PLA2G6-associated neurodegeneration in four different populations-case series and literature review

Background PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases. Methods Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review. Results Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3. Conclusions PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics.