Objective: The aim of this case report is to describe and expand LRRK2 phenomenology, including clinical presentation and disease course.

Background: LRRK2 is the most common risk gene for Parkinson’s Disease (PD). Its typical phenomenology is indistinguishable from idiopathic PD, except for a milder course and a less common non-motor involvement.

Method: We describe two sisters, one presenting with cervical dystonia (CD) and the other one presenting with typical parkinsonian features, although showing prominent non-motor fluctuations.

Results: A 80-year old lady was referred to our outpatient clinic due a 2-year history of head tremor. She showed cervical dystonia characterized by head tremor, inclination to the left side, left shoulder elevation, head rotation to the right, antecollis, retrocaput and limitation of range of motion. She had mirror movements and overflow while performing tasks with both upper limbs, dystonic posture and postural tremor of the upper limbs. Her gait was characterized by normal stride length and reduced velocity, with no arm swing on the right-hand side. She had positive family history for Parkinson’s Disease (two of her mother’s siblings, one of her father’s and 5 of her own).  Her sister was a 83-year old lady, who had been diagnosed with Parkinson’s Disease 8 years previously. Her major complaints were related to her non-motor fluctuations: her OFF phases were characterized by severe anxiety, pain and crying crisis. We run genetic testing for both patients and found the CD one to be a heterozygotic carrier of LRRK2 G2019S mutation and the PD sister to be a homozygotic carrier of the same mutation. We added safinamide and duloxetine to the treatment of the PD sister, with a major impact on non-motor fluctuations and QoL, and decided to treat the CD sister with levodopa/carbidopa, with considerable clinical improvement.

Conclusion: Our cases show that LRRK2 G2019S may have variable clinical presentation, including CD, and it can show prominent non-motor fluctuations. Our data may contribute to expanding LRRK2 phenotype and providing insights on its clinical course and treatment.

References: 1. Ito G, Utsonomyia-Tate N, Overview of the impact of pathogenic LRRK2 mutations in Parkinson’s Disease, Biomolecules 2023, 13, 845. https://doi.org/10.3390/biom13050845;
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3. Saunders-Pullman R, Raymond D, Elango S, LRRK2 Parkinson’s Disease, [Updated 2023 Jul 6]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023;
4. Shu L, Zhang Y, Pan H, Xu Q, Guo J, Tang B, Sun Q, Clinical heterogeneity among LRRK2 variants in Parkinson’s Disease: a meta-analysis, Front. Aging Neurosci. 10:283. doi: 10.3389/fnagi.2018.00283;
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MDS Abstracts - https://www.mdsabstracts.org/abstract/expanding-phenotype-of-lrrk2-g2019s-mutation-case-description-of-two-sisters-showing-peculiar-phenomenological-traits/