Objective: To report a rare presentation of a rare disease and illustrate the range of phenotype seen in PLA2G6-associated dystonia-parkinsonism (PLADP).

Background: PLA2G6 encodes a calcium-independent phospholipase which plays a role in cell membrane homeostasis. Its mutation leads to membrane dysfunction and the brain iron accumulation occurring in some PLA2G6-associated disease. PLADP manifests in the second decade of life with parkinsonism, dystonia, cerebellar, pyramidal and neuropsychiatric signs. The average age of onset is 26 (+/- 8.6) years. MRI abnormalities, present in 74.3%, include cerebral (51.4%) and cerebellar atrophy (14.3%), and pallidal iron deposition (8.6%).

Method: To describe a case of late onset PLADP and report two novel variants in the PLA2G6 gene.

Results: A 79-year-old woman presents with a 20 year history of depression and hand tremor and a 9 year history of cervical dystonia. She reports 3 years of gait impairment now requiring the use of a walker. Her identical twin sister, seen outside our institution, reported 20 years of kinetic tremor and 3 years of gait impairment, cognitive dysfunction, and depression. Examination shows a yes-yes head tremor, right torticollis, and left laterocollis. There is moderate kinetic tremor of both hands, mild right hand rest tremor, rigidity and bradykinesia. Her gait is wide-based, shuffling with en bloc turns. MRI Brain shows a severe burden of confluent subcortical T2 FLAIR hyperintensities and global cerebral atrophy with no iron deposition. Genetic testing of the patient and her twin reveals two heterozygous variants of unknown significance in the PLA2G6 gene: c.1649 G>A p.(R550Q) in exon 12 and c.995 G>C p.(C332S) in exon 7, not yet published in association with PLADP. The patient’s tremor and gait responded significantly to levodopa and she no longer requires the use of a walker to ambulate.

Conclusion: We present a case of PLADP, onset at age 59, representing a significant deviation from the reported age of onset. The patient and her twin have novel heterozygous mutations, expanding upon the existing phenotype-genotype literature. Her extensive T2 FLAIR hyperintensities are unusual in this clinical setting and further evaluation is needed to determine if they are related.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pla2g6-related-dystonia-parkinsonism-in-identical-twins-manifesting-at-an-advanced-age-a-case-report-and-review-of-the-literature/