Objective: We describe an unusual case of parkinsonism in a 45-year-old male with Fragile X syndrome and XYY syndrome.

Background: Fragile X syndrome (FXS) is a genetic disorder within the spectrum of disorders caused by CGG repeat expansion in the FMR1 gene. Depending on the number of repeats and on methylation of the repeat region, FMR1 disorders may manifest as FXS (in cases with >200 repeats) or as fragile-X-associated tremor/ataxia syndrome (FXTAS; 55-200 repeats), with differing clinical presentations. FXS typically involves onset in infancy with developmental delay, intellectual disability, stereotypies and behavioural abnormalities. FXTAS typically presents with late-onset (median in the 7^th decade) progressive cerebellar ataxia and tremor, followed by cognitive impairment. XYY syndrome is a chromosome abnormality with disomy of chromosome Y, characterised by tall stature and mild delays in motor and language development; movement disorders (tremor, ataxia, dysdiadochokinesis) have been described in a subset of XYY syndrome cases. Parkinsonism has been reported in FXTAS but is not considered to be a typical feature of FXS and is not known to be associated with XYY syndrome.

Method: We report the clinical and diagnostic findings in a 45-year-old male who was diagnosed with FXS and XYY syndromes in his childhood and presented with progressive parkinsonism.

Results: The patient complained of reduced fine motor skills and progressive global slowing over the last few years. He had been treated with risperidone for psychiatric symptoms. After switching to clozapine, he still presented with a slightly asymmetric (left > right) akinetic-rigid syndrome, hypomimia, postural tremor and dysarthrophonia. Cerebellar signs were not present. Cerebral MRI showed symmetrical cortical, insular and thalamic atrophy. DaT-SPECT revealed bilateral dopaminergic neurodegeneration (right > left). After treatment with levodopa, the patient reported an improvement of fine motor skills and gait, and a mild improvement of the parkinsonism could be observed.

Conclusion: Parkinsonism (both Parkinson´s disease and atypical parkinsonism) is increasingly recognised as a minor feature in FXTAS but has only been reported very rarely in FXS. Our case highlights that parkinsonism can be improved with levodopa and by avoiding classic antipsychotics. We aim to investigate the patient for FMR1 repeat mosaicism, which may explain some “intermediate phenotypes”, such as our case.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonism-in-combined-fragile-x-and-xyy-syndromes-a-case-report/