Page 37 - Demo

Parkinsonism in GNDs352ten 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 featuresThe 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. Levodopainduced dyskinesia was described in 74 of 157 patients (47.1%). Neurological and psychiatric comorbidityIntellectual 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%).