Clinical and genetic characteristics of patients with early-onset or familial parkinsonism: A retrospective single-center cohort
Jiannan Chen, Qi Hu, Shanshan Wei, Dongxuan Zhang, Zhe ZhaoBackground
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.