Age-Related Parkinsonian Signs in Microdeletion 22q11.2

Abstract

Background: The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition.

Objectives: We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD.

Methods: We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia.

Results: Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%.

Conclusions: Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: 22q11.2 deletion syndrome; Parkinson's disease; aging; parkinsonism; wearable sensors.

Figure 1

Scatterplots of the relationship between age and MDS‐UPDRS part III, scores (A‐C), and averaged standardized scores of cycle/stride velocity, duration, and amplitude as assessed with electronic 3D motion‐tracker technology (D‐F). Orange dot symbols indicate adults with 22q11.2DS. Black dot symbols indicate the 7 individuals meeting criteria for the presence of parkinsonism. Open dots (orange or black) indicate those with no history of psychotic illness, and filled dots those with such history. Blue ‘x’ symbols indicate healthy controls. (A‐C) None of the controls met MDS‐UPDRS criteria for bradykinesia, rigidity, or rest tremor; data not shown. Spearman's rank order correlations are shown to the left of the plots. (D‐F) Horizontal black lines represent the mean scores (z‐score=0) for the total study sample (see Supplementary Methods for details). Pale blue background indicates the range of results for the controls. We note, however, that in the absence of population‐based normative data, z‐scores were based on the total study sample, with the majority of participants having a 22q11.2 deletion. Pearson correlation coefficients are shown to the left of the plots. Linear regression models did not show a statistically significant interaction between age and study group (controls vs. 22q11.2DS) on the averaged standardized z‐scores, except for the bradykinesia component duration (P = 0.03). [Color figure can be viewed at wileyonlinelibrary.com]