Adult-onset PLA2G6-associated neurodegeneration (PLAN) has a diverse phenotypic presentation.

Detailed description of the clinical, imaging and genetic profile of adult-onset PLAN; comparison of the Indian cohort with Asian, Middle East and European cohorts; genotype–phenotype correlations; and determination of ethnic phenotypic and genotypic differences of adult-onset PLAN.

Report of two patients of adult-onset PLAN and review of reported cases of adult-onset PLAN since 2015 from Indian, Asian, Middle East and European cohorts.

There were 12 cases in the Indian cohort, 45 in the Asian cohort, 10 in the Middle East cohort and 17 in European cohort. Patients in the Indian and Asian cohorts had a later age at onset as compared to the Middle East and European cohorts. The median duration of disease was similar among all cohorts. Dystonia, myoclonus and gaze palsy were common in the Indian cohort; parkinsonism and tremor in the Asian cohort; parkinsonism, tremor, spasticity and cognitive impairment in the Middle East cohort; and parkinsonism and behavioural disturbances in the European cohort. Early-onset parkinsonism was common in all cohorts. Mineralisation on MRI was less frequent in the Asian and Middle East cohorts. Cerebral/cerebellar atrophy was less frequent in the Asian cohort. The homozygous missense variant (c.2222G > A,p.R741Q) was common in the Indian and Middle East cohorts, whereas the homozygous/compound heterozygous variant (c.991G > T, p.D331Y) was the most common variant in the Asian cohort. Milder clinical and neuroimaging phenotypes were noted with c.991G > T (p.D331Y) variant and a relatively severe phenotype in c.2222G > A,p.R741Q variant.

Adult-onset PLAN has a variable phenotype. We found ethnic phenotypic and imaging differences among the cohorts.