Objective: Case presentation of a novel genetic variant associated with parkinsonism.

Background: Parkinsonism is a clinical syndrome characterized by a combination of bradykinesia, rigidity, tremor and postural instability. It is associated with various disease processes. We present a case of a relatively rapid progressive parkinsonism associated with a novel genetic variant.

Method: Case study of a female patient presenting with parkinsonism.

Results: The patient was a 51-year-old female from Afghanistan, born of consanguineous parents. Her mother had gait difficulties about which further information is not available. The patient presented with a 3-year history of progressively worsening parkinsonism, dysarthria, gait impairment with multiple falls requiring use of a wheelchair. She had mild clumsiness, but no gross ataxia and mild autonomic dysfunction present as orthostatic hypotension and constipation. MRI brain demonstrated significant cerebellar atrophy and extrapyramidal findings including putamen atrophy. FDG PET showed non-quantitatively significant reduced FDG uptake involving bilateral cerebellum. Electrophysiological studies demonstrated length-dependent sensory axonal polyneuropathy. Serum and CSF testing was unremarkable including for paraneoplastic/autoimmune antibodies. She had elevated CSF neurofilament light chains. Genetic testing identified a homozygous missense variant CWF19L1c.969G>T,p.(Gln323His) with autosomal recessive inheritance which is a variant of uncertain significance not previously reported in the literature. The CWF19L1 encodes a member of the CWF19 protein family and not much is known about this gene. Variants in CWF19L1 have been associated with spinocerebellar ataxia and mild cognitive disability. She had minimal response to levodopa and a dopamine agonist.

Conclusion: This case illustrates a patient with a novel gene variant associated with relatively rapid progressive parkinsonism, gait impairment, dysarthria and mild clumsiness and autonomic dysfunction.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-genetic-variant-associated-with-parkinsonism/