Phenotypic characterization of patients with early-onset high myopia due to mutations in COL2A1 or COL11A1: Why not Stickler syndrome?

Purpose: Our previous study reported that 5.5% of probands with early-onset high myopia (eoHM) had mutations in COL2A1 or COL11A1. Why were the probands initially considered to have eoHM but not Stickler syndrome (STL)? Methods: Probands and family members with eoHM and mutations in COL2A1 or COL11A1 were followed up and reexamined based on the criteria for STL. Further comprehensive examinations were conducted for patients with eoHM and mutations in COL2A1 or COL11A1 and controls with eoHM without mutations in COL2A1 or COL11A1. We performed comparisons between probands, affected family members with mutations in COL2A1 or COL11A1, and controls with eoHM without mutations in COL2A1 or COL11A1. Results: Twelve probands (8.91 +/- 4.03 years) and 14 affected family members (37.00 +/- 11.18 years) with eoHM and mutations in COL2A1 or COL11A1, as well as 30 controls with eoHM but without mutations in COL2A1 or COL11A1, were recruited. Among them, 25.0% of probands and 50.0% of affected family members met the diagnostic criteria for STL after reexamination. Posterior vitreous detachment/foveal hypoplasia (PVD/FH), hypermobility of the elbow joint (HJ), and vitreous opacity were more frequent in patients with eoHM with mutations in COL2A1 or COL11A1 than in the controls (p = 1.40 x 10(-5), 3.72 x 10(-4), 2.30x 10(-3), respectively). HJ was more common in the probands than in the affected family members (11/12 versus 3/14; p = 3.42 x 10(-4) ), suggesting age-dependent manifestation. EoHM presented in all the probands and in 11/14 affected family members, suggesting that it is a more common indicator of STL than the previously described vitreoretinal abnormalities, especially in children. The rate of STL diagnosis could increase from 25.0% to 66.7% for probands and from 50.0% to 92.9% for affected family members if eoHM, PVD/FH, and HJ are added to the diagnostic criteria. Conclusions: In summary, it is not easy to differentiate STL from eoHM with routine ocular examination in outpatient clinics. Awareness of atypical phenotypes and newly recognized signs may be of help in identifying atypical STL, especially in children at eye clinics.