The Phenotypic Variation of a Parkin-Related Parkinson's Disease Family and the Role of Heterozygosity

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disorder with both sporadic occurrence and Mendelian heredity, as it is true for autosomal recessive parkin-related PD (PARK-parkin). Parkin-related PD is characterized by early onset, slow progression, frequent lower limb dystonia, and a robust response to levodopa. Clinicians are increasingly confronted with heterozygous PD patients mimicking dominant inheritance. Nevertheless, the exact clinical implications of heterozygosity are not fully understood. Cases: We present an illustrative PARK-parkin family with 2 affected sisters (compound heterozygous) and their father (heterozygous). One sister expresses the classical phenotype, whereas the other has isolated jerky tremor. The father has left-sided action tremor of the hand with some dystonic posturing without clear bradykinesia and normal DaTSCAN. Conclusion: This case series illustrates the phenotypic variability in parkin-related PD with 1 classical phenotype and 1 patient with isolated jerky tremor. Unilateral hand tremor of the heterozygous father could mislead genetic testing by mimicking dominant inheritance.