Objective: To describe a rare likely pathogenic variant of the PLA2G6 protein and its response to deep brain stimulation (DBS).

Background: PLA2G6-associated neurodegeneration (PLAN) can be classified into four subtypes based on the age of onset [1]. Adult-onset dystonia-parkinsonism is a subtype characterized by a slow progression in the 3^rd-4^th decades of life, a substantial reduction in dopamine transporter activity, and response to dopaminergic agents. This is the second c.609G>A variant reported to date [2], and the first one to our knowledge to undergo DBS implantation.

Method: Case report.

Results: A 37-year-old woman with consanguineous parents presented for evaluation of progressive gait difficulty and bilateral lower extremity pain that had been present for two years. She reported abnormal curling of her toes and stiffness in her legs. Initial evaluation included a brain MRI that showed cerebral and cerebellar atrophy. EMG/NCS was normal. Given her dystonic and parkinsonism features, she was started on carbidopa/levodopa with moderate improvement in her symptoms but significant nausea and wearing off. Genetic testing for dystonia was done and showed a homozygous VUS in PLA2G6, exon 4, c.609G>A (silent), with RNA analysis indicating an altered splicing pattern that could result in the loss of 3 amino acid residues. A DaTscan showed decreased bilateral uptake in the striatum [figure 1]. Bilateral GPi DBS was implanted with good response at 3.0mA/100PW/65Hz (L) and 3.2mA/100PW/65Hz (R), although with persistent balance difficulties.

Conclusion: PLAN is a syndrome that can be responsive to neurostimulation. PLA2G6 dysfunction can cause altered Golgi morphology, O-linked glycosylation, and sialylation defects, which can induce Lewy body and tau pathology [2]. Reporting novel variants provides further understanding of this condition and expands the knowledge about therapeutic strategies that can benefit patients.

Figure 1

References: 1. Guo YP, Tang BS, Guo JF. PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes. Front Neurol. 2018 Dec 18;9:1100. doi: 10.3389/fneur.2018.01100. PMID: 30619057; PMCID: PMC6305538.
2. Davids M, Kane MS, He M, Wolfe LA, Li X, Raihan MA, Chao KR, Bone WP, Boerkoel CF, Gahl WA, Toro C. Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration. J Med Genet. 2016 Mar;53(3):180-9. doi: 10.1136/jmedgenet-2015-103338. Epub 2015 Dec 14. PMID: 26668131; PMCID: PMC5535303.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-a-patient-with-dystonia-parkinsonism-secondary-to-a-c-609ga-pla2g6-associated-neurodegeneration-variant/