Parkinson's disease and genetics
Parkinson's disease (PD) is a progressive neurological disorder characterized by symptoms such as tremors, muscle stiffness, and difficulty with movement and coordination. The disease primarily affects individuals aged fifty and older, although not exclusively, and men are slightly more likely to develop PD than women. Genetics plays a significant role in the onset of Parkinson's, with approximately 15% of cases linked to specific gene mutations, including PARK2, PARK7, PINK1, LRRK2, and SNCA. Mutations in these genes can lead to the gradual degeneration of nerve cells in the brain, contributing to the symptoms associated with PD.
Most genetic cases of Parkinson's are inherited in either an autosomal recessive or dominant manner, influencing the likelihood of transmission to offspring. In addition to genetic factors, environmental influences and exposure to certain toxins may also increase the risk of developing the disease. Currently, there are no cures for PD, and treatments focus on symptom management, including medications and potential surgical interventions. Research continues into the genetic aspects of Parkinson's, aiming to better understand its complexities and develop more effective treatments. Through this exploration of genetics and environmental factors, individuals can gain insights into their own health and the broader implications of Parkinson's disease.
Parkinson's disease and genetics
Also known as: Parkinson’s disease; PD; paralysis agitans; shaking palsy
Definition Parkinson's disease (PD) is a progressive movement disorder that causes muscle rigidity, tremor at rest, slowing down of movements (bradykinesia), difficulty moving, and gait instability. The disorder is caused by a loss of nerve cells in the brain, including loss in an area called the substantia nigra. This loss decreases the amount of dopamine in the brain. Low dopamine results in PD symptoms.
Risk Factors
Individuals at increased risk for Parkinson's disease include those who are fifty years old or older, have a history of polio, have family members with PD, and are nonsmokers. Men are slightly more likely than women to develop PD. Other risk factors are exposure to toxins, drugs, or the conditions listed above.
Etiology and Genetics
The causes of Parkinson's disease are complex and poorly understood, but it is clear that both genetic and environmental factors are involved. In about 85 percent of new cases, the disease appears in people with no family history of the disorder. In the remaining 15 percent of cases, mutations in any one of five different genes (PARK2, PARK7, PINK1, LRRK2, and SNCA) might be responsible. Scientists have been able to pinpoint more than twenty-four genetic risk factors for Parkinson's.
The PARK2 gene, found on chromosome 6 at position 6q25.2-q27, is a very large gene that specifies the protein called parkin. This protein is an important component of a cellular system designed to rid the cell of damaged or excess proteins. Loss of parkin function because of a mutation in the gene could result in an accumulation of defective proteins in the nerve cells of the brain that can lead to cell death and the characteristic symptoms of Parkinson's disease. The PARK7 gene on chromosome 1 (at position 1p36.33-p36.12) encodes a protein called DJ-1, which has several functions, one of which is similar to parkin. The PINK1 gene, also found at location 1p36, encodes the protein PTEN induced putative kinase 1. This protein is important for proper mitochondrial function, but it is unclear why the lack of this protein as a result of a mutation in the PINK1 gene causes the death of nerve cells that lead to Parkinson's disease.
Parkinson's disease that results from mutations in any of these three genes is inherited in an autosomal recessive manner, which means that both copies of the gene must be deficient in order for the individual to be afflicted. Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected.
The LRRK2 gene (at position 12q12) specifies a protein called dardarin, which is a complex protein with at least three different enzyme activities. It is unclear why loss of this protein causes Parkinson's disease symptoms to occur. Finally, the SNCA gene (at position 4q21) encodes the protein alpha-synuclein, which is abundant in the presynaptic vesicles in brain neurons. Most mutations in this gene that cause Parkinson's disease result in an excess production of alpha-synuclein, although it is unclear how this excess impairs proper nerve cell function.
Parkinson's disease that results from mutations in either of these two genes is inherited in an autosomal dominant fashion, meaning that a single copy of the mutation is sufficient to cause full expression of the disease. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children.
Symptoms
Symptoms of PD begin mildly, and they will worsen over time. Symptoms include a “pill-rolling” tremor in the hands. Tremors are present at rest, improve with movement, and are absent during sleep.
Other symptoms include stiffness and rigidity of muscles, usually beginning on one side of the body; difficulty and shuffling when walking; short steps; slowness of purposeful movements; trouble performing usual tasks due to shaking in the hands; trouble speaking; a flat, monotonous voice; stuttering; a shaky, spidery handwriting; poor balance; difficulty rising from a sitting position; and “freezing.” Anxiety; seborrhea (a skin problem that causes a red rash and white scales); a tendency to fall; stooped posture; an increasingly masklike face, with little variation in expression; trouble chewing and swallowing; depression; dementia; difficulty thinking; problems with memory; loss of or decreased sense of smell; and sleep problems, such as rapid eye movement (REM) behavior disorder, are also symptoms.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history and a physical exam will be done. There are no tests to definitively diagnose PD. The doctor will ask many questions, which will help to rule out other causes of a patient’s symptoms.
Tests to rule out other conditions may include blood tests; urine tests; a computed tomography (CT) scan, a type of x-ray that uses a computer to make pictures of structures inside the head; a magnetic resonance imaging (MRI) scan, a test that uses magnetic waves to make pictures of structures inside the head; and a positron emission tomography (PET) scan, a test that makes images that show the amount of activity in the brain.
Treatment and Therapy
Currently, there are no treatments to cure PD. There are also no proven treatments to slow or stop its progression.
Some medications are used to improve symptoms. Over time the side effects may become troublesome, and the medications may lose their effectiveness. Medications include levodopa/carbidopa (Sinemet); amantadine (Symmetrel); anticholinergics, such as benztropine (Cogentin) and biperiden (Akineton); selegiline (Eldepryl); and dopamine agonists, such as bromocriptine (Parlodel), pramipexole (Mirapex), cabergoline (Dostinex), and ropinirole (Requip). Cabergoline (Dostinex) has been shown to have side effects, including several serious ones. Additional medications for PD include apomorphine (Apokyn) and COMT (catechol-O-methyltransferase) inhibitors, such as entacapone (Comtan) and tolcapone (Tasmar).
Medicine may also be given to relieve the depression or hallucinations that may also occur with PD. These medications may include selective serotonin reuptake inhibitors (SSRIs) and antipsychotic clozapine. These drugs can worsen other symptoms. Patients who take them will need to be closely followed.
Different brain operations are available, and many more are being researched. Deep brain stimulation (DBS) involves implanting a device to stimulate certain parts of the brain. DBS can decrease tremor and rigidity. Thalamotomy and pallidotomy destroy certain areas of the brain to improve tremor when medication does not work; these operations are not as common as DBS. Research is being conducted about the possible use of nerve-cell transplants to increase the amount of dopamine made in the brain. A Harvard Stem Cell Institute study, released in 2014, found that Parkinson's patients responded positively to the transplantation of fetal dopamine cells.
Physical therapy can improve muscle tone, strength, and balance; it will include exercises and stretches. Patients with PD can also join a support group with other people who have the disorder. Participation in the support group will help patients learn how others are learning to live with the challenges of PD.
Prevention and Outcomes
There are no guidelines for preventing PD.
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