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

Abstract

ObjectiveTo 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.MethodsIn 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).Results22q11.2DS 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%).ConclusionsMajor 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.

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

“…Standard treatments for PD are recommended for 22q11.2DS‐associated PD. The largest study to date on 22q11.2DS‐associated PD showed a positive response to pharmacological replacement of dopamine with l ‐dopa in the majority of the patients (>90%) . The response to other medications in this study was reported for such a small number of patients that no conclusions could be drawn.…”

“…PD in 22q11.2DS appears largely indistinguishable from idiopathic PD with respect to major clinical PD features . In 22q11.2DS‐associated PD, the male‐to‐female ratio (∼2.5:1) shows a male predominance, motor onset is asymmetric in most cases, and cardinal motor features (i.e., bradykinesia, rigidity, and tremors) predominate in the early stages.…”

“…However, there are also some differences from idiopathic PD. For example, age at PD onset in 22q11.2DS is often earlier with mean age 39.5 ± 8.5 years (range, 18–58), and >70% having onset < 45 years of age . Features that appear to be more common in 22q11.2DS than in idiopathic PD include early dystonia, history of seizures, and neuropsychiatric symptoms (e.g., psychosis and anxiety) preceding PD onset .…”

“…For example, Wilson's disease was considered, but not confirmed, in at least 4 reported patients with 22q11.2DS and abnormal movements . Use of antipsychotic medications may delay the diagnosis of PD significantly, given that parkinsonism may be assumed to be drug induced . Other medications that may be associated with parkinsonism, including selective serotonin reuptake inhibitors, are also frequently taken by individuals with 22q11.2DS.…”

“…Molecular imaging, particularly dopamine transporter (DAT) imaging, may be helpful to distinguish PD from nondegenerative parkinsonism . Typical findings of reduced striatal DAT binding has been reported in several individuals with 22q11.2DS‐associated parkinsonism . However, it is uncertain whether DAT binding levels in individuals with 22q11.2DS at a young age may be increased compared to the general population, possibly complicating the interpretation for some 22q11.2DS individuals with parkinsonism and normal imaging results.…”