Genetics Testing in Parkinson's Disease

Genes are carried in our DNA, units of inheritance that determine the traits that are passed down from parent to offspring. We inherit about 3 billion pairs of genes from our mothers and fathers. They determine the color of our eyes, how tall we may be and also in some instances, the risk we have in developing certain diseases in our lifetime.

As a physician I know the role that genetics plays in determining our health. The degree of influence that our genes have varies of course depending on the disease but both environmental factors and genetics contribute to the development of illness to some extent.

In Parkinson’s, the vast majority of cases are what we call sporadic with no identifiable cause. These non-familial cases mean no other family members have Parkinson’s. However approximately 14% of people affected with PD have a first degree relative (parent, sibling or child) that is also living with the disease. In these familial Parkinson’s cases, the mutated genes that are causing this disease can be inherited in either a dominant pattern or recessive one.

Many affected relatives throughout different generations are usually found in families that have a dominant Parkinson’s gene. An example of this type of inheritance is the genetic mutation SNCA which results in the production of a protein called alpha synuclein which makes up Lewy bodies that are found in the brains of individuals with Parkinson’s. Other mutations LRRK2, VPS35 and EIF4G1 are also inherited dominantly.

In contrast, recessive mutations that act as a risk factor for the development of Parkinson’s disease are represented by cases within one generation as in siblings. The genetic mutations PARKIN, PINK1 and DJ1 genes are examples of this type of inheritance.

These are some of the mutations that are known but there are more that are being discovered on an ongoing basis. Keep in mind however that most genetic forms have low rates of expression or penetrance which basically means that just because you have the gene does not mean you will get Parkinson’s. Even in the case of LRRK2 mutations which are dominant in nature, presence of the gene does not equal development of the disease.

So the question is, when should genetic testing be done? Well your physician may suggest it if your Parkinson’s diagnosis comes at a young age (< 40 years old), if multiple relatives in your family history have also been diagnosed with the same or if you are at high risk for familial Parkinson’s based on your ethnicity (those with Ashkenazi Jewish or North-African backgrounds).

However what is the benefit to having the testing done at the present time? The information may be important for family planning for some individuals although as I said even if the gene is passed on it does not necessarily equal development of disease. (Although that risk is higher in dominant genetic mutations versus recessive ones, on average if a person has a first degree relative with Parkinson’s (ie. a parent or a sibling), their risk of developing the disease is 4 – 9% more than the general population.)

Keep in mind that currently for the person being tested, there is no change in the treatment of their Parkinson’s disease based on genetic findings. In the future however, when there are treatments to slow down the onset of the disease or to prevent it from developing at all, then identification of those people at risk, will be very important.

Although there may be no direct benefit to you at the present time, the results of genetic testing can help further Parkinson’s research by allowing scientists to better understand the disease and consequently develop new treatments. For example a mutation in the gene that codes for the protein alpha synuclein (SNCA) leads to a specific type of familial Parkinson’s disease. Although this mutation only accounts for a small percentage of PD cases, knowledge of this mutation has had broader effects. Study of this genetic mutation led to the discovery that alpha synuclein clumps together to form Lewy bodies which have been consistently found in the brains of all individuals with Parkinson’s disease not just those with the SNCA mutation. Thus one gene mutation has led to a critical finding in the field of Parkinson’s research.

Genetics testing is a very personal decision but a cautionary note: anytime that genetic testing is considered, particularly in a disease condition where there is no change in treatment based on genetic findings, it would be my recommendation to see a genetics counselor to discuss the impact this information will have on you the patient, and your family.