Perry syndrome G20.-

Perry Syndrome is a rare, autosomal-dominantly inherited neurodegenerative disorder characterized by rapidly progressive, early-onset parkinsonism, central hypoventilation, weight loss, insomnia, and depression.

The prevalence is unknown. To date, 53 cases have been described from 11 families in Canada, the United States, the United Kingdom, France, Turkey, and Japan.

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

Perry syndrome begins on average at age 48 (range 35-61 years) and is manifested by parkinsonism (akinetic-rigid and rather symmetrical), psychiatric changes in the form of depression, lethargy, withdrawal, apathy, and personality changes, and sleep problems. The usual duration of Perry syndrome is about 5 years, with severe weight loss and central hypoventilation seen late in the course of the disease. Marked autonomic dysfunction has been reported in one family from Japan. Patients are often bedridden or wheelchair-bound, as motor skills may be severely limited in the later stages of the disease.

The diagnosis is based on clinical findings of early-onset parkinsonism combined with depression, weight loss, and hypoventilation, and is confirmed by molecular genetic testing that identifies a mutation in the DCTN1 gene.

Perry syndrome is not curable. Symptomatic treatment requires a multidisciplinary team. To treat parkinsonism, patients receive dopaminergic therapy, usually with levodopa/carbidopa. Response to levodopa may be erratic or absent, but high doses (>2 g) have reduced symptoms in several patients. Patients with hypoventilation require ventilator support (invasive or noninvasive), especially at night. Respiratory function should be monitored continuously. Z

Prognosis is poor. Death occurs due to respiratory failure or suicide, or in some cases may be sudden and unexplained. Ventilation support may prolong survival with acceptable quality of life.

1. Caroppo P et al (2014) DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes. JAMA Neurol 71: 208-215.
2. Farrer MJ et al (2009) DCTN1 mutations in Perry syndrome. Nature Genet 41: 163-165.
3. Perry TL et al (1975) Hereditary mental depression and parkinsonism with taurine deficiency. Arch. Neurol 32: 108-113.
4. Perry TL et al (1990) Dominantly inherited apathy, central hypoventilation, and parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. Neurology 40: 1882-1887.