Genetic syndrome may underlie some Parkinson's cases

By Eleanor McDermid

Rare deletions at chromosome 22q11.2 are present at an increased rate in patients with Parkinson's disease (PD), researchers report in The Lancet Neurology.

PD has been reported in patients with 22q11.2 deletion syndrome, which is a heterogeneous, multisystem disorder, with features including cleft palate, cardiac and skeletal abnormalities and learning difficulties. This latest study shows the converse to be true, with 22q11.2 deletions present in eight of 9387 PD patients from four independent studies, but none of 13,863 controls.

The eight identified patients all had the 3 Mb deletion, the most common form of 22q11.2 deletion. The deletion was associated with an early age at PD onset, at an average of 42.1 years compared with 60.3 years among patients without the deletion.

Even among patients with early-onset (<45 years) PD, the rate of 22q11.2 deletions was just 0.49% (0.04% for later onset). But researcher Nicholas Wood (UCL Institute of Neurology, London, UK) and colleagues stress that "the presence of a 22q11.2 deletion has direct implications for management, especially the identification and medical management of comorbidities."

None of the patients had a diagnosis of 22q11.2 deletion syndrome, but the team says: "With hindsight, some cases had other features suggestive of 22q11.2 deletion syndrome, such as hypocalcaemia, depression, fatigue, mental retardation, and cleft palate."

They did not, however, have any of the cardiac features that are frequently reported in 22q11.2 deletion syndrome patients.

In a linked commentary, Eng-King Tan (Singapore General Hospital) stresses that, although the findings may focus a search for a novel PD gene, they do not prove that the deletion causes PD. For one thing, it is not clear why only 3% of patients with such deletions develop PD and what might trigger the condition in those who do develop it, he says.

"Despite many missing connections in the pathophysiological link between 22q11.2 deletion syndrome and Parkinson's disease, the present study will certainly raise clinicians' awareness and heighten their vigilance in looking for features of 22q11.2 deletion syndrome in patients with early-onset Parkinson's disease, and carefully considering Parkinson's disease as a differential diagnosis in patients with 22q11.2 deletion syndrome even if these patients are on antipsychotic drugs", he concludes.

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