Parkinson disease

Parkinson disease belongs to a group of conditions called movement disorders. The four main symptoms are tremor, or trembling in hands, arms, legs, jaw, or head; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance. These symptoms usually begin gradually and worsen with time.  As they become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks.  Not everyone with one or more of these symptoms has Parkinson disease, as the symptoms sometimes appear in other diseases as well.^[1] Parkinson disease affects about 1 to 2 percent of people over the age of 60 years and the chance of developing Parkinson disease increases as we age.^[2] Although some Parkinson disease cases appear to be hereditary most cases are sporadic and occur in people with no apparent history of the disorder in their family. When three or more people are affected in a family, especially if they are diagnosed at an early age (under 50 years)  there may be a gene making this family more likely to develop the condition. Currently, seven genes that cause some form of Parkinson's disease have been identified. Mutations (changes) in three known genes called SNCA (PARK1),UCHL1 (PARK 5), and LRRK2 (PARK8) and another mapped gene (PARK3) have been reported in families with dominant inheritance. Mutations in three known genes, PARK2 (PARK2), PARK7 (PARK7), and PINK1 (PARK6) have been found in affected individuals who had siblings with the condition but whose parents did not have Parkinson's disease (recessive inheritance). There is some research to suggest that these genes are also involved in early-onset Parkinson's disease (diagnosed before the age of 30) or in dominantly inherited Parkinson's disease but it is too early yet to be certain. However, in most cases inheriting a mutation will not cause someone to develop Parkinson's disease because there may be additional genes and environmental factors determining who will get the condition, when they get it and how it affects them.^[1] 

Parkinson disease occurs when the nerve cells in the brain that make dopamine, a chemical messenger which transmits signals within the brain to produce smooth physical movements, are slowly destroyed. Without dopamine, the nerve cells in the part of the brain known as the substantia nigra cannot properly send messages. This leads to progressive loss of muscle function. Exactly why these brain cells waste away is unknown.^[1][3] Recent studies have shown that people with Parkinson disease also experience damage to the nerve endings that produce the neurotransmitter norepinephrine. Norepinephrine, which is closely related to dopamine, is the main chemical messenger of the sympathetic nervous system, the part of the nervous system that controls the automatic functions of the body, including pulse and blood pressure. The loss of norepinephrine may explain some of the non-motor features seen in Parkinson disease, including fatigue and problems with blood pressure regulation.^[1] 

More detailed information about the cause of Parkinson disease is available through an information page developed by the National Institute of Neurological Disorders and Stroke (NINDS). Click here to view this information.

Most cases of Parkinson disease are classified as sporadic and occur in people with no apparent history of the disorder in their family. Although the cause of these cases remains unclear, sporadic cases probably result from a complex interaction of environmental and genetic factors. Additionally, certain drugs may cause Parkinson-like symptoms.^[4]

Approximately 15 percent of people with Parkinson disease have a family history of the disorder. These familial cases are caused by mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene, or by alterations in genes that have not yet been identified. Mutations in some of these genes may also play a role in cases that appear to be sporadic.^[4]

It is not fully understood how mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene cause Parkinson disease. Some mutations appear to disturb the cell machinery that breaks down (degrades) unwanted proteins. As a result, un-degraded proteins accumulate, leading to the impairment or death of dopamine-producing neurons. Other mutations may involve mitochondria, the energy-producing structures within cells. As a byproduct of energy production, mitochondria make unstable molecules, called free radicals, that can damage the cell. Normally, the cell neutralizes free radicals, but some gene mutations may disrupt this neutralization process. As a result, free radicals may accumulate and impair or kill dopamine-producing neurons.^[4]

In some families, alterations in the GBA, SNCAIP, or UCHL1 gene appear to modify the risk of developing Parkinson disease. Researchers have identified some genetic changes that may reduce the risk of developing the disease, while other gene alterations seem to increase the risk.^[4]

Most cases of Parkinson disease occur in people with no family history of the disorder. The inheritance pattern in these cases is unknown. Among familial cases of Parkinson disease, the inheritance pattern differs depending on the gene that is altered. If the LRRK2 or SNCA gene is involved, the disorder is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Parkinson disease is inherited in an autosomal recessive pattern if the PARK2, PARK7, or PINK1 gene is involved. This type of inheritance means that two copies of the gene in each cell are altered. Most often, the parents of an individual with autosomal recessive Parkinson disease each carry one copy of the altered gene but do not show signs and symptoms of the disorder.^[4]

There are currently no blood or laboratory tests that have been proven to help diagnose sporadic cases of Parkinson disease. The diagnosis is generally made after careful evaluation of medical history, current symptoms, and exclusion of other conditions.^[1] The clinical findings of tremor, rigidity, and bradykinesia are highly suggestive of Parkinson disease. The genetic cause of some forms of Parkinson disease has been identified. In those cases, genetic testing may be utilized to identify affected family members.^[5]

GeneTests lists laboratories offering clinical genetic testing for the HTRA2-related, LRRK2-related, PARK7-related, PINK1-related, Parkin, and SCNA-related types of Parkinson disease. Clinical genetic tests are ordered to help diagnose a person or family and to aid in decisions regarding medical care or reproductive issues. Individuals and families who are interested in having genetic testing can learn more about their risk for Parkinson disease and the availability and accuracy of genetic testing for this disease by setting up an appointment with a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.