Parkinson's disease is the second most common neurological disorder (after Alzheimer's disease), affecting approximately 1 percent of the population over age 50 and approximately 500,000 Americans. The cause of most cases of Parkinson's is unknown, but investigations of family histories and rates of Parkinson's in identical and fraternal twins have made it clear genetic factors play a role. Rare cases of Parkinson's are inherited in a more strictly genetic manner; some families appear to have autosomal recessive Parkinson's and others have an autosomal dominant form of the condition.
Idiopathic
In most cases of Parkinson's disease, no specific pattern of inheritance is apparent and the condition is called idiopathic. These cases are presumed to result from an interaction of multiple genes and environmental risk factors. Cases of Parkinson's do tend to aggregate in some families, though, suggesting inherited factors play a role. The stronger the family history of Parkinson's, the stronger the influence of genes and the earlier the age of onset. Parkinson's that passes from one generation to the next tends to occur at earlier ages in subsequent generations. Specifically, individuals who have a parent with Parkinson's tend to develop the condition at a younger age (average age 48) than those with an affected sibling (average age 60).
Individuals with even just one close family member with Parkinson's disease have an increased chance of developing the condition. First-degree relatives (siblings, parents, or children) of an individual with Parkinson's are at 2.5 to 3 times higher risk of developing the disease than individuals with no family history of the condition. Having more affected family members further increases an individual's chance of developing the disease.
Autosomal Recessive
In rare families, more than one person in the same generation develops Parkinson's at an unusually early age. This type of history suggests autosomal recessive inheritance. An autosomal recessive condition is one in which a person must inherit two copies of a gene mutation or change, one from each parent, to develop the condition. When both parents are carriers of an autosomal recessive condition, meaning they each carry one copy of a gene mutation, each of their children has a 25 percent chance of inheriting both mutations and developing the condition.
At least two different genes have been implicated in autosomal recessive Parkinson's disease. Hatano and colleagues discovered mutations in one gene, called PARK6, that caused autosomal recessive Parkinson's in some Asian families. In these families, the age of onset ranged from 18 to 56 years, but most people began experiencing symptoms in the third or fourth decade. Bonifati and colleagues identified mutations in another gene, PINK1, in some Italian families with early-onset, autosomal recessive parkinsonism. The age at onset in these families ranged from 28 to 35 years.
Autosomal Dominant
Some rare families have been identified in which Parkinson's occurs at early ages in multiple generations, suggesting autosomal dominant inheritance. The autosomal dominant condition means a person needs only one copy of a gene mutation to develop the condition. Each child of a person with an autosomal dominant condition has a 50 percent chance of inheriting the gene mutation and therefore, the condition. Mutations in several different genes can cause autosomal dominant Parkinson's. Spira and colleagues studied a Greek family in which multiple siblings had Parkinson's disease beginning in their 40s. The researchers found mutations in a gene called SNCA in the affected members of this family.
People with autosomal dominant Parkinson's usually have a parent affected with the condition. However, the family history may appear to be negative because a parent may not have been definitively diagnosed with the disorder or may have died before developing symptoms.
References
- "Neurology;" PARK6-Linked Autosomal Recessive Early-Onset Parkinsonianism . . .; Y. Hatano et al.; 2004
- "Neurology;" Early-Onset Parkinsonism . . ."; V. Bonifati et al.; 2005
- "Annals of Neurology;" Clinical and Pathological Features . . . ; P.J. Spira et al.; 2001
