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Disease Profile

Fatal familial insomnia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adult

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ICD-10

A81.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Familial fatal insomnia; Insomnia familial fatal

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Fatal familial insomnia (FFI) affects the thalamus, the part of the brain that controls the sleep-wake cycle. Symptoms typically begin between the ages of 40-60 years. The most common symptoms are sleep disturbance, psychiatric problems, weight loss, and balance problems. Other symptoms include high blood pressure, excess sweating, and difficulty controlling body temperature. These symptoms tend to get worse over time. FFI is usually fatal in 6-36 months. Almost all cases of FFI occur due to a specific variant in the PRNP gene and are inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, sleep study, and imaging studies. The results of genetic testing can help confirm the diagnosis. Treatment for FFI is focused on managing the symptoms.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms in people with fatal familial insomnia (FFI). These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Symptoms of FFI may include:[1][2][4]

  • Inability to fall asleep or stay asleep (insomnia)
  • Difficulty thinking and concentrating (cognitive impairment)
  • Short-term memory loss
  • Weight loss
  • Difficulty coordinating movements
  • High blood pressure
  • Inability to maintain body temperature
  • Excessive sweating and tearing

The first symptoms of FFI usually begin between the ages of 40 and 60 years. Initial symptoms usually include difficulty sleeping and problems with thinking and concentration. The insomnia gets worse over time, leading to high blood pressure, rapid heart rate, weight loss, and trouble controlling body temperature. Other symptoms that may develop include uncoordinated movements (ataxia), hallucinations, severe confusion (delirium), and difficulty swallowing. Death usually occurs within 6-36 months after symptoms begin. Death is usually due to heart problems or infections.[1][2][4]

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.

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

Cause

Fatal familial insomnia (FFI) occurs when the PRNP gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all. In almost every case, FFI is caused by a very specific variant in the PRNP gene.[1][2]

Diagnosis

Fatal familial insomnia (FFI) is diagnosed based on the symptoms, clinical exam, a sleep study (polysomnography), and imaging tests. The results of genetic testing may be helpful to help confirm the diagnosis.[1][2] A list of features for diagnosing FFI (diagnostic criteria) has been published.[15895][15897]

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 for fatal familial insomnia (FFI) is focused on managing the symptoms and providing comfort for the person with FFI.[1][2]

    Specialists involved in the care of someone with FFI may include:

    • Neurologist
    • Medical geneticist
    • Social worker

    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

      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

        In-Depth Information

        • 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.

          References

          1. Khan Z, Bollu PC.. Fatal Familial Insomnia.. StatPearls. Updated May 27, 2020; https://pubmed.ncbi.nlm.nih.gov/29489284/.
          2. Cracco L, Appleby BS, Gambetti P. Fatal familial insomnia and sporadic fatal insomnia. Handb Clin Neurol. 2018;153:271-299. 2018; 153:271-299. https://pubmed.ncbi.nlm.nih.gov/29887141/.
          3. Baldelli L, Provini F. Fatal familial insomnia and Agrypnia Excitata: Autonomic dysfunctions and pathophysiological implications. Auton Neurosci. May 2019; 218:68-86. https://pubmed.ncbi.nlm.nih.gov/30890351/.
          4. Wu LY, Zhan SQ, Huang ZY, Zhang B, Wang T, Liu CF, et al. Expert Consensus on Clinical Diagnostic Criteria for Fatal Familial Insomnia.. Chin Med J (Engl). Jul 5, 2018; 131(13):1613-1617. https://pubmed.ncbi.nlm.nih.gov/29941716/.
          5. Baldwin KJ, Correll CM. Prion Disease. Semin Neurol. Aug 2019; 39(4):428-439. https://pubmed.ncbi.nlm.nih.gov/31533183/.
          6. 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/.
          7. Krasnianski A, Bartl M, Sanchez Juan PJ, et al. Fatal familial insomnia: clinical features and early identification. Ann Neurol. 2008; 63(05):658-661. https://pubmed.ncbi.nlm.nih.gov/18360821/.

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