The phenotypic variation of a PARK-Parkin family and the role of heterozygosity
Journal Paper/Review - Nov 14, 2019
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.
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.
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.