Objective: To comprehensively characterize demographic, genetic, and phenotypic features in individuals with autosomal recessive Parkinson’s disease (PD), leveraging individual-level data from published literature.

Background: In light of emerging targeted therapies for genetic PD, a detailed understanding of genotype-phenotype relationships is becoming increasingly important. This MDSGene (https://www.mdsgene.org/) literature update focuses on pathogenic variants in the autosomal recessive genes PRKN, PINK1, and PARK7, which are well-established causes of early-onset PD.

Method: A systematic literature search and standardized data extraction followed the MDSGene protocol, encompassing individuals with PARK-PRKN, PARK-PINK1, and PARK-PARK7 as of November 2025. This update extends the 2018 MDSGene review¹ (which previously reported 1,127 patients) and applies a novel pathogenicity scoring system across all included cases.

Results: A total of 2,178 individuals were included, comprising 1,864 with PARK-PRKN, 235 with PARK-PINK1, and 79 with PARK-PARK7. The median age at onset (AAO) was 31 years for PARK-PRKN (IQR: 23-38; missing data: 11.3%; range: 1-84 years), 32 years for PARK-PINK1 (IQR: 25-40; missing data: 11.1%; range: 9-67 years), and 27 years for PARK-PARK7 (IQR: 22-35; missing data: 19.0%; range: 5-54 years). Subgroup analyses revealed differences in AAO across distinct ethnicities and sexes, with a tendency toward later AAO in females. Since the first systematic MDSGene review in 2018, geographic diversity has expanded markedly (PARK-PRKN: 54 vs. 36 countries; PARK-PINK1: 38 vs. 28; and PARK-PARK7: 16 vs. 7 countries). Clinical signs and symptoms exhibit substantial missing data, especially for non-motor symptoms (up to 96%).

Conclusion: This largest-to-date dataset refines the clinical and genetic spectrum of autosomal recessive PD, enabling subgroup analyses and highlighting improved representation of previously underrepresented populations. The broad AAO range points to considerable modifying factors in autosomal recessive PD. Gaps in clinical data underscore the need for systematic, standardized phenotypic reporting in monogenic PD, which can be addressed by prospective studies with harmonized phenotyping to improve clinical characterization and thus support the development of precision medicine approaches.

References: 1Kasten M, Hartmann C, Hampf J, Schaake S, Westenberger A, Vollstedt EJ, Balck A, Domingo A, Vulinovic F, Dulovic M, Zorn I, Madoev H, Zehnle H, Lembeck CM, Schawe L, Reginold J, Huang J, König IR, Bertram L, Marras C, Lohmann K, Lill CM, Klein C. Genotype-Phenotype Relations for the Parkinson’s Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review. Mov Disord. 2018 May;33(5):730-741. doi: 10.1002/mds.27352. Epub 2018 Apr 11. PMID: 29644727.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mdsgene-literature-update-on-autosomal-recessive-parkinsons-disease/