Page 37 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Parkinsonism in GNDs
ten reported patients were 22q11.2 deletion syndrome and Down syndrome,
respectively. Between five and ten patients were reported for Klinefelter
syndrome. Forty-nine patients without genetic confirmation but with a
biochemical or clinical diagnosis were included, with five or more patients
reported for: Rett syndrome, neurofibromatosis type I, Down syndrome, and
glutaric aciduria type 1. Less than five cases were reported for another 47
GNDs (see Supplementary Figure S2).
Thirteen of 422 patients (3.1%) were reported to have an additional genetic
variant of potential clinical relevance for the development of parkinsonism,
annotated in Figure 1 and Supplementary Figure S2.
Parkinsonian features
The median age at onset of motor symptoms, available for 349 of 422
patients, was 26 (range 0-66) years. For those with motor symptoms
reported, rigidity was the most prevalent parkinsonian feature after
bradykinesia, being present in 330 of 346 patients (95.4%). Rest tremor
was seen in 218 of 355 (61.4%), postural instability in 138 of 179 (77.1%),
asymmetry in 176 of 212 (83.0%), and progression of motor symptoms in
239 of 267 (89.5%) patients with data. Reduced DAT-binding was seen in the
majority of the 39 GNDs with available dopaminergic imaging results, but
not in Rett syndrome, Dravet syndrome (SCN1A), dihydropteridine reductase
deficiency and CLTC. A clear and beneficial response to antiparkinsonian
medication was reported in 187 of 262 patients (71.4%). GNDs with
questionable or no response to antiparkinsonian medication in most cases
were Rett syndrome, Dravet syndrome (SCN1A), phosphoglycerate kinase
deficiency, dystonia 16, Leigh syndrome, and Menkes disease. Levodopa-
induced dyskinesia was described in 74 of 157 patients (47.1%).
Neurological and psychiatric comorbidity
Intellectual functioning was reported for 320 of 422 patients (75.8%), with
intellectual disability present in 193 patients (60.3%). Cognitive decline
or dementia was reported in 70 patients (16.6%). In 103 patients (24.4%)
psychiatric comorbidity was present, such as depression, anxiety or
psychosis. An additional neurologic disorder, not including dementia, was
reported in 256 (60.7%) of 422 patients: dystonia in 128 (30.3%), epilepsy/
seizures in 112 (26.5%) and ataxia in 38 patients (9.0%).
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