Clinical, pathological and genetic characteristics of Perry disease—new cases and literature review

Jarosław Dulski, Catalina Cerquera-Cleves, Lukasz Milanowski, Alexa Kidd, Emilia J. Sitek, Audrey Strongosky, Ana María Vanegas Monroy, Dennis W. Dickson, Owen A. Ross, Jolanta Pentela-Nowicka, Jarosław Sławek, Zbigniew K. Wszolek

Research output: Contribution to journalArticlepeer-review

Abstract

Background and purpose: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. Methods: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed. Results: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play. Conclusions: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.

Original languageEnglish (US)
Pages (from-to)4010-4021
Number of pages12
JournalEuropean Journal of Neurology
Volume28
Issue number12
DOIs
StatePublished - Dec 2021

Keywords

  • DCTN1 gene
  • dynactin
  • neurodegenerative disorder
  • parkinsonism
  • TDP-43

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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