Objective: To describe a case of rapidly progressive Pallidopyramidal syndrome related to Parkin gene mutation.

Background: Parkin gene mutations are most commonly found in autosomal recessive early onset Parkinson’s disease cases. 50% of all autosomal recessive and 15% of sporadic patients with early onset PD had an underlying Parkin gene mutation(1). It is characterized by marked levodopa responsiveness, lower limb dystonia and levodopa-induced dyskinesias(2). This disease is very slowly progressive and disease progression more than 50 years have been reported(3).

Method: 27 year male presented with tremulousness in both feet 10 months back and after a few months he noticed bilateral inward and downward deviation of both ankles. He began experiencing insidious onset tremulousness and posturing affecting bilateral wrists. On examination he had brisk reflexes, ill sustained ankle clonus, bilateral plantars extensor, no-no type head tremors, resting and postural tremors in bilateral upper limbs and lower limbs, Dystonic posturing in neck, foot and wrists, bradykinesia and generalized rigidity. His off motor MDS UPDRS part 3 was 109 /132 and after single-dose levodopa challenge test performed with 200mg levodopa was 49. A clinical diagnosis of rapidly progressive pallido pyramidal syndrome was made. His contrast enhanced MRI with SWI sequences were normal. His whole exome sequencing showed PRKN on exon 3-4, chromosome 6:g (162054175_162201130)_(162262766_162443309) deletion, homozygous likely pathogenic variant.

Results: In a case series of 24 patients published by Naheed L Khan et al, just two patients had (8%) had brisk reflexes and the disease duration ranged from 4 to 56 years(4).  Patricio Millar Vernetti et al highlighted extremely atypical phenotypic presentations in 3 patients with compound heterozygous mutations in Parkin gene all 3 cases were having very slowly progressive course and none of these patients had exaggerated reflexes(5).

Conclusion: We have a young male with very rapid advancement of pallidopyramidal syndrome as phenotypic presentation of parkin gene-related juvenile onset parkinsonism syndrome, which was not previously reported in the literature.

References: 1. Stark RS, Walch J, Kägi G. The Phenotypic Variation of a Parkin‐Related Parkinson’s Disease Family and the Role of Heterozygosity. Movement Disorders Clinical Practice. 2019 Nov;6(8):700-3.
2. Morrison KE. Parkin mutations and early onset parkinsonism. Brain. 2003 Jun 1;126(6):1250-1.
3. Brüggemann N, Klein C. Parkin type of early-onset Parkinson disease.
4. Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, Bhatia KP, Quinn N. Parkin disease: a phenotypic study of a large case series. Brain. 2003 Jun 1;126(6):1279-92.
5. Vernetti PM, Rossi M, Merello M. Parkin pleiotropy: extremely atypical phenotypes in patients with compound heterozygous mutations. Tremor and Other Hyperkinetic Movements. 2020;10.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rapidly-progressive-pallidopyramidal-syndrome-related-to-parkin-gene-mutation/