5:57-68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970640/.
Geschwind MD. Prion Diseases. Continuum Journal. December 2015; 21(6):1612-1638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879966/.
Peng B, Zhang S, Dong H, and Lu Z. Clinical, histopathological and genetic studies in a case of fatal familial insomnia with review of the literature. Int J Clin Exp Pathol. September 1 2015; 8(9):10171-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637540.
NINDS Transmissible Spongiform Encephalopathies Information Page. National Institute of Neurological Disorders and Stroke. February 2 2016; http://www.ninds.nih.gov/disorders/tse/tse.htm.
Minnekel E. Does this mean I'll definitely get the disease?. CureFFI. January 20, 2016; http://www.cureffi.org/2016/01/20/does-this-mean-ill-definitely-get-the-disease/.
Bichell RE. A Couple's Quest To Stop A Rare Disease Before It Takes One Of Them. National Public Radio (NPR). June 19, 2017; http://www.npr.org/sections/health-shots/2017/06/19/527795512/a-couples-quest-to-stop-a-rare-disease-before-it-takes-one-of-them.