Severe foveal hypoplasia and macular degeneration in Stickler syndrome caused by missense mutation in COL2A1 gene

Ophthalmic Genet. 2022 Aug;43(4):508-512. doi: 10.1080/13816810.2022.2068044. Epub 2022 Apr 26.


Background: The aim is to determine the retinal changes in patients with Stickler syndrome caused by a p.R565C missense mutation of the COL2A1 gene.

Methods: We reviewed the clinical records of 10 eyes of six patients from two families with the Stickler syndrome. The members of both families were heterozygous for the p.R565C mutation. The clinical features including the visual acuity, fundus appearances, fundus autofluorescence (FAF), optical coherence tomographic (OCT) images, and electroretinograms were examined.

Results: Myopia of -12 diopters (D) to -24 D with an average of -16.8 D was observed in 9 eyes of the 5 patients. The FAF images showed different degrees of hyper and hypoautofluorescent patterns in the macula in all but the two youngest patients (7 of 9 eyes, 78%). The OCT images showed the absence of a foveal pit and destruction of the outer retinal layers in the macular area in all patients. The ellipsoid zone (EZ) in the macular region was disrupted in eight eyes (80%) of which seven were fovea sparing.

Conclusion: Two families with Stickler syndrome with the p.R565C mutation showed more severe foveal hypoplasia, macular degeneration, and extensive retinal degeneration. A correlation of the OCT and FAF images with the genotype is helpful in determining the prognosis of Stickler syndrome.

Keywords: COL2A1; Stickler syndrome; foveal hypoplasia; macular degeneration.

MeSH terms

  • Arthritis
  • Collagen Type II* / genetics
  • Connective Tissue Diseases / genetics
  • Eye Diseases, Hereditary* / genetics
  • Fluorescein Angiography
  • Fovea Centralis
  • Fundus Oculi
  • Hearing Loss, Sensorineural
  • Humans
  • Macular Degeneration* / genetics
  • Mutation, Missense
  • Osteochondrodysplasias* / genetics
  • Retinal Detachment* / diagnosis
  • Retinal Detachment* / genetics
  • Tomography, Optical Coherence
  • Vision Disorders


  • COL2A1 protein, human
  • Collagen Type II

Supplementary concepts

  • Stickler syndrome, type 1