Perry syndrome is a rare, progressive, hereditary neurodegenerative movement disorder and TDP-43 proteinopathy.
Perry syndrome is considered to be very rare, generally isolated to select families who carry the mutation implicated in the disease 1,2. In one study, the age on onset was found to be approximately 50 years, with a range of 35-70 years 2.
Perry syndrome is classically characterized by 1-3:
- parkinsonism: rigidity, tremor, bradykinesia, and postural instability
- psychiatric symptoms: apathy and depression
- respiratory compromise: central hypoventilation and central sleep apnea
- weight loss: unintentional and progressive in nature
In addition to these features, patients many have a wide array of other neurological symptoms, such as presence of frontal signs, oculomotor disorders, dysphagia, dementia, and autonomic dysfunction 1.
Perry syndrome is an autosomal dominant disorder, caused by mutation to the DCTN1 gene, on chromosome 2p13.1. The DCTN1 gene encodes for dynactin-1, which plays a vital role in transport of materials within neurons 1-3. In Perry syndrome, this process is impaired, resulting in progressive neuronal loss. In particular, neuronal loss is most marked in the substantia nigra 1-3. However there is also involvement in other parts of the central nervous system, such as other regions of the basal ganglia and brainstem, with notable sparing of the cortex 1-3. Progressive neuronal loss in these regions results in the described clinical phenotype.
Affected regions of the brain in Perry syndrome unsurprisingly demonstrate neuronal loss and gliosis 1-3. Furthermore, on immunostaining, neurons may have abnormal transactive response DNA-binding protein of 43 kDa (TDP-43)-positive cytoplasmic inclusions 1-4. Thus, Perry syndrome is considered a TDP-43 proteinopathy.
Neuroimaging in Perry syndrome is often unremarkable, however there may be some subtle changes in patients with certain clinical features 1,2. For example, MRI brain may reveal frontotemporal atrophy, which may be more likely to be present in patients with Perry syndrome with concurrent frontal signs 5. Similarly, in patients with concurrent oculomotor signs, there may be midbrain atrophy noted 6.
Treatment and prognosis
Management of Perry syndrome is symptomatic, such as trialing levodopa therapy for parkinsonism, and managing respiratory symptoms with non-invasive ventilation or diaphragmatic pacemaker insertion 2,7.
Unfortunately, Perry syndrome is a progressive condition that is ultimately fatal, often due to respiratory complications, with one study finding a median disease duration of 5 years 2.
History and etymology
The syndrome was first described in a Canadian family by Thomas L Perry and colleagues in their 1975 seminal case series 8.
- 1. 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. Establishing diagnostic criteria for Perry syndrome. (2018) Journal of neurology, neurosurgery, and psychiatry. 89 (5): 482-487. doi:10.1136/jnnp-2017-316864 - Pubmed
- 2. Konno T, Ross OA, Teive HAG, Sławek J, Dickson DW, Wszolek ZK. DCTN1-related neurodegeneration: Perry syndrome and beyond. (2017) Parkinsonism & related disorders. 41: 14-24. doi:10.1016/j.parkreldis.2017.06.004 - Pubmed
- 3. Farrer MJ, Hulihan MM, Kachergus JM, Dächsel JC, Stoessl AJ, Grantier LL, Calne S, Calne DB, Lechevalier B, Chapon F, Tsuboi Y, Yamada T, Gutmann L, Elibol B, Bhatia KP, Wider C, Vilariño-Güell C, Ross OA, Brown LA, Castanedes-Casey M, Dickson DW, Wszolek ZK. DCTN1 mutations in Perry syndrome. (2009) Nature genetics. 41 (2): 163-5. doi:10.1038/ng.293 - Pubmed
- 4. Wider C, Dickson DW, Stoessl AJ, Tsuboi Y, Chapon F, Gutmann L, Lechevalier B, Calne DB, Personett DA, Hulihan M, Kachergus J, Rademakers R, Baker MC, Grantier LL, Sujith OK, Brown L, Calne S, Farrer MJ, Wszolek ZK. Pallidonigral TDP-43 pathology in Perry syndrome. (2009) Parkinsonism & related disorders. 15 (4): 281-6. doi:10.1016/j.parkreldis.2008.07.005 - Pubmed
- 5. Araki E, Tsuboi Y, Daechsel J, Milnerwood A, Vilarino‐Guell C, Fujii N, Mishima T, Oka T, Hara H, Fukae J, Farrer MJ. A Novel DCTN1 mutation with late‐onset parkinsonism and frontotemporal atrophy. (2014) Movement Disorders. 29 (9): 1201. doi:10.1002/mds.25833 - Pubmed
- 6. Newsway V, Fish M, Rohrer JD, Majounie E, Williams N, Hack M, Warren JD, Morris HR. Perry syndrome due to the DCTN1 G71R mutation: a distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure. (2010) Movement disorders : official journal of the Movement Disorder Society. 25 (6): 767-70. doi:10.1002/mds.22950 - Pubmed
- 7. Pretelt F, Castañeda Cardona C, Tacik P, Ross OA, Wszolek ZK. Latin America's first case of Perry syndrome and a new treatment option for respiratory insufficiency. (2014) Journal of neurology. 261 (3): 620-1. doi:10.1007/s00415-014-7262-6 - Pubmed
- 8. Perry TL, Bratty PJA, Hansen S, Kennedy J, Urquhart N, Dolman CL. Hereditary Mental Depression and Parkinsonism With Taurine Deficiency. (1975) Archives of Neurology. 32 (2): 108. doi:10.1001/archneur.1975.00490440058009
Related Radiopaedia articles
Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.
neurodegenerative MRI brain (an approach)
- measurements and ratios
- midbrain to pons area ratio (for PSP)
- Magnetic Resonance Parkinsonism Index (MRPI) (for PSP)
- frontal horn width to intercaudate distance ratio (FH/CC) (for Huntington disease)
- intercaudate distance to inner table width ratio (CC/IT) (for Huntington disease)
- scoring systems
- measurements and ratios
- typical/classical Alzheimer disease
- variant (e.g. posterior cortical atrophy)
- chronic traumatic encephalopathy (CTE)
- corticobasal degeneration
- frontotemporal lobar degeneration (FTLD) (not all are tau)
- Pick disease
- progressive supranuclear palsy (PSP)
- Alzheimer disease
- cerebral amyloid angiopathy (CAA)
- transthyretine-associated cerebral amyloidosis
- neuronal intranuclear hyaline inclusion disease (NIHID)
- TDP-43 proteinopathies
- spinocerebellar ataxias
- Huntington disease
- hereditary spastic paraplegia
- clinically unclassifiable parkinsonism (CUP)
- Unverricht-Lundborg disease
prion diseases (not always included as neurodegenerative)
- Creutzfeldt-Jakob disease (sporadic, variant, familial, and iatrogenic)
- fatal familial insomnia
- Gerstmann-Straussler-Scheinker disease
- variably protease sensitive prionopathy