Clinical and genetic characteristics of patients with early-onset or familial parkinsonism: A retrospective single-center cohort

BACKGROUND: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease. Hereditary causes account for 10-15% of cases but present considerably more complex clinical manifestations than idiopathic cases. It is therefore imperative to enhance clinicians' recognition of hereditary forms. METHODS: This study enrolled 29 patients with early‑onset or familial parkinsonism. 17 cases were identified with reportable genetic findings using PD-targeted or movement disorders gene panels. Clinical data and genetic data were collected. RESULTS: Among 17 patients, PARK2/PRKN (n = 9) and PARK8/LRRK2 (n = 5) were predominant subtypes, with two cases of PARK14/PLA2G6, and one case of PARK18/EIF4G1. Clinically, bradykinesia affected 17/17 patients, rigidity 15/17, tremor 13/17, and dystonia 7/17 (including one oculogyric crisis). Hyperreflexia occurred in 6/17, cognitive impairment in 2/17, pyramidal signs in 2/17, ataxic dysarthria 1/17, and pes cavus in 1/17. Diurnal fluctuation and sleep benefit occurred exclusively in PARK2/PRKN and PARK14/PLA2G6 patients. Among patients with PRKN, 7/9 exhibited diurnal fluctuations: five had exon rearrangements, one had a splicing mutation, and one had a homozygous variant. Conversely, the two PARK2/PRKN patients without diurnal fluctuations showed no exon deletions/duplications. PARK18/EIF4G1 mutations may manifest incomplete penetrance. CONCLUSION: Among PARK2/PRKN patients in our cohort, a potential association between diurnal fluctuation and exon rearrangements may exist, although this observation requires cautious interpretation. Furthermore, these variants appear to cluster within the N-terminal region of the protein (the start of the RING1 domain and preceding regions). Beyond the common PARK2/PRKN subtype, PARK14/PLA2G6 may also be linked to diurnal fluctuation and sleep benefit.