This paper reports the fifth French case of fatal familial insomnia characterized by a mutation at codon 178 of the prion protein gene and by heterozygosity (Met/Val) at codon 129. The clinical picture included cerebellar ataxia, dysautonomia and a frontal lobe syndrome. Prion protein gene analysis was performed to exclude a diagnosis of Creutzfeldt-Jakob disease; it confirmed a diagnosis of fatal familial insomnia.

Neuropathology showed unusual changes including severe neuronal loss in the inferior olive and dentate nucleus and the absence of obvious thalamic lesions. Moreover, spongiform changes were moderate in the superior temporal and occipital cortices. There was no spongiform change in the frontal cortex. Abnormal prion protein (PrPres) was mainly present in the parietal cortex.

Molecular genetic studies of the PRNP gene should be performed in patients who present with a cerebellar ataxia of equivocal origin.

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