@article{24f9b4330f43466bbc40c7c0e0f31809,
title = "Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2",
abstract = "Objective To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. Methods In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). Results 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). Conclusions Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing.",
author = "{International Research Group on 22q11.2DS-associated Parkinson's Disease} and Erik Boot and Butcher, {Nancy J.} and Sean Udow and Connie Marras and Mok, {Kin Y.} and Satoshi Kaneko and Barrett, {Matthew J.} and Paolo Prontera and Berman, {Brian D.} and Mario Masellis and Boris Dufournet and Karine Nguyen and Perrine Charles and Eug{\'e}nie Mutez and Teodor Danaila and Aur{\'e}lia Jacquette and Olivier Colin and Sophie Drapier and Michel Borg and Fiksinski, {Ania M.} and Elfi Vergaelen and Ann Swillen and Annick Vogels and Annika Plate and Claudia Perandones and Thomas Gasser and Kristien Clerinx and Fr{\'e}d{\'e}ric Bourdain and Kelly Mills and Williams, {Nigel M.} and Wood, {Nicholas W.} and Jan Booij and Lang, {Anthony E.} and Bassett, {Anne S.}",
note = "Funding Information: The majority of the work was undertaken at the Dalglish Family 22q Clinic for Adults in Toronto, Canada. This work was supported financially by the Physicians{\textquoteright} Services Incorporated Foundation (15-15; E.B.); the Canadian Institutes of Health Research (MOP 97,800 and 111238; A.S.B.); the National Institute of Mental Health (5U01MH101723; A.S.B. and E.B.); the University of Toronto McLaughlin Centre (A.S.B.); a Brain Canada Mental Health Training Award (N.J.B.); and the Dalglish Fellowship in 22q11.2 deletion syndrome awarded to E.B. The work was also supported by the Mauro Baschirotto Institute for Rare Diseases Foundation; the Karin och Sten Mortstedt CBD Solutions AB (K.Y.M.); the Weston Medical Trustees (K.Y.M.); the Chow Tai Fook Charity Foundation (K. Y.M.); the Welcome Trust (K.Y.M.); the Alzheimer{\textquoteright}s Research UK (K.Y.M.); the Innovation and Technology Commission of the Government of Hong Kong (K.Y.M.); the NIH (NIH/ NCATS Colorado CTSI Grant KL2 TR001080) (B.D.B.); the Dystonia Coalition (receives the majority of its support through NIH grant NS065701 from the Office of Rare Diseases Research in the National Center for Advancing Translational Science and National Institute of Neurological Disorders and Stroke) (B.D.B.); the Dana Foundation (B.D.B.); the Sunnybrook Foundation (M.M.); the Ontario Neurodegenerative Disease Research Initiative (M.M.); the Department of Medicine at Sunnybrook Health Sciences Centre (M.M.); the University of Toronto (M.M.); NIH/NINDS (1K23NS101096-01A1) (K.M.); and Fondecyt-Chile grant 1171014 (Gabriela M. Repetto). Part of this work was supported financially by a Medical Research Council/Wellcome Trust Strategic Award (WT089698/Z/09/Z) and grants from CBD Solutions and Parkinsons UK. Part of the work was undertaken at University College London Hospitals and University College London, who receive support from the Department of Health{\textquoteright}s NIHR Funding Information: Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by Wellcome Trust/COAF Partners. Funding Information: The majority of the work was undertaken at the Dalglish Family 22q Clinic for Adults in Toronto, Canada. This work was supported financially by the Physicians' Services Incorporated Foundation (15-15; E.B.); the Canadian Institutes of Health Research (MOP 97,800 and 111238; A.S.B.); the National Institute of Mental Health (5U01MH101723; A.S.B. and E.B.); the University of Toronto McLaughlin Centre (A.S.B.); a Brain Canada Mental Health Training Award (N.J.B.); and the Dalglish Fellowship in 22q11.2 deletion syndrome awarded to E.B. The work was also supported by the Mauro Baschirotto Institute for Rare Diseases Foundation; the Karin och Sten Mortstedt CBD Solutions AB (K.Y.M.); the Weston Medical Trustees (K.Y.M.); the Chow Tai Fook Charity Foundation (K. Y.M.); the Welcome Trust (K.Y.M.); the Alzheimer's Research UK (K.Y.M.); the Innovation and Technology Commission of the Government of Hong Kong (K.Y.M.); the NIH (NIH/ NCATS Colorado CTSI Grant KL2 TR001080) (B.D.B.); the Dystonia Coalition (receives the majority of its support through NIH grant NS065701 from the Office of Rare Diseases Research in the National Center for Advancing Translational Science and National Institute of Neurological Disorders and Stroke) (B.D.B.); the Dana Foundation (B.D.B.); the Sunnybrook Foundation (M.M.); the Ontario Neurodegenerative Disease Research Initiative (M.M.); the Department of Medicine at Sunnybrook Health Sciences Centre (M.M.); the University of Toronto (M.M.); NIH/NINDS (1K23NS101096-01A1) (K.M.); and Fondecyt-Chile grant 1171014 (Gabriela M. Repetto). Part of this work was supported financially by a Medical Research Council/Wellcome Trust Strategic Award (WT089698/Z/09/Z) and grants from CBD Solutions and Parkinsons UK. Part of the work was undertaken at University College London Hospitals and University College London, who receive support from the Department of Health's NIHR Biomedical Research Centres funding streams. A.S.B. holds the Dalglish Chair in 22q11.2 Deletion Syndrome at the Toronto General Hospital. The funding agencies had no further role in study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. Publisher Copyright: Copyright {\textcopyright} 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",
year = "2018",
doi = "10.1212/WNL.0000000000005660",
language = "English (US)",
volume = "90",
pages = "E2059--E2067",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "23",
}