Parkinson disease

Parkinson disease (PD) is a neurologic disease that affects the movement. The four main symptoms are tremors of the hands, arms, legs, jaw, or head, specially at rest; rigidity, or stiffness; bradykinesia, or slow movement; and postural instability or inability to find balance. The symptoms start slowly, but progress over time, impairing  everyday activities such as walking, talking, or completing simple tasks. Other symptoms may include emotional problems, trouble swallowing and speaking; urinary problems or constipation; skin problems; sleep problems, low blood pressure when standing up from sitting or lying down (postural hypotension), and inexpressive face. Some people will loose their mental abilities (dementia).^[1][2][3]  

Parkinson disease affects several regions of the brain, especially a region known as "substantia nigra" that helps controlling balance and movement. Most cases of PD are sporadic (with no family history), and with onset around 60 years of age; onset before age 20 years is considered to be juvenile-onset Parkinson disease, and after age 50 years is considered late-onset Parkinson disease. However, in some families, there are several cases of Parkinson disease. Familial cases of Parkinson disease, and maybe some sporadic cases, can be caused by changes (mutations) in several genes, such as:^[1][2][4] 

• Mutations in the SNCA (PARK1), LRRK2 (PARK8), and VPS35 (PARK17) genes are inherited in an autosomal dominant manner.
• Mutations in genes PARK2, PARK7, and PINK1 (PARK6) appear to be inherited in a recessive manner.
• Very rare mutations in the TAF1 gene cause Parkinson disease with X-linked inheritance.
• Mutations in some genes, including GBA and UCHL1 (PARK 5), do not seem to cause Parkinson disease, but to increase the risk of developing the disease in some families.

Autosomal recessive PD have earlier onset than autosomal dominant PD. Some studies suggest that these genes are also involved in early-onset or juvenile PD. However, inheriting a mutation does not always mean that a person will have Parkinson's disease, because there may be other genes and environmental factors determining who will develop Parkinson disease.^[2]

Treatment is usually based on a medication known as levodopa. Other medication includes bromocriptine, pramipexole, ropinirole, amantadine, rasagiline and safinamide.  Deep brain stimulation (DBS) a surgical procedure where electrodes are implanted into the brain may be useful for some people.^[3][2] Prognosis varies, and while some people become disabled, others will have only minor movement problems.^[2] Studies have shown that people with PD who have cognitive impairment, postural hypotension, and sleep problems may have a more rapid progression of the disease.^[5]

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.^[2][6] 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.^[2] 

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.^[7]

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.^[7]

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.^[7]

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.^[7]

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.^[7]

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.^[2] 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.^[4]

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 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.