Family History for Neurodegeneration in Multiple System Atrophy: Does it Indicate Susceptibility?

Leys, Fabian; Eschlböck, Sabine; Campese, Nicole; Mahlknecht, Philipp; Peball, Marina; Goebel, Georg; Sidoroff, Victoria; Granata, Roberta; Bonifati, Vincenzo; Zschocke, Johannes; Kiechl, Stefan; Poewe, Werner; Seppi, Klaus; Wenning, Gregor K.; Fanciulli, Alessandra

doi:10.1002/mds.29202

Cited by 4 publications

(1 citation statement)

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“…A positive family history of neurodegeneration in related parkinsonian conditions such as progressive supranuclear palsy and multiple system atrophy, which have overlapping clinical features, pathology, and molecular mechanisms with PD [17][18][19][20][21], is reported in up to 20.4-33.0% [18,[22][23][24] and 40% [25] of cases, respectively, with genetic factors sometimes implicated [17,18,20,26]. In contrast, environmental factors are still very poorly defined in these conditions [20,27,28].…”

Section: Many Patients With Pd Have a Positive Family Historymentioning

confidence: 99%

Parkinson’s Disease is Predominantly a Genetic Disease

Lim,

Klein

2024

Journal of Parkinson’s Disease

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The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson’s disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.5% of PD patients unselected for age at onset and family history. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.

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