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Perry syndrome

MedGen UID:
357007
Concept ID:
C1868594
Disease or Syndrome
Synonym: Parkinsonism with alveolar hypoventilation and mental depression
SNOMED CT: Perry syndrome (699184009); Parkinsonism with alveolar hypoventilation and mental depression (699184009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): DCTN1 (2p13.1)
 
Monarch Initiative: MONDO:0008201
OMIM®: 168605
Orphanet: ORPHA178509

Disease characteristics

Excerpted from the GeneReview: DCTN1-Related Neurodegeneration
The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide. [from GeneReviews]
Authors:
Jaroslaw Dulski  |  Takuya Konno  |  Zbigniew Wszolek   view full author information

Additional descriptions

From OMIM
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 autosomal dominant distal hereditary motor neuronopathy-14 (HMND14; 607641) and confer increased susceptibility to amyotrophic lateral sclerosis (ALS; see 105400).  http://www.omim.org/entry/168605
From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/perry-syndrome

Clinical features

From HPO
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Akinesia
MedGen UID:
43218
Concept ID:
C0085623
Finding
Inability to initiate changes in activity or movement and to perform ordinary volitional movements rapidly and easily.
Apathy
MedGen UID:
39083
Concept ID:
C0085632
Mental or Behavioral Dysfunction
Apathy is a quantitative reduction of motivation and the initiation and persistence of goal-directed behavior, where the accompanying emotions, thoughts, and social interactions are also suppressed.
Inappropriate behavior
MedGen UID:
66685
Concept ID:
C0233522
Mental or Behavioral Dysfunction
An explicit or perceived action, demonstration, conduct, or language (verbal and written) that is contrary to generally accepted norms, rules, procedures, or unacceptable within the context in which it is carried out. Inappropriate behaviors could take place in a sexual or social context and could be aggressive, violent, impulsive, intimidating, or threatening in nature.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Frontotemporal dementia
MedGen UID:
83266
Concept ID:
C0338451
Disease or Syndrome
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLALS7 (600795), caused by mutation in the CHMP2B gene (609512) on chromosome 3p11; inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS1 (105550), caused by mutation in the C9ORF72 gene (614260) on 9p21. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
Suicidal ideation
MedGen UID:
140856
Concept ID:
C0424000
Finding
Frequent thoughts about or preoccupation with killing oneself.
Disinhibition
MedGen UID:
633911
Concept ID:
C0474398
Finding
Reduced ability to control, or a failure to resist a temptation, urge, or impulse. Examples include disregard for social conventions, general impulsivity, and poor risk assessment.
Insomnia
MedGen UID:
214589
Concept ID:
C0917801
Sign or Symptom
Persistent difficulty initiating or maintaining sleep.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioral motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Hyperorality
MedGen UID:
325386
Concept ID:
C1838320
Finding
Hyperorality is a condition characterized by an excessive preoccupation with oral sensations and behaviors, such as chewing, sucking, biting, swallowing, and excessive mouthing of objects.
Short stepped shuffling gait
MedGen UID:
812045
Concept ID:
C3805715
Finding
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory arrest
MedGen UID:
57878
Concept ID:
C0162297
Pathologic Function
Cessation of breathing function.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Central hypoventilation
MedGen UID:
812169
Concept ID:
C3805839
Finding
Weak voice
MedGen UID:
66033
Concept ID:
C0241700
Finding
Reduced intensity (volume) of speech.
Mask-like facies
MedGen UID:
140860
Concept ID:
C0424448
Finding
A lack of facial expression often with staring eyes and a slightly open mouth.
Vertical supranuclear gaze palsy
MedGen UID:
334385
Concept ID:
C1843369
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Perry syndrome in Orphanet.

