Objective: To describe the clinical and genetic characteristics of patients with childhood-onset parkinsonism associated with pyramidal signs.

Background: The coexistence of parkinsonism and pyramidal signs in childhood is uncommon and represents a complex clinical phenotype. This combination may obscure the underlying diagnosis and is increasingly recognized in association with rare neurogenetic disorders.

Method: We conducted a retrospective review of four patients with childhood-onset parkinsonism associated with pyramidal signs evaluated at a tertiary pediatric movement disorders center. Clinical, neuroimaging, and genetic data were analyzed.

Results: Four patients with childhood- or adolescent-onset parkinsonism and pyramidal signs were identified, each with a distinct genetic etiology. One patient with a pathogenic variant in SPG11 presented with rapidly progressive gait disturbance, bradykinesia, rigidity, dystonia, and pyramidal signs. A second patient with a NUS1 mutation developed early-onset action tremor followed by parkinsonism and hyperreflexia. A third patient with a variant in IRF2BPL presented with progressive spastic paraparesis followed by parkinsonian features and tremor. The fourth patient, carrying compound heterozygous pathogenic variants in ATP13A2, developed adolescent-onset parkinsonism with dysarthria, bradykinesia, vertical gaze palsy, spasticity, dystonia, and sensory-motor axonal neuropathy, consistent with Kufor-Rakeb syndrome. Neuroimaging findings included cerebral and cerebellar atrophy in this patient. Across the series, the coexistence of parkinsonian features and pyramidal signs was a key clinical clue prompting genetic investigation.

Conclusion: The coexistence of parkinsonism and pyramidal signs in young patients should raise suspicion for underlying neurogenetic disorders. Early recognition of this phenotype may guide targeted genetic testing and improve diagnostic accuracy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/childhood-onset-parkinsonism-with-prominent-pyramidal-signs-a-complex-neurogenetic-phenotype/