Clinical and Molecular Spectrum of Nonsyndromic Early‐Onset Osteoarthritis

Abstract

Objective Osteoarthritis (OA) is the most common joint disease worldwide. The etiology of OA is varied, ranging from multifactorial, environmental to monogenic. OA can occur earlier in some individuals than in the general population, called early‐onset osteoarthritis (EO‐OA). To our knowledge, we lack large‐scale genetic studies of individuals with EO‐OA. Here we aimed to study monogenic osteoarthritis causes in individuals with non‐syndromic EO‐OA. Methods From 2013 to 2019, skeletal dysplasia experts referred non‐syndromic EO‐OA probands to our skeletal disease center. Criteria for EO‐OA are based on: X‐Ray evidence, BMI ≤ 30, age of onset ≤ 50 and ≥ 1 joint site involved. Molecular analyses involved next‐generation sequencing panel approach. Results We identified a pathogenic variant in 13/45 (29%) probands: 11 COL2A1, 1 ACAN and 1 SLC26A2 . After familial segregation analysis, 20 additional individuals were included. Mean age of onset of joint pain was 19.5 ±3.9 (95% CI) years. Eighteen out of 33 (55%) individuals presenting non‐syndromic EO‐OA and carrying a pathogenic variant had at least one joint prosthesis (mean age: 41 years ±4.2 (95% CI); mean number of prosthesis: 2.6 per individual), and 21 (45%) of the joint replacement surgeries were performed before age 45 years. For the 20 individuals > 40 years old, 17 (85%) had at least one prosthesis. Conclusion We confirmed that COL2A1 is the main monogenic cause of non‐syndromic EO‐OA. However, on the basis of genetic heterogeneity of EO‐OA, we recommend next‐generation sequencing for all individuals with joint replacement before age 45 years. Lifestyle recommendations for prevenion should be implemented.