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Brain. 2017 May 1;140(5):1371-1383. doi: 10.1093/brain/awx053.

Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson's disease.

Butcher NJ1,2, Marras C3,4, Pondal M3, Rusjan P5,6, Boot E6,7, Christopher L2,3,5,8, Repetto GM9, Fritsch R10, Chow EWC1,6, Masellis M11, Strafella AP2,3,4,5,8,12, Lang AE2,3,4,12,13, Bassett AS1,2,6,7,14,15.

Author information

1
Clinical Genetics Research Program and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
2
Institute of Medical Science, University of Toronto, Ontario, Canada.
3
Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital and the Edmond J. Safra Program in Parkinson's Disease Research, University of Toronto, Toronto, Ontario, Canada.
4
Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
5
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
6
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
7
The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, and Department of Psychiatry, University Health Network, Toronto, Ontario, Canada.
8
Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Hospital Network, University of Toronto, Toronto, Ontario, Canada.
9
Centre for Genetics and Genomics, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
10
Departamento de Psiquiatría y Salud Mental, Clínica Psiquiátrica Recoleta, Universidad de Chile, Santiago, Chile.
11
Sunnybrook Health Sciences Research Centre, Toronto, Ontario, Canada.
12
Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
13
Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
14
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
15
Division of Cardiology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.

Abstract

The recurrent 22q11.2 deletion is a genetic risk factor for early-onset Parkinson's disease. Adults with the associated 22q11.2 deletion syndrome (22q11.2DS) may exhibit phenotypes that could help identify those at highest risk and reveal disease trajectories. We investigated clinical and neuroimaging features relevant to Parkinson's disease in 26 adults: 13 with 22q11.2DS at genetic risk of Parkinson's disease (mean age = 41.5 years, standard deviation = 9.7), 12 healthy age and sex-matched controls, and a 22q11.2DS patient with l-DOPA-responsive early-onset Parkinson's disease. Neuroimaging included transcranial sonography and positron emission tomography using 11C-dihydrotetrabenazine (11C-DTBZ), a radioligand that binds to the presynaptic vesicular monoamine transporter. The 22q11.2DS group without Parkinson's disease demonstrated significant motor and olfactory deficits relative to controls. Eight (61.5%) were clinically classified with parkinsonism. Transcranial sonography showed a significantly larger mean area of substantia nigra echogenicity in the 22q11.2DS risk group compared with controls (P = 0.03). The 22q11.2DS patient with Parkinson's disease showed the expected pattern of severely reduced striatal 11C-DTBZ binding. The 22q11.2DS group without Parkinson's disease however showed significantly elevated striatal 11C-DTBZ binding relative to controls (∼33%; P < 0.01). Results were similar within the 22q11.2DS group for those with (n = 7) and without (n = 6) psychotic illness. These findings suggest that manifestations of parkinsonism and/or evolution to Parkinson's disease in this genetic at-risk population may include a hyperdopaminergic mechanism. Adequately powered longitudinal studies and animal models are needed to evaluate the relevance of the observed clinical and imaging phenotypes to Parkinson's disease and other disorders that are more prevalent in 22q11.2DS, such as schizophrenia.

KEYWORDS:

11C-DTBZ PET; 22q11.2 deletion syndrome; Parkinson’s disease; dopamine; neurotoxicity

PMID:
28369257
DOI:
10.1093/brain/awx053
[Indexed for MEDLINE]

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