PRKN-Gene-Related Parkinsonism: An Experience from a Tertiary Centre and Literature Review of Asian Cohort.

BACKGROUND

PRKN-related parkinsonism represents one of the most common types of genetically determined Parkinson's disease (PD). However, the literature among the Asian ethnicity, particularly in the Indian context, is limited.

OBJECTIVE

To study the clinico-genetic profile of patients with PRKN-related parkinsonism and to review the previously reported cases of PRKN-related parkinsonism from Asia.

METHODS

A retrospective chart review from a tertiary neurology centre of patients with genetically confirmed PRKN-related parkinsonism. Additionally, we consolidated the Asian cohort from a detailed systematic review of the literature. We utilised the Movement Disorders Society gene cohort for comparison with the world literature.

RESULTS

We recruited 16 cases (males = 10, Early onset Parkinson disease (21 to <50 years age at onset)) of PRKN-related parkinsonism with a median age at onset of 28.5 years (range 14-46). Symptoms included parkinsonism (n = 15), dystonia (n = 10), postural instability (n = 7), freezing of gait (n = 5) and non-motor symptoms (NMS) (n = 10). The commonest symptom at onset was tremors (n = 10). Levodopa responsiveness was observed in all cases with drug-induced dyskinesia in eight (50%). Thirteen cases were homozygous, while three were compound heterozygotes, resulting in 19 variants (novel = 5). Exon deletion was the most common (n = 12). The extended Asian cohort comprising 294 cases had a high prevalence of EOPD (n = 186/257, 72.4%) and familial cases (n = 166/252, 65.9%). Deletion/duplication was the common mutation detected (n = 215, 73.1%). The presumed familial cases had a significantly higher frequency of rest tremors, bradykinesia, postural instability, NMS, dyskinesia and sleep disorders.

CONCLUSION

This largest single-centre study from India adds 16 new cases and five novel variants to PRKN literature. In addition, it consolidates the Asian cohort of PRKN elucidating its unique attributes.