22q11.2 deletion syndrome raises risk of early Parkinson’s by 6 times
Motor symptom onset often before age 50 in people with genetic condition
The prevalence of early-onset Parkinson’s disease is six times higher among adults with a genetic condition called 22q11.2 deletion syndrome compared with the general population, an international study reported.
Previously known as DiGeorge syndrome, 22q11.2 deletion syndrome is caused by a deletion of a small piece of chromosome 22 at a location called 22q11.2. Symptoms can vary, and they may include developmental and intellectual disabilities, heart defects, unique facial characteristics, kidney problems, and a cleft palate.
For 22q11.2DS patients older than age 50, Parkinson’s prevalence was greater than that of the overall group, the research showed.
“Given high [Parkinson’s] prevalence and young onset, we propose periodic motor evaluations from age 40 years in 22q11.2 [deletion syndrome],” the scientists wrote.
Link between 22q11.2 deletions, early Parkinson’s detailed about decade ago
The study, “Prevalence of Parkinson’s Disease in 22q11.2 Deletion Syndrome: A Multicenter Study,” was published in Movement Disorders.
A study published in 2013 was the first to report that 22q11.2 deletions represented a novel genetic risk factor for early-onset Parkinson’s disease. Then, a 2018-published study pointed to similarities in major clinical characteristics and standard treatment responses between people with 22q11.2-associated Parkinson’s and those with idiopathic Parkinson’s (of unknown cause).
Because most of the 159 participants in the 2013 study were younger than age 35, an international team led by scientists at Maastricht University, in the Netherlands, investigated the prevalence of Parkinson’s in a large group of people with 22q11.2.
Researchers reviewed the medical records of 856 individuals, ages 16-76 (median age 28), with a typical 22q11.2 deletion and being treated at specialty clinics in Belgium, Canada, Chile, and the Netherlands. A little more than half of this group were female (53%).
Parkinson’s was defined as a clinical diagnosis given by a neurologist, with disease symptoms that included bradykinesia (slowed movements) and at least either resting tremor or rigidity, after ruling out other causes of parkinsonism.
Across 22q11.2 patients of all ages, the prevalence of Parkinson’s was 1.8%, which is six times higher than the general population at 0.3%, the scientists noted.
For those 50 years and older, Parkinson’s prevalence rose to 14%, which was “markedly higher than those in the general population several decades older, where [Parkinson’s] is seen in approximately 3.0%,” they wrote.
Parkinson’s prevalence similar among males, females with 22q11.2 deletions
Among those who developed Parkinson’s, the median age at the onset of motor symptoms was 45, ranging from 20 to 66. About 1 in 4 (26.7%) showed motor symptoms before the age of 40, and nearly all (80.0%) before the age of 50, meeting the criteria for early-onset Parkinson’s.
In the general population, men are more likely to develop Parkinson’s than are women, but the disease’s prevalence was similar among 22q11.2 males and females at any age. This suggests that “factors other than sex may impact [Parkinson’s] risk in 22q11.2 [deletion syndrome],” the scientists wrote.
A group of 22q11.2 patients was considered as having uncertain Parkinson’s — defined as a clinical disease diagnosis or suspicion, but without the motor symptoms establishing Parkinson’s for this study. For example, this group may include cases where a definite Parkinson’s diagnosis was deferred due to the use of antipsychotic medications, which are “know to cause parkinsonism,” the researchers wrote.
But when these patients were included in analyses, the prevalence of Parkinson’s rose to 3.4% overall and 23.7% among those 50 years and older. Again, the findings were similar for 22q11.2 patients of either sex of any age.
Statistical analyses failed to identify factors that may predict Parkinson’s risk in these patients, like sex, the presence of intellectual disability, or a history of antipsychotic medications, the team noted.
“This study quantifies the increased risk of developing [Parkinson’s] in adults with 22q11.2 [deletion syndrome] compared to individuals from the general population,” the researchers wrote. “Based on the findings in this study, we propose periodic systematic motor examinations from the age of 40 years, in order to enable early diagnosis and treatment.”
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