Genetic Testing

 Clinical Best Practices

  • Before any genetic testing occurs, it is wise to refer the patient and his or her family for genetic counseling to consider the reasons for doing the testing and the impact it may have on the patient and his or her family.
  • Genetic findings will have implications for the family and patients should consider the impact.
  • Currently, the therapeutic recommendations for Parkinson's care do not differ based on genetic findings.

 

Genetic testing should not be conducted in every single Parkinson’s patient. However, there are genetic factors that you should consider when dealing with your patient.

Table of Contents 

Considerations

  • The vast majority of PD is sporadic, with only 10% to 15% of patients having a familial form.
  • The three most common mutations are probably in the PARK2 (parkini), LRRK2, and glucocerebrosidase (GBA) genes.  
  • Parkin testing is worthwhile in
    • juvenile onset (before the age of 20)
    • some cases of younger-onset autosomal recessive parkinsonism  
  • GBA mutations are most common in general population.
  • LRRK2 testing may be worthwhile in North African Arabs (30%-40% have LLRK2 gene with 30%-40% penetrance).
  • Genetic testing is predominantly for research purposes and it may help sort out those rare families with an autosomal dominant or recessive form of parkinsonism.
  • There are some small differences in the pathophysiology of PD in some uncommon genetic variants, but these do not currently influence treatment recommendations.
  • Since many mutations may not cause disease or have low rates of expression/penetrance, genetic testing should be left up to the neurologist and more often to an academic medical center with movement disorder specialists who have expertise in genetic forms of parkinsonism.
  • Currently there are commercial companies offering PD genetic testing in the US.  For example, 23andMe offers discounted or free genetic screening to people with Parkinson's disease.  Most patients will benefit from access to a genetic counselor both before and after genetic testing, which 23andMe does not offer.
References: 

Bekris LM, Mata IF, Zabetian CP. The genetics of Parkinson disease. J Geriatr Psychiatry Neurol. 2010;23(4):228-242.

Benamer HT, de Silva R. LRRK2 G2019S in the North African population: a review. Eur Neurol. 2010;63(6):321-325.

Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009;361(17):1651-1661.