Gene variants impact survival in monogenic Parkinson’s disease

Survival of patients with monogenic forms of Parkinson’s disease (PD) may be affected by specific gene mutations. The records of 2,037 PD patients were analysed from their first hospital visit and results showed that patients with LRRK2 or PRKN gene mutations had a longer survival time while the survival time was shorter for patients with SNCA or GBA gene mutations.

The most common mutations causing PD are in the SNCA, LRRK2, and PRKN genes while variants in glucocerebrosidase (GBA) are considered as risk factors. Monogenic forms of PD account for approximately 5% of all cases, as most appear to occur sporadically, without any family history. A change in the LRRK2 gene is probably the most common genetic variant associated with PD, causing people who carry this variant to have a 70% risk of being diagnosed with PD by the age of 80.

A study presented by Dr Aymeric Lanore (Paris Brain Institute, France) was the first to compare mortality of patients carrying SNCA, LRRK2, PRKN, or GBA variants responsible for monogenic forms of PD [1]. Data was retrieved from a large multicentre cohort of PD patients, 2,037 of whom were included in this analysis. During follow-up, 890 of the 2,037 participants died. Gene mutations in LRRK2 (HR 0.49; 95% CI 0.26–0.90) and PRKN (HR 0.41; 95% CI 0.24–0.70) were associated with a smaller risk of death than PD patients without any known mutation (see Figure). Two other mutations were associated with shorter survival: SNCA (HR 9.88; 95% CI 4.78–20.40) and GBA (HR 1.33; 95% CI 1.00–1.78).

Figure: Survival probability by genetic status: SNCA, LRRK2, PRKN, or GBA [1]

“The results suggest that the shorter survival of SNCA and GBA patients may be related to faster motor progression of the disease and earlier development of cognitive impairment,” explained Dr Lanore. “These are important new insights which could help the development of new drugs targeting these genetic variants to slow down or stop the disease.” She added that these findings may also enable clinicians to have honest conversations with their patients about expected survival times. “This can empower patients to make decisions about their care and what to do with the time they may have left.”

1. Lanore A, et al. Survival in monogenic forms of Parkinson’s disease: results of a large retrospective study. OPR-085, EAN 2022, 25–28 April, Vienna, Austria.

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Posted on 22 August, 2022