Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, and slowed movement (bradykinesia). Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. Generally, individuals with onset before age 20 years are considered to have juvenile-onset Parkinson disease, those with onset before age 50 years are classified as having early-onset Parkinson disease, and those with onset after age 50 years are considered to have late-onset Parkinson disease.
The diagnosis of Parkinson disease is based solely on the clinical findings of tremor, rigidity, and bradykinesia. A good response to levodopa and asymmetric onset of limb involvement are generally regarded as supporting diagnostic features. The cardinal pathologic feature of Parkinson disease is the loss of dopaminergic neurons in the substantia nigra with intracytoplasmic inclusions (Lewy bodies) in the remaining, intact nigral neurons. The genetic cause of some forms of Parkinson disease has been identified. Seven disease genes have been implicated. Mutations in three known genes, SNCA (PARK1), UCHL1 (PARK5), and LRRK2 (PARK8) and one mapped gene (PARK3) result in autosomal dominant Parkinson disease. Mutations in three known genes, PARK2 (PARK2), PARK7 (PARK7), and PINK1 (PARK6), result in autosomal recessive Parkinson disease. Three susceptibility genes have been identified. Molecular genetic testing is clinically available for PARK2 (the gene encoding parkin), PINK1, PARK7, SNCA, and LRRK2.
Parkinson disease can be inherited in an autosomal dominant or autosomal recessive manner; however, most cases of Parkinson disease are thought to result from the effects of multiple genes as well as environmental risk factors. Genetic counseling of affected individuals and their family members must be done on a family-by-family basis. The risk to first-degree relatives of a person with Parkinson disease varies from study to study and from country to country. In families with a non-mendelian form of Parkinson disease, first-degree relatives of an affected individual are between 2.7 and 3.5 times more likely to develop Parkinson disease than individuals without a family history of Parkinson disease. Their cumulative lifetime risk of developing Parkinson disease is therefore between 3% and 7%.