Perry Syndrome (PERRYS)

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Disease Ontology 12 DOID:0060486 OMIM 56 168605 KEGG 36 H00879 MeSH 43 C566822 D003863 D007040 D020734 more UMLS via Orphanet 72 C1868594

Orphanet 58 ORPHA178509 MedGen 41 C1868594 SNOMED-CT via HPO 68 102943000 103606006 112082005 15993004 16046003 161832001 192073007 193462001 20602000 21061000119107 230270009 246773002 26079004 262285001 263681008 31515003 32798002 34527004 35489007 399317006 409623005 45007003 52448006 53888004 78667006 8011004 80954004 8614008 89362005 more UMLS 71 C1868594

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 178509 Definition A rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression. Epidemiology 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. Etiology 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. Prognosis 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.

MalaCards based summary : Perry Syndrome, also known as parkinsonism with alveolar hypoventilation and mental depression, is related to pure autonomic failure and neuronopathy, distal hereditary motor, type viib, and has symptoms including sleeplessness An important gene associated with Perry Syndrome is DCTN1 (Dynactin Subunit 1), and among its related pathways/superpathways are Cytoskeletal Signaling and Neuroscience. Affiliated tissues include brain and testes, and related phenotypes are sleep disturbance and weight loss

Disease Ontology : ¹² A syndrome characterized by parkinsonism, hypoventilation, depression, and weight loss and that has material basis in heterozygous mutation in the DCTN1 gene on chromosome 2p13.

Genetics Home Reference : ²⁵ Perry syndrome is a progressive brain disease that is characterized by four major features: a pattern of movement abnormalities known as parkinsonism, psychiatric changes, weight loss, and abnormally slow breathing (hypoventilation). These signs and symptoms typically appear in a person's forties or fifties. Parkinsonism and psychiatric changes are usually the earliest features of Perry syndrome. Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. These movement abnormalities are often accompanied by changes in personality and behavior. The most frequent psychiatric changes that occur in people with Perry syndrome include depression, a general loss of interest and enthusiasm (apathy), withdrawal from friends and family, and suicidal thoughts. Many affected individuals also experience significant, unexplained weight loss early in the disease. Hypoventilation is a later feature of Perry syndrome. Abnormally slow breathing most often occurs at night, causing affected individuals to wake up frequently. As the disease worsens, hypoventilation can result in a life-threatening lack of oxygen and respiratory failure. People with Perry syndrome typically survive for about 5 years after signs and symptoms first appear. Most affected individuals ultimately die of respiratory failure or pneumonia. Suicide is another cause of death in this condition.

OMIM : ⁵⁶ Perry syndrome is an autosomal dominant neurodegenerative disorder classically characterized by adult-onset parkinsonism and depression, followed by weight loss and respiratory hypoventilation (Perry et al., 1975). The phenotype has subsequently been expanded to include features that overlap with other neurodegenerative conditions, including frontotemporal dementia (see, e.g., 600274) and progressive supranuclear palsy (PSP; 601104). There is intrafamilial variation in the manifestations of the disorder (summary by Caroppo et al., 2014; review by Wider et al., 2010). Mutation in the DCTN1 gene can also cause distal motor neuronopathy type VIIB (HMN7B; 607641) and confer increased susceptibility to amyotrophic lateral sclerosis (ALS; see 105400). (168605)

KEGG : ³⁶ Perry syndrome is a rapidly progressive, autosomal dominant, neurodegenerative disorder. The cardinal symptoms consist of parkinsonism, depression, severe weight loss and hypoventilation. At a molecular level, Perry syndrome is characterized by TDP-43 inclusions indicating a pathological overlap with amyotrophic lateral sclerosis (ALS) and some forms of frontotemporal lobar degeneration (FTLD). Perry syndrome has recently been identified as being due to mutations in the DCTN1 gene, encoding the component of the dynactin complex.

UniProtKB/Swiss-Prot : ⁷³ Perry syndrome: A neuropsychiatric disorder characterized by mental depression not responsive to antidepressant drugs or electroconvulsive therapy, sleep disturbances, exhaustion and marked weight loss. Parkinsonism develops later and respiratory failure occurred terminally.

GeneReviews: NBK47027

Clinical features from OMIM:

168605

Search Clinical Trials , NIH Clinical Center for Perry Syndrome

Search GEO for disease gene expression data for Perry Syndrome.