Das Parkinson-syndrom und seine genetischen ursachen - Eine standortbestimmung

Intense research efforts over the past decade have demonstrated the role of genetics in the aetiology of parkinsonism. To date, mutations in six different genes have been identified that can clearly cause the condition and that are inherited in an autosomal dominant or recessive fashion within affected families. Among the recessive forms are mutations in the Parkin, PINK1, DJ-1, and ATP13A2 genes with mutations in the Parkin gene being the most frequent. These forms are usually characterised by an early age of onset (before the age of 40 years). Mutations in the α-Synudein and in the LRRK2 gene are associated with an autosomal dominant pattern of inheritance. Additional causative genes have been localised and the genetic forms have been classified in chronological order of their first description (PARK1-13). There is further evidence for additional mutated genes that have not yet been assigned a "PARK" acronym. The identification of genetic forms of parkinsonism has led to a better understanding of the pathophysiology of the disorder, and frequent variants (polymorphisms) in some of these genes appear to play a role also in the idiopathic form of the disease. Both clinically and pathologically, the genetic forms cannot be distinguished from typical idiopathic Parkinson's disease, and the individual disease course cannot be predicted. At present, a monogenic cause can be identified in about 20% of the patients with an early age of onset and in less than 3% of patients with a late onset of the disorder. Taking into account the considerable amount of time and effort and the high costs involved, genetic testing is recommended only in selected cases and should be accompanied by careful counselling.