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Progressive supranuclear palsy

Reviewed March 2011

What is progressive supranuclear palsy?

Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.

Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.

Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after signs and symptoms first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.

Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living.

How common is progressive supranuclear palsy?

The exact prevalence of progressive supranuclear palsy is unknown. It may affect about 6 in 100,000 people worldwide.

What genes are related to progressive supranuclear palsy?

In most cases, the genetic cause of progressive supranuclear palsy is unknown. Rarely, the disease results from mutations in the MAPT gene. Certain normal variations (polymorphisms) in the MAPT gene have also been associated with an increased risk of developing progressive supranuclear palsy.

The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, including in nerve cells (neurons) in the brain. It is involved in assembling and stabilizing microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.

The signs and symptoms of progressive supranuclear palsy appear to be related to abnormalities in the tau protein. In people with MAPT gene mutations, genetic changes disrupt the protein's normal structure and function. However, abnormal tau is also found in affected individuals without MAPT gene mutations. The defective tau protein assembles into abnormal clumps within neurons and other brain cells, although it is unclear what effect these clumps have on cell function and survival. Progressive supranuclear palsy is characterized by the gradual death of brain cells, particularly in structures deep within the brain that are essential for coordinating movement. This loss of brain cells underlies the movement abnormalities and other features of progressive supranuclear palsy.

This condition is one of several related diseases known as tauopathies, which are characterized by an abnormal buildup of tau in the brain.

Researchers suspect that other genetic and environmental factors also contribute to progressive supranuclear palsy. For example, the disease has been linked to genetic changes on chromosome 1 and chromosome 11. However, the specific genes involved have not been identified.

Related Gene(s)

Changes in this gene are associated with progressive supranuclear palsy.

  • MAPT

How do people inherit progressive supranuclear palsy?

Most cases of progressive supranuclear palsy are sporadic, which means they occur in people with no history of the disorder in their family. However, some people with this disorder have had family members with related conditions, such as parkinsonism and a loss of intellectual functions (dementia).

When progressive supranuclear palsy runs in families, it can have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of progressive supranuclear palsy?

These resources address the diagnosis or management of progressive supranuclear palsy and may include treatment providers.

  • Gene Review: MAPT-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1505/)
  • Genetic Testing Registry: Progressive supranuclear ophthalmoplegia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0038868)
  • Genetic Testing Registry: Supranuclear palsy, progressive, 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1836148)
  • Genetic Testing Registry: Supranuclear palsy, progressive, 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970476)

You might also find information on the diagnosis or management of progressive supranuclear palsy in Educational resources (http://www.ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about progressive supranuclear palsy?

You may find the following resources about progressive supranuclear palsy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for progressive supranuclear palsy?

  • progressive supranuclear ophthalmoplegia
  • PSP
  • Richardson's syndrome
  • Steele-Richardson-Olszewski syndrome
  • supranuclear palsy, progressive

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about progressive supranuclear palsy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding progressive supranuclear palsy?

autosomal ; autosomal dominant ; bradykinesia ; cell ; cell division ; chromosome ; cognition ; cytoskeleton ; dementia ; dysarthria ; dysphagia ; gait ; gene ; haplotype ; inheritance ; nervous system ; neurofibrillary tangles ; ophthalmoplegia ; palsy ; parkinsonism ; pattern of inheritance ; photophobia ; prevalence ; protein ; sensitivity ; sporadic ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Conrad C, Andreadis A, Trojanowski JQ, Dickson DW, Kang D, Chen X, Wiederholt W, Hansen L, Masliah E, Thal LJ, Katzman R, Xia Y, Saitoh T. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol. 1997 Feb;41(2):277-81. (http://www.ncbi.nlm.nih.gov/pubmed/9029080?dopt=Abstract)
  • Donker Kaat L, Boon AJ, Azmani A, Kamphorst W, Breteler MM, Anar B, Heutink P, van Swieten JC. Familial aggregation of parkinsonism in progressive supranuclear palsy. Neurology. 2009 Jul 14;73(2):98-105. doi: 10.1212/WNL.0b013e3181a92bcc. Epub 2009 May 20. (http://www.ncbi.nlm.nih.gov/pubmed/19458322?dopt=Abstract)
  • Gene Review: MAPT-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1505/)
  • Houghton DJ, Litvan I. Unraveling progressive supranuclear palsy: from the bedside back to the bench. Parkinsonism Relat Disord. 2007;13 Suppl 3:S341-6. doi: 10.1016/S1353-8020(08)70028-2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18267262?dopt=Abstract)
  • Litvan I, Mangone CA, McKee A, Verny M, Parsa A, Jellinger K, D'Olhaberriague L, Chaudhuri KR, Pearce RK. Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):615-20. (http://www.ncbi.nlm.nih.gov/pubmed/8648326?dopt=Abstract)
  • Litvan I. Diagnosis and management of progressive supranuclear palsy. Semin Neurol. 2001;21(1):41-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11346024?dopt=Abstract)
  • Melquist S, Craig DW, Huentelman MJ, Crook R, Pearson JV, Baker M, Zismann VL, Gass J, Adamson J, Szelinger S, Corneveaux J, Cannon A, Coon KD, Lincoln S, Adler C, Tuite P, Calne DB, Bigio EH, Uitti RJ, Wszolek ZK, Golbe LI, Caselli RJ, Graff-Radford N, Litvan I, Farrer MJ, Dickson DW, Hutton M, Stephan DA. Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms. Am J Hum Genet. 2007 Apr;80(4):769-78. Epub 2007 Mar 8. (http://www.ncbi.nlm.nih.gov/pubmed/17357082?dopt=Abstract)
  • Rademakers R, Melquist S, Cruts M, Theuns J, Del-Favero J, Poorkaj P, Baker M, Sleegers K, Crook R, De Pooter T, Bel Kacem S, Adamson J, Van den Bossche D, Van den Broeck M, Gass J, Corsmit E, De Rijk P, Thomas N, Engelborghs S, Heckman M, Litvan I, Crook J, De Deyn PP, Dickson D, Schellenberg GD, Van Broeckhoven C, Hutton ML. High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy. Hum Mol Genet. 2005 Nov 1;14(21):3281-92. Epub 2005 Sep 29. (http://www.ncbi.nlm.nih.gov/pubmed/16195395?dopt=Abstract)
  • Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009 Mar;8(3):270-9. doi: 10.1016/S1474-4422(09)70042-0. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19233037?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2011
Published: April 17, 2014