Perry syndrome

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.

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.

The syndrome was first described in a Canadian family by Thomas L Perry and colleagues in their 1975 seminal case series 8.

Neurodegenerative diseases

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.

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Article information

rID: 73240
Section: Syndromes
Tag: cases
Synonyms or Alternate Spellings:

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