Objective: We report a patient with genetic Parkinson disease associated with upper motor neuron dysfunction.

Background: Leucine-rich repeat kinase 2 (LRRK2) mutations have been extensively studied in autosomal dominant forms of Parkinson´s disease (PD) but its pathogenic role in PD remain unresolved. There are LRRK2 PD patients with other atypical symptoms such as dementia or motor neuron dysfunction but several published studies have not found LRRK2 mutations in other neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. However, it is known that LRRK2 gene is involved in lysosomal homeostasis which could be postulated as one of the common pathogenic pathways to this wide clinical spectrum associated with LRRK2 mutation.

Method: We report a 58-year-old woman who began with hypokinetic syndrome in the left hemibody and proximal weakness in right lower limb at the age of 52. In the last 2 years, she has developed motor fluctuations and dyskinesias that required parkinsonian medication adjustment and worsening right leg weakness with hyperreflexia.

Results: Among the tests performed, a transcranial magnetic stimulation test was indicative of an upper motor neuron dysfunction in the right leg and the genetic study showed a heterozygous pathogenic variant p. Gly2019Ser in the LRRK2 gene with variable penetrance. The patient was diagnosed LRRK2 PD associated with upper motor neurone disease. At present, we are contemplating second-line PD treatment options.

Conclusion: LRRK2 mutation is related frequently with PD but it can also be associated with parkinsonism with atypical symtoms such as motor neuron dysfuntion. The disruption in lysosomal homeostasis could be the common pathogenic pathway to this wide clinical spectrum associated with LRRK2 mutations.

References: A. J. Whittle, et al. Pathogenic Lrrk2 substitutions and Amyotrophic lateral sclerosis. J Neural Transm 2007;114:327-329
Carles Gaig, et al. Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration. J Neurol Sci 2008;270:94-8
Susanna Cogo, et al. Leucine-rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease. Journal of Neurochemistry 2020;152:273-283

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinson-disease-with-lrrk2-mutation-associated-with-upper-motor-neuron-dysfunction/