Parkinson disease

Parkinson disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, including an area called the substantia nigra that controls balance and movement. Parkinson disease may also affect regions of the brain that regulate involuntary functions such as blood pressure and heart activity.

Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms include rigidity or stiffness of the limbs and trunk, slow movement (bradykinesia) or the inability to move (akinesia), and impaired balance and coordination (postural instability).

Many Parkinson disease symptoms occur when nerve cells (neurons) in the substantia nigra die or become impaired. Normally, these cells produce a chemical messenger called dopamine, which transmits signals within the brain to produce smooth physical movements. When these dopamine-producing neurons die or become impaired, communication between the brain and muscles weakens, and eventually, the brain is unable to control muscle movement. In most cases of Parkinson disease, protein deposits called Lewy bodies appear in dead or dying dopamine-producing neurons. (Cases without Lewy bodies are sometimes referred to as parkinsonism instead of Parkinson disease.) It is unclear whether Lewy bodies play a role in killing nerve cells, or if they are part of a protective process.

Generally, Parkinson disease that begins after age 50 years is called late onset disease. It is known as early onset disease if signs and symptoms begin before age 50. Cases that begin before age 20 are sometimes referred to as juvenile onset Parkinson disease.

Parkinson disease affects more than 1 million people in North America and more than 4 million people worldwide. In the United States, Parkinson disease occurs in approximately 13 per 100,000 people and about 50,000 new cases are identified each year. The number of cases is rising with the increasing age of the general population.

Mutations in the LRRK2, PARK2, PARK7, PINK1, and SNCA genes cause Parkinson disease.

The GBA, SNCAIP, and UCHL1 genes are associated with Parkinson disease.

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.

Approximately 15 percent of people with Parkinson disease have a family history of this 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 been identified. Mutations in some of these genes may also play a role in cases that appear to be sporadic.

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, undegraded 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.

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.

Read more about the GBA, LRRK2, PARK2, PARK7, PINK1, SNCA, SNCAIP, and UCHL1 genes.

Most cases of Parkinson disease occur in people with no family history of the disorder. The inheritance pattern, if any, 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.

The inheritance pattern is unclear when an increased risk of Parkinson disease or parkinsonism is associated with mutations in the GBA gene.

SNCAIP and UCHL1 mutations have been identified in just a few individuals. It is unclear whether these mutations are related to Parkinson disease, and the inheritance pattern is unknown.