Progressive Supranuclear Palsy-Primary Lateral Sclerosis Overlap Syndrome in a Patient with a CYLD Variant

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome characterized by progressive axial rigidity, vertical gaze palsy, dysarthria, and dysphagia. This report describes a case of PSP-primary lateral sclerosis overlap syndrome associated with a CYLD gene variant.

We describe the case of a 59-year-old male patient who presented with slowing of movements and hypophonic speech. Neurological examination revealed hypomimia, dysarthric and hypophonic speech, restricted upward gaze, slow saccadic eye movements, rigidity and bradykinesia in all extremities, axial rigidity, brisk deep tendon reflexes, bilateral positive Hoffman's sign, and bilateral extensor plantar responses. Brain MRI showed the "hummingbird sign" accompanied by bilateral cortico-spinal tract hyperintensity. MEP studies showed impaired excitability and conduction in the corticomotor system. Molecular genetic analysis identified a heterozygous G107A (c.320G>A; p.Gly107Asp) missense variant in the CYLD gene.

Based on these findings, a diagnosis of PSP-Primary Lateral Sclerosis overlap syndrome was made. The contribution of the identified CYLD variant to this complex phenotype and its role in the neurodegenerative disease spectrum warrant further investigation.