We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Medical Genetics Nemocnice České Budějovice České Budějovice Czech Republic

Department of Ophthalmology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Ophthalmology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

DNA Laboratory Department of Child Neurology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

GENNET Liberec Czech Republic

Molecular Biology AGEL Laboratories Nový Jičín Czech Republic

Reprofit International Brno Czech Republic

Research Unit for Rare Diseases Department of Paediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

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Long-term anatomical and functional outcomes of surgical treatment of retinal complications in children and adolescents with Stickler syndrome between 2004 and 2021