Clinicopathological characterisation of the first Australian family with the p.G51D SNCA mutation.
Peter K Panegyres, John B Kwok, Reimar Junckerstorff
✦ AI-curated · Sources linked
Case in brief
A family carrying the p.G51D SNCA mutation was identified through a community study of young-onset dementia. The proband developed parkinsonism at 38, followed by cognitive difficulties at 41 that progressed to dementia. Neuropathological examination showed Lewy bodies in the substantia nigra and locus coeruleus, with extensive involvement of the neocortex, brainstem, basal forebrain and limbic regions. Two sisters also developed parkinsonism and cognitive decline at different ages; one had recently developed dementia. A 27-year-old relative carried the mutation and had subtle thumb tremor.
What made this case unusual
The family showed variable age at onset and prominent cognitive, dystonic and neuropsychiatric manifestations alongside diffuse neocortical Lewy body pathology, broadening the reported phenotype associated with p.G51D SNCA.
Diagnostic / clinical pearl
In a family with early-onset parkinsonism and cognitive decline, consider genetic evaluation for SNCA mutations; p.G51D may be associated with variable onset and extensive Lewy body disease.