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Disease Profile

Progressive supranuclear palsy

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adult

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ICD-10

G23.1

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.

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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)

Supranuclear palsy, progressive; PSP; Steele-Richardson-Olszewski Syndrome;

Summary

Progressive supranuclear palsy (PSP) is a degenerative neurologic disease due to damage to nerve cells in the brain.[1] Signs and symptoms vary but may include loss of balance; blurring of vision; problems controlling eye movement; changes in mood, behavior and judgment; cognitive decline; and slowing and slurred speech. PSP is often misdiagnosed as Parkinson disease due to similar symptoms. Onset is usually after age 60 but may occur earlier. Most cases of PSP appear to be sporadic, but familial cases have been reported. Some cases have been found to be caused by a mutation in the MAPT gene, and other genetic factors are being studied. There is currently no effective treatment for PSP, and symptoms usually do not respond to medications. Research regarding potential treatments is ongoing.[1][2]

Symptoms

Progressive supranuclear palsy (PSP) causes a wide range of symptoms that differ among affected people. Most commonly, the first symptom is losing balance while walking, which may cause unexplained falls. Other common early symptoms include changes in personality, mood and behavior; irritability; and forgetfulness.[1]

As PSP progresses, most people develop blurring of vision and problems controlling eye movement. This can lead to involuntarily closing the eyes; prolonged or infrequent blinking; or difficulty opening the eyes. Some people have trouble maintaining eye contact during a conversation.[1]

Other issues develop as the disease advances, including slow movement (bradykinesia), clumsiness, and stiffness. These problems worsen with time, with most affected people ultimately needing a wheelchair.[3] Weakening of the muscles in the mouth, tongue and throat lead to slurred speech and difficulty swallowing. This often causes aspiration pneumonia, the most common cause of death in people with PSP.[1]

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
80%-99% of people have these symptoms
Abnormal synaptic transmission
0012535
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Falls
0002527
Impulsivity
Impulsive
0100710
Neuronal loss in central nervous system
Loss of brain cells
0002529
Postural instability
Balance impairment
0002172
Supranuclear ophthalmoplegia
0000623
Unsteady gait
Unsteady walk
0002317
30%-79% of people have these symptoms
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Blepharospasm
Eyelid spasm
Eyelid twitching
Involuntary closure of eyelid
Spontaneous closure of eyelid

[ more ]

0000643
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Depressivity
Depression
0000716
Gliosis
0002171
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Pseudobulbar signs
0002200
Slow saccadic eye movements
Slow eye movements
0000514
Vertical supranuclear gaze palsy
0000511
5%-29% of people have these symptoms
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Rigidity
Muscle rigidity
0002063
Tremor
0001337
1%-4% of people have these symptoms
Frontal release signs
0000743
Limb dystonia
0002451
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Akinesia
0002304
Apathy
Lack of feeling, emotion, interest
0000741
Autosomal dominant inheritance
0000006
Axial dystonia
0002530
Blurred vision
0000622
Diplopia
Double vision
0000651
Dysarthria
Difficulty articulating speech
0001260
Eyelid apraxia
Difficulty opening the eyelids
0000658
Frontolimbic dementia
0002439
Gait imbalance
Abnormality of balance
Abnormality of equilibrium
Imbalanced walk

[ more ]

0002141
Granulovacuolar degeneration
0002528
Irritability
Irritable
0000737
Mutism
Inability to speak
Muteness

[ more ]

0002300
Neurofibrillary tangles
0002185
Neuronal loss in basal ganglia
0200147
Parkinsonism
0001300
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Retrocollis
0002544
Supranuclear gaze palsy
0000605

Cause

While progressive supranuclear palsy (PSP) is usually sporadic, some cases run in families. In most cases, the genetic cause is unknown, but some are due to mutations or "variations" in the MAPT gene.

The MAPT gene gives the body instructions to make a protein called tau. This protein is found in nerve cells (neurons) in the brain and in other parts of the nervous system. It plays a part in putting together and stabilizing components of the structure of cells, helping cells to keep their shape, and aiding in cell division and the transport of materials. It appears that gene mutations or variations that affect the function of the tau protein cause PSP, or cause an increased risk for a person to develop PSP.

Abnormal tau is also found in people with PSP who don't have MAPT mutations. Therefore, researchers think that additional genetic and environmental factors contribute to the development of PSP. However, other specific genes that may be involved have not yet been identified.[3]

Diagnosis

Progressive supranuclear palsy (PSP) is usually sporadic (not inherited), but in rare cases it can be inherited. While the genetic cause of PSP not usually known, it can be caused by a mutation in a gene called MAPT. To our knowledge, MAPT is currently the only gene for which clinical genetic testing for PSP is available. This means that if a person with PSP is found to have a disease-causing mutation in the MAPT gene, genetic testing of other family members for the same mutation in this gene may be available. Each child of a person with PSP caused by a MAPT mutation has a 50% chance to inherit the mutated gene. However, if a person with PSP does not have a mutation in the MAPT gene (which is most often the case), clinical genetic testing for other family members is not available.

The Genetic Testing Registry (GTR) provides information about the genetic tests available for PSP. People interested in genetic testing for PSP are encouraged to speak with a genetics professional for additional information.

Progressive supranuclear palsy (PSP) is often hard to diagnose because its symptoms can be similar to those of other, more common movement disorders. It may also be hard to diagnose because some of the most characteristic symptoms may develop late, or not at all.[5]

A diagnosis of PSP is currently based on the signs and symptoms present (clinical features).[5] Identifying early gait instability and difficulty moving the eyes (the hallmark of the disease), as well as ruling out other conditions, are most important.[1] There is no laboratory test or imaging study that is diagnostic. Identifying neurofibrillary tangles (aggregates of tau) in their characteristic distribution aids in the diagnosis.[5]

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

    There are currently no treatments that alter the course of disease for people with progressive supranuclear palsy (PSP), and no drugs that provide significant relief of symptoms.[5] However, supportive treatment may be helpful and may include:

    • Management of dysphagia and dysarthria with the help of dietitians as well as speech and language therapists
    • Early occupational therapy to promote longer independence in performing activities of daily living
    • The use of mirror-prism lenses for those with severe limitation of extraocular movements to read and feed themselves
    • The use of eyelid crutches, alone or in combination with botox therapy, for inability to open the eyes and blepharospasm
    • Physical therapy for symptomatic treatment of postural instability and falls, including gait and balance training[5]

    A surgical procedure called a gastrostomy may be necessary when there are swallowing disturbances or a high risk of severe choking.[1]

    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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Progressive supranuclear palsy. This website is maintained by the National Library of Medicine.
      • 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.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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 Progressive supranuclear palsy. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Progressive Supranuclear Palsy Fact Sheet. NINDS. November 5, 2015; https://www.ninds.nih.gov/disorders/psp/detail_psp.htm.
            2. Im SY, Kim YE, Kim YJ. Genetics of Progressive Supranuclear Palsy. J Mov Disord. September, 2015; 8(3):122-129.
            3. Progressive Supranuclear Palsy. Genetics Home Reference. May, 2015; https://ghr.nlm.nih.gov/condition/progressive-supranuclear-palsy.
            4. Progressive supranuclear palsy. NORD. 2014; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/287/viewAbstract.
            5. Stewart A Factor, Christine Doss Esper. Progressive supranuclear palsy (PSP). UpToDate. Waltham, MA: UpToDate; December, 2015;

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