Psychiatric Manifestations of Mutations.

Background: Biallelic mutations in were identified as the cause of Kufor-Rakeb disease, a pallido-pyramidal syndrome characterized by young-onset dystonia-parkinsonism with vertical supranuclear gaze palsy, spasticity, and cognitive decline. The phenotypic spectrum has broadened since, but predominantly psychiatric or behavioral manifestations have not been highlighted.

Cases: Here we report the clinical, radiological, and genetic findings in 2 unrelated patients with mutations. One patient had a prominent behavioral (autistic spectrum) presentation and the other a psychiatric (paranoid psychosis) presentation. Both had additional features, such as delayed milestones, ataxia, pyramidal signs, upgaze restriction, or impaired cognition to varying extent, but these were partly subtle or developed later in the disease course.

Conclusion: Prominent behavioral or psychiatric features can be the first or most prominent manifestation of -related disease. They may be a diagnostic clue in patients with ataxia, spasticity, or parkinsonism and may require an interdisciplinary neurological and psychiatric treatment approach.