TY - JOUR
T1 - Clinical, pathological and genetic characteristics of Perry disease—new cases and literature review
AU - Dulski, Jarosław
AU - Cerquera-Cleves, Catalina
AU - Milanowski, Lukasz
AU - Kidd, Alexa
AU - Sitek, Emilia J.
AU - Strongosky, Audrey
AU - Vanegas Monroy, Ana María
AU - Dickson, Dennis W.
AU - Ross, Owen A.
AU - Pentela-Nowicka, Jolanta
AU - Sławek, Jarosław
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
Jaroslaw Dulski: employment, Medical University of Gdansk, Copernicus PL Ltd, MJ Jarosław Dulski; honoraria, VM Media Ltd, Radosław Lipiński 90 Consulting, Ipsen. Catalina Cerquera‐Cleves: advisory boards, Legrand, Zambon and Biopas; employment, San Ignacio Hospital, Clínica Universitaria Colombia; honoraria, Legrand, Zambon and Biopas. Lukasz Milanowski: employment, Medical University of Warsaw, Brodno Mazovia Hospital; grants, Polish National Agency for Academic Exchange Iwanowska's Fellowship PPN/IWA/2018/1/00006/U/00001/01, the APDA and the Haworth Family Professorship in Neurodegenerative Diseases fund. Alexa Kidd: employment, Clinical Genetics NZ Limited, Hillmorton Hospital Christchurch; contracts, none except employment contracts for the above jobs. Emilia J. Sitek: consultancies, Cogstate Ltd; employment, Medical University of Gdansk, Copernicus PL Ltd; contracts, Gdańskie Centrum Zdrowia Ltd, University of Gdansk; honoraria, Medical Tribune, VM Media Ltd, Wydawnictwo Czelej Ltd, Sopockie Centrum Terapii Poznawczo‐Behawioralnej Michał Kuchczyński, Radosław Lipiński 90 Consulting, Medical University in Lodz; royalties, Wydawnictwo Harmonia Józef Częścik. Audrey Strongosky: employment, Mayo Clinic. Ana María Vanegas Monroy: employment, Clinica Universitaria Colombia. Dennis W. Dickson: employment, Mayo Clinic; grants, NIH (U19 AG069701, P30 AG062677, U54 NS100693, U54 NS110435, UH3 NS104095, R01 AG062348). Owen A. Ross: employment Mayo Clinic; grants, NIH/NINDS U54‐NS100693, UG3‐NS104095, U54‐ NS110435, DOD (W81XWH‐17‐1‐0249), the Michael J. Fox Foundation and American Parkinson Disease Association Center for Advanced Research. Jolanta Pentela‐Nowicka: employment, Medical University of Lodz; contracts, Amgen, Johnson&Johnson (PI). Jarosław Sławek: consultancies, Allergan, Abbvie, Ipsen, Everpharma, Merz, Novartis, Biogen, Roche, TEVA; employment, Medical University of Gdansk, Copernicus PL Ltd; contracts, Allergan, Abbvie, Ipsen, Everpharma, Merz, Novartis, Biogen, Roche, TEVA; honoraria, Allergan, Abbvie, Ipsen, Everpharma, Merz, Novartis, Biogen, Roche, TEVA, Polish Neurological Society co‐editor‐in‐chief of . Zbigniew K. Wszolek: intellectual property rights, Mayo Clinic and ZKW have a financial interest in technologies entitled “Identification of Mutations in PARK8, a Locus for Familial Parkinson's Disease” and “Identification of a Novel LRRK2 Mutation, 6055G>A (G2019S), Linked to Autosomal Dominant Parkinsonism in Families from Several European Populations”. Those technologies have been licensed to a commercial entity, and to date ZKW has received royalties <$1.500 through Mayo Clinic in accordance with its royalty sharing policies. Consultancies: Vigil Neuroscience Inc.; Advisory Boards, Vigil Neuroscience Inc.; employment, Mayo Clinic Florida; honoraria, Polish Neurological Society co‐editor‐in‐chief of ; grants, NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and the Albertson Parkinson's Research Foundation. He serves as PI or Co‐PI on Biohaven Pharmaceuticals Inc. (BHV4157‐206 and BHV3241‐301), Neuraly Inc. (NLY01‐PD‐1) and Vigil Neuroscience Inc. (VGL101‐01.001) grants. Neurologia i Neurochirurgia Polska Neurologia i Neurochirurgia Polska
Funding Information:
Jaroslaw Dulski: employment, Medical University of Gdansk, Copernicus PL Ltd, MJ Jaros?aw Dulski; honoraria, VM Media Ltd, Rados?aw Lipi?ski 90 Consulting, Ipsen. Catalina Cerquera-Cleves: advisory boards, Legrand, Zambon and Biopas; employment, San Ignacio Hospital, Cl?nica Universitaria Colombia; honoraria, Legrand, Zambon and Biopas. Lukasz Milanowski: employment, Medical University of Warsaw, Brodno Mazovia Hospital; grants, Polish National Agency for Academic Exchange Iwanowska's Fellowship PPN/IWA/2018/1/00006/U/00001/01, the APDA and the Haworth Family Professorship in Neurodegenerative Diseases fund. Alexa Kidd: employment, Clinical Genetics NZ Limited, Hillmorton Hospital Christchurch; contracts, none except employment contracts for the above jobs. Emilia J. Sitek: consultancies, Cogstate Ltd; employment, Medical University of Gdansk, Copernicus PL Ltd; contracts, Gda?skie Centrum Zdrowia Ltd, University of Gdansk; honoraria, Medical Tribune, VM Media Ltd, Wydawnictwo Czelej Ltd, Sopockie Centrum Terapii Poznawczo-Behawioralnej Micha? Kuchczy?ski, Rados?aw Lipi?ski 90 Consulting, Medical University in Lodz; royalties, Wydawnictwo Harmonia J?zef Cz??cik. Audrey Strongosky: employment, Mayo Clinic. Ana Mar?a Vanegas Monroy: employment, Clinica Universitaria Colombia.
Publisher Copyright:
© 2021 European Academy of Neurology
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - DCTN1 gene
KW - TDP-43
KW - dynactin
KW - neurodegenerative disorder
KW - parkinsonism
UR - http://www.scopus.com/inward/record.url?scp=85113583682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113583682&partnerID=8YFLogxK
U2 - 10.1111/ene.15048
DO - 10.1111/ene.15048
M3 - Article
C2 - 34342072
AN - SCOPUS:85113583682
VL - 28
SP - 4010
EP - 4021
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
IS - 12
ER -