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Disease Profile

Perry syndrome

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

US Estimated

Europe Estimated

Age of onset






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


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.


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.


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


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.


Not applicable


Other names (AKA)

Parkinsonism with alveolar hypoventilation and mental depression


Congenital and Genetic Diseases; Nervous System Diseases


The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 178509

A rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression.

The prevalence is unknown. It has been described in 53 cases from 11 families to date in Canada, U.S., U.K., France, Turkey and Japan.

Clinical description
Perry syndrome has a mean age of onset of 48 years (range 35-61) and presents with parkinsonism (akinetic-rigid and rather symmetric), psychiatric changes manifesting as depression, lethargy, withdrawal, apathy, and changes in character, as well as sleep difficulties. The usual duration of Perry syndrome is about 5 years, with severe weight loss and central hypoventilation being seen late in the disease course. Marked autonomic dysfunction was reported in one family from Japan. Patients are often bedridden or wheelchair bound as motor impairment may be severe at a later stage of the disease.

Perry syndrome is caused by mutations (five identified to date) in exon 2 of the dynactin DCTN1 gene coding for p150glued, the major subunit of the dynactin protein complex. Mutations in this gene alter the binding affinity of dynactin for microtubules and consequently this leads to the impairment of this important transport protein. Nigral neurons seem to be more affected by the dysfunction of this protein, explaining their increased cell death and the distinct pathology seen in Perry syndrome.

Diagnostic methods
Diagnosis is based on clinical findings of early-onset parkinsonism combined with depression, weight loss and hypoventilation and is confirmed by a molecular genetic test finding a mutation in the DCTN1 gene. Major histological findings consist of neuronal loss and TAR DNA-binding protein (TDP-43)-positive pathology in the substantia nigra and locus coeruleus, without Lewy bodies. Sleep studies should be performed to detect hypoventilation.

Differential diagnosis
The main differential diagnoses are other forms of familial early-onset parkinsonism (in particular those associated with mutations in the PARK2, PINK1, PARK7 and LRRK2 genes) as well as frontotemporal dementia (see these terms).

Antenatal diagnosis
Antenatal diagnosis is possible in laboratories that offer custom prenatal testing for families with a known DCTN1 mutation.

Genetic counseling
Perry syndrome is inherited in an autosomal dominant manner with full penetrance and children of a parent with the disease have a 50% chance of also having the mutation and developing the disease. Pre-symptomatic diagnosis can be offered to at-risk individuals.

Management and treatment
There is no cure for Perry syndrome. Symptomatic treatment requires a multidisciplinary team. Dopaminergic therapy is given to patients to help with parkinsonism, usually using levodopa / carbidopa. Response to levodopa can be erratic or absent but large doses (>2g) have been successful in reducing symptoms in several patients. Patients with hypoventilation require ventilator support (invasive or non-invasive), particularly at night. Respiratory function should be monitored continuously. Psychiatric follow-up along with antidepressant drugs are needed to manage depression and prevent suicide. Weight should be monitored and a high caloric diet should be implemented when weight loss is present. With worsening symptoms hospitalization and major medical assistance is often required.

Perry syndrome progresses rapidly and the prognosis is poor. Death is due to respiratory insufficiency or suicide or, in some cases, can be sudden and unexplained. Ventilation assistance may prolong survival with an acceptable quality of life.

Visit the Orphanet disease page for more resources.


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:
80%-99% of people have these symptoms
Lack of feeling, emotion, interest
Central hypoventilation
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

Weight loss
5%-29% of people have these symptoms
Dementia, progressive
Progressive dementia

[ more ]

Low blood pressure
Personality changes
Personality change
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

Autosomal dominant inheritance
Slow movements
Slowness of movements

[ more ]

Difficulty articulating speech
Frontotemporal dementia
Slow breathing
Under breathing

[ more ]

Inappropriate behavior
Difficulty staying or falling asleep
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance

[ more ]

Rapidly progressive
Worsening quickly
Respiratory insufficiency
Respiratory impairment
Muscle rigidity
Short stepped shuffling gait
Short stepped shuffling walk
Vertical supranuclear gaze palsy
Weak voice
Soft voice


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.

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 Genetics contains information on Perry syndrome. This website is maintained by the National Library of Medicine.

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.
  • 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 Perry syndrome. Click on the link to view a sample search on this topic.