Professional guidelines

PubMed

Mishima T, Fujioka S, Tomiyama H, Yabe I, Kurisaki R, Fujii N, Neshige R, Ross OA, Farrer MJ, Dickson DW, Wszolek ZK, Hattori N, Tsuboi Y
J Neurol Neurosurg Psychiatry 2018 May;89(5):482-487. Epub 2017 Oct 31 doi: 10.1136/jnnp-2017-316864. PMID: 29089398Free PMC Article
Koh J, Ito H
Nihon Rinsho 2017 Jan;75(1):56-62. PMID: 30566295

Recent clinical studies

Etiology

Malaquias MJ, Igreja L, Nogueira C, Pereira C, Vilarinho L, Quelhas D, Freixo JP, Oliveira J, Magalhães M
Parkinsonism Relat Disord 2023 Jun;111:105408. Epub 2023 Apr 20 doi: 10.1016/j.parkreldis.2023.105408. PMID: 37105015
Pan X, Hong Q, Lu X, Li Z, Wang L, Chen W, Pan S
Behav Brain Res 2023 Mar 12;441:114284. Epub 2023 Jan 3 doi: 10.1016/j.bbr.2023.114284. PMID: 36608707
Richardson D, McEntagart MM, Isaacs JD
Pract Neurol 2020 Aug;20(4):317-319. Epub 2020 May 20 doi: 10.1136/practneurol-2020-002505. PMID: 32434902
Vilariño-Güell C, Wider C, Soto-Ortolaza AI, Cobb SA, Kachergus JM, Keeling BH, Dachsel JC, Hulihan MM, Dickson DW, Wszolek ZK, Uitti RJ, Graff-Radford NR, Boeve BF, Josephs KA, Miller B, Boylan KB, Gwinn K, Adler CH, Aasly JO, Hentati F, Destée A, Krygowska-Wajs A, Chartier-Harlin MC, Ross OA, Rademakers R, Farrer MJ
Neurology 2009 Jun 9;72(23):2024-8. doi: 10.1212/WNL.0b013e3181a92c4c. PMID: 19506225Free PMC Article

Diagnosis

Dulski J, Koga S, Prudencio M, Tipton PW, Ali S, Strongosky AJ, Rose JH, Parrales ZA, Dunmore JA, Jansen-West K, Petrucelli L, Dickson DW, Wszolek ZK
Parkinsonism Relat Disord 2023 Jul;112:105481. Epub 2023 Jun 13 doi: 10.1016/j.parkreldis.2023.105481. PMID: 37336025
Malaquias MJ, Igreja L, Nogueira C, Pereira C, Vilarinho L, Quelhas D, Freixo JP, Oliveira J, Magalhães M
Parkinsonism Relat Disord 2023 Jun;111:105408. Epub 2023 Apr 20 doi: 10.1016/j.parkreldis.2023.105408. PMID: 37105015
Dulski J, Cerquera-Cleves C, Milanowski L, Kwiatek-Majkusiak J, Koziorowski D, Ross OA, Pentela-Nowicka J, Sławek J, Wszolek ZK
Parkinsonism Relat Disord 2022 Jul;100:19-23. Epub 2022 Jun 4 doi: 10.1016/j.parkreldis.2022.05.023. PMID: 35691177
Dulski J, Cerquera-Cleves C, Milanowski L, Kidd A, Sitek EJ, Strongosky A, Vanegas Monroy AM, Dickson DW, Ross OA, Pentela-Nowicka J, Sławek J, Wszolek ZK
Eur J Neurol 2021 Dec;28(12):4010-4021. Epub 2021 Aug 26 doi: 10.1111/ene.15048. PMID: 34342072Free PMC Article
Konno T, Ross OA, Teive HAG, Sławek J, Dickson DW, Wszolek ZK
Parkinsonism Relat Disord 2017 Aug;41:14-24. Epub 2017 Jun 12 doi: 10.1016/j.parkreldis.2017.06.004. PMID: 28625595Free PMC Article

