Emerging insight in genetics and therapies in young-onset Parkinson’s disease (YOPD): a comprehensive review

AI Summary

Distinct genetic mutations (PARK2, PINK1, DJ-1, SNCA, LRRK2, GBA) drive YOPD pathogenesis and modulate clinical course and prognosis.
YOPD presents with rigidity, dystonia, early motor fluctuations and heightened psychiatric symptoms, causing substantial psychosocial burden and reduced quality of life.
Advanced therapies such as deep brain stimulation and apomorphine infusion show benefit; neuroimaging improves diagnosis but YOPD-specific evidence remains limited, requiring personalised multidisciplinary care.

J Neurol. 2026 Jun 5;273(7):370. doi: 10.1007/s00415-026-13914-x.

ABSTRACT

Young-onset Parkinson’s disease (YOPD), defined as Parkinson’s disease (PD) with onset between 21 and 50 years of age, represents 3-7% of all PD cases. YOPD is characterized by distinct genetic profiles, unique clinical manifestations, psychosocial challenges, and treatment responses compared to late-onset PD. Genetic mutations in PARK2, PINK1, DJ-1, SNCA, LRRK2, and GBA significantly contribute to the disease pathogenesis, influencing clinical outcomes and disease progression. Clinically, YOPD patients often present with rigidity, dystonia, and early motor fluctuations, alongside heightened psychiatric manifestations, significantly impacting quality of life. Advanced therapies, such as deep brain stimulation (DBS) and continuous subcutaneous apomorphine infusion (CSAI), offer substantial clinical benefit, although data specific to YOPD remain limited. Neuroimaging advancements provide insight into structural and functional brain alterations distinct to YOPD, facilitating earlier and more accurate diagnosis. This review synthesizes current knowledge on genetics, clinical features, psychosocial impacts, neuroimaging, and therapeutic approaches, underscoring the necessity for personalized multidisciplinary management strategies for YOPD.

PMID:42247186 | DOI:10.1007/s00415-026-13914-x

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