Early-Onset Ocular Presentation in Stickler Syndrome Type 1 Due to a COL2A1 Frameshift Variant.
PMID 41715899 | PMCID PMC12930911 | DOI 10.12659/AJCR.951257 · The American journal of case reports · 2026
BACKGROUND Stickler syndrome is a genetically heterogeneous connective tissue disorder caused by mutations in collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2). It is characterized by a distinctive craniofacial appearance, high myopia, vitreoretinal degeneration, hearing loss, and early-onset arthritis. Type 1, the most common autosomal-dominant form, results from COL2A1 variants and is strongly associated with ocular complications, including high myopia, vitreous degeneration, and retinal detachment. Early recognition of systemic and ocular findings is essential for timely management and genetic counseling. CASE REPORT An 8-year-old Saudi girl presented to the emergency department with sudden deterioration of vision in the right eye. External examination revealed midfacial hypoplasia. Ophthalmologic evaluations, including best-corrected visual acuity measurement, fundus photography, optical coherence tomography, and genetic testing, were performed. Rhegmatogenous retinal detachment was identified and surgically managed. Revision surgery was performed; at 3 years post-revision, best-corrected visual acuity in the right eye had improved to 20/30. The family history included childhood retinal detachment in the patient's father. Clinical exome sequencing identified a novel heterozygous COL2A1 frameshift variant, c.3642delT (p.Gly1215Alafs*12), that introduced a premature stop codon; Sanger sequencing confirmation and segregation analysis were consistent with pathogenicity. CONCLUSIONS This report describes a previously undocumented COL2A1 frameshift variant causing Stickler syndrome type 1. The truncating mutation may be associated with the early-onset, ocular-predominant presentation observed in the present case. This variant expands the known COL2A1 mutational spectrum and underscores the importance of molecular testing for accurate diagnosis and family counseling in pediatric collagenopathies.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | COL2A1 | “Early-Onset Ocular Presentation in Stickler Syndrome Type 1 Due to a COL2A1 Frameshift Variant.” | 0.98 | hgnc_dict_v1 |
| gene | COL11A1 | “BACKGROUND Stickler syndrome is a genetically heterogeneous connective tissue disorder caused by mutations in collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2).” | 0.98 | hgnc_dict_v1 |
| gene | COL11A2 | “BACKGROUND Stickler syndrome is a genetically heterogeneous connective tissue disorder caused by mutations in collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2).” | 0.98 | hgnc_dict_v1 |
| gene | COL9A1 | “BACKGROUND Stickler syndrome is a genetically heterogeneous connective tissue disorder caused by mutations in collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2).” | 0.98 | hgnc_dict_v1 |
| gene | COL9A2 | “BACKGROUND Stickler syndrome is a genetically heterogeneous connective tissue disorder caused by mutations in collagen genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2).” | 0.98 | hgnc_dict_v1 |
| phenotype | hearing loss | “It is characterized by a distinctive craniofacial appearance, high myopia, vitreoretinal degeneration, hearing loss, and early-onset arthritis.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “CASE REPORT An 8-year-old Saudi girl presented to the emergency department with sudden deterioration of vision in the right eye.” | 0.95 | saudi_context_rules_v1 |
| variant | c.3642delT | “Clinical exome sequencing identified a novel heterozygous COL2A1 frameshift variant, c.3642delT (p.Gly1215Alafs*12), that introduced a premature stop codon; Sanger sequencing confirmation and segregation analysis were consistent with pathogenicity.” | 0.95 | hgvs_regex_v1 |