Profiling Non-motor Symptoms in Monogenic Parkinson’s Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elder population, pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While the precise mechanisms underlying the pathogenesis of PD remain unknown, various genetic factors have been proved to be associated with PD. To date, at least 23 loci and 19 disease-causing genes for PD have been identified. Although monogenic (often familial) cases account for less than 5% of all PD patients, exploring the phenotypes of monogenic PD can help us understand the disease pathogenesis and progression. Primary motor symptoms are important for PD diagnosis but only detectable at a relatively late stage. Despite typical motor symptoms, various non-motor symptoms (NMS) including sensory complaints, mental disorders, autonomic dysfunction, and sleep disturbances also have negative impacts on the quality of life in PD patients and pose major challenges for disease management. NMS is common in all stages of the PD course. NMS can occur long before the onset of PD motor symptoms or can present in the middle or late stage of the disease accompanied by motor symptoms. Therefore, the profiling and characterization of NMS in monogenic PD may help the diagnosis and differential diagnosis of PD, which thereby can execute early intervention to delay the disease progression. In this review, we summarize the characteristics, clinical phenotypes, especially the NMS of monogenic PD patients carrying mutations of SNCA, LRRK2, VPS35, Parkin, PINK1, DJ-1, and GBA. The clinical implications of this linkage between NMS and PD-related genes are also discussed.

Non-Motor Symptoms and Associated Factors in Parkinson’s Disease Patients in Addis Ababa, Ethiopia: A Multicenter Cross-Sectional Study

“…The median duration of illness for our patients was four years. This is significantly lower than reports from the western countries ( 19 , 20 ). However, the present results were consistent with previous regional reports ( 13 , 18 , 19 ).…”

“…This is significantly lower than reports from the western countries ( 19 , 20 ). However, the present results were consistent with previous regional reports ( 13 , 18 , 19 ). Such short median duration of illness could be due to relative improvement in health care and access to trained neurologist in recent years in most of African countries including Ethiopia.…”

Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease

“…Most notably, the alterations of clock genes and melatonin levels can be observed in the patients who were in the early stage of PD or recentonset without any PD treatment, and these alterations were not significantly related to the disease severity and duration of PD. Our result suggests that the dysregulation of the peripheral molecular clock could be an early sign for PD, which helps to explain why the circadian-related symptoms, for instance, RBD and autonomic dysfunction, occur in the prodromal phase of PD (Liu and Le, 2020).…”

Genetic Analysis and Literature Review of SNCA Variants in Parkinson's Disease

“…Genetic contributors exert a significant role in the complicated pathogenesis of PD, and considerable progress in establishing its genetic basis has been made since the first disease-causative gene was identified (Hernandez et al, 2016;Deng et al, 2018). Multiple susceptibility genes, diseasecausing genes, and genetic risk loci attributed to PD have been identified (Hernandez et al, 2016;Liu and Le, 2020). Intriguingly, some pleomorphic risk loci overlap with the known causative genes of monogenic PD, such as SNCA, glucosylceramidase beta (GBA), leucine rich repeat kinase 2 (LRRK2), and vacuolar protein sorting 13 homolog C (VPS13C) (Singleton and Hardy, 2011;Nalls et al, 2019;Blauwendraat et al, 2020 (Polymeropoulos et al, 1997;Youn et al, 2019;Chen et al, 2020;Zhao et al, 2020;Brás et al, 2021;Liu et al, 2021).…”

“…PD motor deficits include any or all of the following: bradykinesia/hypokinesia/akinesia, resting tremor, muscular rigidity, postural abnormality, gait disturbance, and freezing. The clinical pictures also include a range of nonmotor manifestations such as olfactory dysfunction, autonomic impairment, cognitive decline, and neuropsychiatric disturbance (Postuma et al, 2015;Liu and Le, 2020).…”