Therapy

Dulski J, Cerquera-Cleves C, Milanowski L, Kwiatek-Majkusiak J, Koziorowski D, Ross OA, Pentela-Nowicka J, Sławek J, Wszolek ZK
Parkinsonism Relat Disord 2022 Jul;100:19-23. Epub 2022 Jun 4 doi: 10.1016/j.parkreldis.2022.05.023. PMID: 35691177
Dulski J, Cerquera-Cleves C, Milanowski L, Kidd A, Sitek EJ, Strongosky A, Vanegas Monroy AM, Dickson DW, Ross OA, Pentela-Nowicka J, Sławek J, Wszolek ZK
Eur J Neurol 2021 Dec;28(12):4010-4021. Epub 2021 Aug 26 doi: 10.1111/ene.15048. PMID: 34342072Free PMC Article
Felicio AC, Dinelle K, Agarwal PA, McKenzie J, Heffernan N, Road JD, Appel-Cresswell S, Wszolek ZK, Farrer MJ, Schulzer M, Sossi V, Stoessl AJ
Mov Disord 2014 Aug;29(9):1197-201. Epub 2014 May 5 doi: 10.1002/mds.25893. PMID: 24797316Free PMC Article
Newsway V, Fish M, Rohrer JD, Majounie E, Williams N, Hack M, Warren JD, Morris HR
Mov Disord 2010 Apr 30;25(6):767-70. doi: 10.1002/mds.22950. PMID: 20437543Free PMC Article

Prognosis

Dulski J, Koga S, Prudencio M, Tipton PW, Ali S, Strongosky AJ, Rose JH, Parrales ZA, Dunmore JA, Jansen-West K, Petrucelli L, Dickson DW, Wszolek ZK
Parkinsonism Relat Disord 2023 Jul;112:105481. Epub 2023 Jun 13 doi: 10.1016/j.parkreldis.2023.105481. PMID: 37336025
Pan X, Hong Q, Lu X, Li Z, Wang L, Chen W, Pan S
Behav Brain Res 2023 Mar 12;441:114284. Epub 2023 Jan 3 doi: 10.1016/j.bbr.2023.114284. PMID: 36608707
Zhang J, Wang H, Liu W, Wang J, Zhang J, Chang X, Huang S, Pang X, Guo J, Wang Q, Zhang W
Neurol Sci 2021 Sep;42(9):3695-3705. Epub 2021 Jan 14 doi: 10.1007/s10072-020-04962-w. PMID: 33443672
Čierny M, Hooshmand SI, Fee D, Tripathi S, Dsouza NR, La Pean Kirschner A, Zimmermann MT, Brennan R
Parkinsonism Relat Disord 2020 Aug;77:110-113. Epub 2020 Jun 25 doi: 10.1016/j.parkreldis.2020.06.006. PMID: 32712562
Richardson D, McEntagart MM, Isaacs JD
Pract Neurol 2020 Aug;20(4):317-319. Epub 2020 May 20 doi: 10.1136/practneurol-2020-002505. PMID: 32434902

Clinical prediction guides

Dulski J, Koga S, Prudencio M, Tipton PW, Ali S, Strongosky AJ, Rose JH, Parrales ZA, Dunmore JA, Jansen-West K, Petrucelli L, Dickson DW, Wszolek ZK
Parkinsonism Relat Disord 2023 Jul;112:105481. Epub 2023 Jun 13 doi: 10.1016/j.parkreldis.2023.105481. PMID: 37336025
Dulski J, Cerquera-Cleves C, Milanowski L, Kwiatek-Majkusiak J, Koziorowski D, Ross OA, Pentela-Nowicka J, Sławek J, Wszolek ZK
Parkinsonism Relat Disord 2022 Jul;100:19-23. Epub 2022 Jun 4 doi: 10.1016/j.parkreldis.2022.05.023. PMID: 35691177
Mishima T, Fujioka S, Fukae J, Yuasa-Kawada J, Tsuboi Y
Int J Mol Sci 2018 Dec 4;19(12) doi: 10.3390/ijms19123870. PMID: 30518093Free PMC Article
Mishima T, Koga S, Lin WL, Kasanuki K, Castanedes-Casey M, Wszolek ZK, Oh SJ, Tsuboi Y, Dickson DW
J Neuropathol Exp Neurol 2017 Aug 1;76(8):676-682. doi: 10.1093/jnen/nlx049. PMID: 28789478Free PMC Article
Chung EJ, Hwang JH, Lee MJ, Hong JH, Ji KH, Yoo WK, Kim SJ, Song HK, Lee CS, Lee MS, Kim YJ
Parkinsonism Relat Disord 2014 Apr;20(4):388-93. Epub 2014 Jan 22 doi: 10.1016/j.parkreldis.2014.01.010. PMID: 24484619

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