Kantonsspital St.Gallen

The Phenotypic Variation of a Family and the Role of Heterozygosity

Robert S Stark, Julia Walch & Georg Kägi


Parkinson's disease (PD) is a common neurodegenerative disorder with both sporadic occurrence and Mendelian heredity, as it is true for autosomal recessive -related PD (PARK-). 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- 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 -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.
citation Stark R S, Walch J, Kägi G. The Phenotypic Variation of a Family and the Role of Heterozygosity. Mov Disord Clin Pract 2019; 6:700-703.
type journal paper/review (English)
date of publishing 16-09-2019
journal title Mov Disord Clin Pract (6/8)
ISSN electronic 2330-1619
pages 700-703
PubMed 31745481
DOI 10.1002/mdc3.12826