Category: Parkinsonism, Atypical: MSA
Objective: To characterize a North-Bavarian (Lion’s tail region) six-generation pedigree, including neuropathologically confirmed multiple system atrophy and Parkinson’s disease with dementia.
Background: Multiple system atrophy is considered a sporadic disease, but neuropathologically confirmed cases with a family history of parkinsonism have been occasionally described.
Method: Between 2012 and 2020, we examined all living and consenting family members of age and calculated the risk of prodromal Parkinson’s disease in those without overt parkinsonism. The index case and one paternal cousin with Parkinson’s disease with dementia died at follow-up and underwent neuropathological examination. Genetic analysis was performed in both and another family member with Parkinson’s disease.
Results: The index case was a female patient with cerebellar variant multiple system atrophy and a positive maternal and paternal family history for Parkinson’s disease and dementia in multiple generations. The families of the index case and her spouse were genealogically related, and one of the spouse`s siblings met the criteria for possible prodromal Parkinson’s disease. Neuropathological examination confirmed multiple system atrophy in the index case and advanced Lewy body disease, as well as tau pathology in her cousin. A comprehensive analysis of genes known to cause hereditary forms of parkinsonism or multiple system atrophy lookalikes was unremarkable in the index case and the other two affected family members.
Conclusion: Here we report an extensive European pedigree with multiple system atrophy and Parkinson`s disease indicating a complex underlying α-synucleinopathy as confirmed on neuropathological examination. The exclusion of known genetic causes of parkinsonism or multiple system atrophy lookalikes suggests that variants in additional, still unknownn genes, linked to α- synucleinopathy lesions may have caused such neurodegenerative clustering.
To cite this abstract in AMA style:
A. Fanciulli, F. Leys, F. Lehner, V. Sidoroff, V. Ruf, C. Raccagni, P. Mahlknecht, D. Kuipers, W. van Ijcken, H. Stockner, T. Musacchio, J. Volkmann, C. Monoranu, I. Stankovic, G. Breedveld, F. Ferraro, C. Fevga, O. Windl, J. Herms, S. Kiechl, W. Poewe, K. Seppi, N. Stefanova, S. Scholz, V. Bonifati, G. Wenning. The Lion’s tail family: A Bavarian multiplex pedigree with pathologically confirmed multiple system atrophy and Parkinson’s disease with dementia [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/the-lions-tail-family-a-bavarian-multiplex-pedigree-with-pathologically-confirmed-multiple-system-atrophy-and-parkinsons-disease-with-dementia/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-lions-tail-family-a-bavarian-multiplex-pedigree-with-pathologically-confirmed-multiple-system-atrophy-and-parkinsons-disease-with-dementia/