Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2.

Neurology 2018 06 11;90(23):e2059-e2067. Epub 2018 May 11.

From The Dalglish Family 22q Clinic for Adults and Department of Psychiatry (E.B., A.M.F., A.S.B.), Toronto General Research Institute (A.S.B.), and Division of Cardiology, Department of Medicine (A.S.B.), University Health Network, Toronto, Canada; De Hartekamp Groep (E.B.), Centre for People with Intellectual Disability, Haarlem; Department of Nuclear Medicine (E.B., J.B.), Academic Medical Center, Amsterdam, the Netherlands; Clinical Genetics Research Program and Campbell Family Mental Health Research Institute (N.J.B., A.M.F., A.S.B.), Centre for Addiction and Mental Health, Toronto; Institute of Medical Science (N.J.B., M.M., A.E.L., A.S.B.), Division of Neurology, Department of Medicine (C.M., M.M., A.E.L.), and Department of Psychiatry (A.S.B.), University of Toronto; Deer Lodge Movement Disorders Centre (S.U.); Section of Neurology (S.U.), Division of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease Research (C.M., A.E.L.), Toronto Western Hospital and University of Toronto, Canada; Department of Molecular Neuroscience (K.Y.M., N.W.W.), UCL Institute of Neurology, London, UK; Department of Neurology (S.K.), Kansai Medical University, Osaka, Japan; Department of Neurology (M.J.B.), University of Virginia School of Medicine, Charlottesville; Medical Genetics Unit (P.P.), Perugia University Hospital, Italy; Department of Neurology (B.D.B.), University of Colorado Anschutz Medical Campus, Aurora; Neurology Section (B.D.B.), VA Eastern Colorado Health Care System, Denver; Cognitive & Movement Disorders Clinic and Hurvitz Brain Sciences Research Program (M.M.), Sunnybrook Health Sciences Centre, Toronto, Canada; Departments of Clinical Neurosciences (Movement Disorders) (B.D.) and Genetics (Neurogenetics) (K.N.), Timone University Hospital (AP-HM), Provence-Alpes-Côte d'Azur; Aix-Marseille University (B.D., K.N.), Marseille; Department of Genetics (Neurogenetics) (P.C., A.J.), Pitié-Salpêtrière University Hospital; Sorbonne University (P.C., A.J.), Paris; Department of Neurosciences (Movement Disorders) (E.M.), Lille University Hospital; Lille University (E.M.); Department of Neurology (Movement Disorders) (T.D.), Pierre Wertheimer University Hospital, Lyon; Marc Jeannerod Center for Cognitive Neurosciences (T.D.), Lyon-1 University; Department of Neurology (Movement Disorders) and Clinical Investigation Center (Clinical and Experimental Neurosciences) (O.C.), Poitiers University Hospital; Department of Neurology (Movement Disorders) (S.D.), Rennes University Hospital; Rennes-1 University (S.D.); Department of Clinical Neurosciences (Movement Disorders) (M.B.), Nice University Hospital, France; Department of Psychiatry (A.M.F.), Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands; Center for Human Genetics (E.V., A.S., A.V.), University Hospital Leuven; Department of Human Genetics (A.S.), KU Leuven, Belgium; Department of Neurology (A.P.), University of Munich, Germany; Scientific and Technological Coordination Unit of the ANLIS Directorate (C.P.), National Administration of Laboratories and Institutes of Health, Argentina; Department of Neurodegenerative Diseases (T.G.), Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen; German Center for Neurodegenerative Diseases (DZNE) (T.G.); Department of Neurology (K.C.), AZ Turnhout, Antwerp, Belgium; Neurology Unit and Stroke Center (F.B.), Hôpital Foch, Suresnes, France; Movement Disorder Division (K.M.), Johns Hopkins University, Baltimore, MD; and Psychological Medicine and Clinical Neurosciences (N.M.W.), MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff University, UK.

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, = 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.

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http://dx.doi.org/10.1212/WNL.0000000000005660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993183PMC
June 2018
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