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

Butcher, Nancy J.; Marras, Connie; Pondal, Margarita; Rusjan, Pablo; Boot, Erik; Christopher, Leigh; Repetto, Gabriela M.; Fritsch, Rosemarie; Chow, Eva W.C.; Masellis, Mario; Strafella, Antonio P.; Lang, Anthony E.; Bassett, Anne S.

doi:10.1093/brain/awx053

Cited by 44 publications

(63 citation statements)

References 67 publications

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“…There is incomplete penetrance for PD in 22q11.2DS, as in other populations at genetic risk for PD. The sole prevalence estimate available reported 5.9% with PD in a cohort of 159 adults with 22q11.2DS aged 35 to 64 years . Additional genetic and environmental factors that contribute to the increased PD risk in this group of patients are yet to be determined.…”

Section: Microdeletion 22q112: a Genetic Risk Factor For Pdmentioning

confidence: 98%

“…In addition to PD, parkinsonism not meeting criteria for PD may be more common in individuals with 22q11.2DS than in the general population . Molecular imaging, particularly dopamine transporter (DAT) imaging, may be helpful to distinguish PD from nondegenerative parkinsonism .…”

Section: Diagnostic Challengesmentioning

confidence: 99%

“…Indeed, blood samples from individuals with 22q11.2DS have shown reduced COMT expression and enzyme activity levels and decreased levels of the dopamine metabolite, homovanillic acid . Moreover, a study with PET and 11 C‐dihydrotetrabenazine ( 11 C‐DTBZ), a radioligand that binds to the presynaptic vesicular monoamine transporter, reported elevated binding of 11 C‐DTBZ in the striatum in individuals with 22q11.2DS over age 30 years but without PD, compared to healthy age‐ and sex‐matched controls, indicating a hyperdopaminergic state …”

Section: Managementmentioning

confidence: 99%

“…The sole prevalence estimate available reported 5.9% with PD in a cohort of 159 adults with 22q11.2DS aged 35 to 64 years. 10 Additional genetic and environmental factors that contribute to the increased PD risk in this group of patients are yet to be determined. A whole-genome sequencing pilot study in patients with 22q11.2DS showed nominal enrichment in the PD cases of 9,10 To be determined Other movement disorders (e.g., myoclonic disorders) 9,[11][12][13] To be determined Functional neurological disorder 6 To be determined Psychiatric Attention deficit and hyperactivity disorder (pediatric history) 8 >30% Anxiety disorders 8,17 30% Schizophrenia 8,17 20% to 25% Cognitive a Learning disabilities 5 >90% Intellectual disabilities 5 35% Cognitive deterioration 14 To be determined Sensory system…”

Section: Microdeletion 22q112: a Genetic Risk Factor For Pdmentioning

confidence: 99%

“…The mean age at PD onset is relatively young (∼40 years) in patients with 22q11.2DS In addition to PD, parkinsonism not meeting criteria for PD and other movement disorders may be more common in 22q11.2DS than in the general population Dopaminergic imaging may be helpful in the differentiation of PD from nondegenerative 22q11.2DS‐associated parkinsonism …”

mentioning

confidence: 99%

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22q11.2 Deletion Syndrome–Associated Parkinson's Disease

Boot

Bassett

Marras

2018

Movement Disord Clin Pract

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Background22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early‐onset Parkinson's disease (PD).MethodsWe review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications.Results22q11.2DS‐associated PD is responsible for approximately 0.5% of early‐onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS‐associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS‐associated PD show a good response to levodopa.ConclusionsFurther recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease‐modifying treatments.

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Section: Microdeletion 22q112: a Genetic Risk Factor For Pdmentioning

confidence: 98%

Section: Diagnostic Challengesmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

Section: Microdeletion 22q112: a Genetic Risk Factor For Pdmentioning

confidence: 99%

mentioning

confidence: 99%

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22q11.2 Deletion Syndrome–Associated Parkinson's Disease

Boot

Bassett

Marras

2018

Movement Disord Clin Pract

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Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: An overview and case series

Butcher

Boot

Lang

et al. 2018

American J of Med Genetics Pt A

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Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at elevated risk of developing treatable psychiatric and neurological disorders, including anxiety disorders, schizophrenia, seizures, and movement disorders, often beginning in adolescence or early to mid-adulthood. Here, we provide an overview of neuropsychiatric features associated with 22q11.2DS in adulthood. Results of a new case series of 13 individuals with 22q11.2DS and catatonic features together with 5 previously reported cases support a potential association of this serious psychomotor phenotype with the 22q11.2 deletion. As in the general population, catatonic features in 22q11.2DS occurred in individuals with schizophrenia, other psychotic and non-psychotic psychiatric disorders, and neurological disorders like Parkinson's disease. We place the results in the context of an updated review of catatonia in other genetic conditions. The complex neuropsychiatric expression and risk profile of 22q11.2DS highlights the need to consider co-morbid factors and provide care tailored to the individual patient. The results reinforce the need for periodic monitoring for the emergence of psychiatric and neurological manifestations including catatonic features. Pending further research, enhanced recognition and informed anticipatory care promise to facilitate the early diagnosis that allows for timely implementation and optimization of effective treatments.

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