Ocular and Systemic Findings in COL2A1 and COL11A1 Stickler Syndrome

Abstract

Purpose:

Stickler syndrome is most commonly caused by variants in COL2A1 and COL11A1 genes. Our purpose was to describe genetic variants and phenotypes in COL2A1 and COL11A1 Stickler syndrome.

Methods:

Retrospective genotype-phenotype evaluation of COL2A1 and COL11A1 Stickler syndrome subjects.

Results:

Thirty-two subjects with COL2A1 and 13 subjects with COL11A1 Stickler syndrome were last seen at a mean age of 17.2 ± 13.1 and 12.6 ± 3.8 years respectively (p = 0.08). We found that 50% of COL2A1 subjects had lattice degeneration, whereas 8% of the COL11A1 subjects had lattice degeneration (p=0.015). The most common type of variant for COL2A1 Stickler syndrome was a premature termination codon (12 out of 18 families, 67%), and the most common types of variants for COL11A1 Stickler syndrome were glycine missense variants (4 out of 10 families, 40%) and splice site variants (4 out of 10, 40%).

Discussion:

There was a higher rate of lattice degeneration in COL2A1 patients compared to COL11A1 patients, a finding that could be influenced by a trend towards older age at last follow up in the COL2A1 group.

Summary Statement:

Lattice degeneration is more prevalent in COL2A1 Stickler syndrome compared to COL11A1 Stickler syndrome. Nonsense variants are more common in COL2A1 and glycine missense variants are more common in COL11A1.

Introduction

Stickler syndrome is a hereditary disorder causing ocular, maxillofacial, auditory, and musculoskeletal abnormalities (Stickler et al., 1965). Type 1 and type 2 Stickler syndromes are the most frequent types and the focus of this study. Type 1 Stickler syndrome is due to autosomal dominant inherited pathogenic variants in the COL2A1 gene encoding type II collagen (OMIM #108300) and is the most common type. Type 2 Stickler syndrome is due to autosomal dominant inherited pathogenic variants in the COL11A1 gene encoding type XI collagen (OMIM #604841) and represents 10-20% of Stickler syndrome cases (Annunen et al., 1999; Choi et al., 2021).

Ocular findings in Stickler syndrome include early onset high myopia, presenile cataracts, glaucoma, lattice degeneration, vitreous abnormalities, and retinal detachment (Parma et al., 2002). Significant morbidity occurs in Stickler syndrome due to retinal detachment, which typically occurs prior to age 20 (Carpenter et al., 2025). We recently published a systematic review and meta-analysis which found the relative risk of retinal detachment is 1.78 times higher in COL2A1 compared to COL11A1 Stickler syndrome patients (Carpenter et al., 2025), highlighting the importance of evaluating the phenotypic and genetic differences between Stickler syndrome types.

Our primary goal in this retrospective study was to describe the genotype and phenotype of patients with COL2A1 and COL11A1 Stickler syndrome.

Methods

Subject Selection

Subjects seen in ophthalmology clinics at the University of Utah between 2010 and 2025 were screened using the ICD-10 code Q89.8. The study was approved by the University of Utah Institutional Review Board with a waiver of informed consent and followed the tenets of the Declaration of Helsinki.

There was complete and consecutive inclusion of patients meeting at least one of the following criteria: 1) a pathogenic or likely pathogenic variant in COL2A1 or COL11A1, 2) a variant of uncertain significance in COL2A1 or COL11A1 and at least two clinical manifestations of Stickler syndrome, or 3) a personal history of at least two clinical manifestations of Stickler syndrome and a first degree relative with a pathogenic or likely pathogenic variant in COL2A1 or COL11A1. Clinical manifestations of Stickler syndrome included any characteristic facial abnormality, (Meurice et al., 2025) characteristic musculoskeletal abnormalities (Rehm et al., 2025), any hearing deficit, as well as suggestive ocular findings such as premature cataracts, ocular hypertension, vitreous abnormalities, lattice degeneration, and retinal tear or detachment. Subjects with a clinical phenotype of spondyloepiphyseal dysplasia congenita were excluded since its molecular pathology and clinical phenotype are distinct from Stickler syndrome (Zhang et al., 2020). No subjects were found to have Stickler syndrome caused by variants in the less common genes (COL11A2, COL9A1, COL9A2, and COL9A3).

Genotype Analysis

We reviewed genetic tests performed during routine clinical care by multiple facilities. Since test results were reported in various versions of reference complementary DNA (cDNA) transcripts, we used EMBOSS Stretcher version 6.6.0 (Madeira) to convert variant cDNA nomenclature to the current reference transcript when needed (NM_001844.5 for COL2A1 and NM_001854.4 for COL11A1). Position one corresponds to the A of the ATG start codon. We reported genomic variants in GRCh37/hg19. ClinVar (Landrum et al., 2018), gnomAD (Wang et al., 2020) and dbSNP (Smigielski et al., 2000) databases for each variant. Expected protein changes were determined using Ensembl (Howe et al., 2021). Variant pathogenicity was categorized according to the American College of Medical Genetics and Genomics, Association for Molecular Pathology, and College of American Pathologists joint guidelines (S. Richards et al., 2015) using the Franklin by Genoox app (https://franklin.genoox.com), an artificial intelligence-based interpretation engine with application to rare diseases such as Stickler syndrome (Rodrigues et al., 2022).

Phenotype Analysis

For each subject, we reviewed the results of a complete history and physical and made note of the following facial abnormalities: glossoptosis, micrognathia, cleft palate, flat midfacial region, and bifid uvula. We included all types of hearing loss (sensorineural, conductive, and mixed). We included musculoskeletal abnormalities such as joint pain and hypermobility, metaphyseal-epiphyseal dysplasia, campylodactyly, genu valgum, pectus carinatum, and kyphoscoliosis.

We reviewed records of ophthalmic examinations to determine ocular features of Stickler syndrome. Myopia was defined as spherical equivalent more myopic than −0.50 D in at least one eye and high myopia as spherical equivalent more myopic than −6.00 D in at least one eye in a phakic patient (Flitcroft et al., 2019). Visual acuity was obtained with usual correction. Ocular hypertension was defined as intraocular pressure greater than 21 mmHg on more than one occasion before or more than 90 days after intraocular surgery (Kass et al., 2002). Any cataract not attributable to another known cause (trauma, intraocular surgery, steroids) prior to age 60 was included. Vitreous abnormalities included the membranous and beaded phenotypes (A. J. Richards et al., 2010), vitreous syneresis advanced for age, vitreous veils, and optically empty vitreous without a history of vitrectomy. The presence of any lattice degeneration in one or both eyes was noted by review of records, as fundus photographs were not available for every patient. The presence or absence of lattice degeneration in eyes that presented with retinal detachment repair was not recorded as this may have been obscured by post-surgical changes. Unfortunately, most patient records did not distinguish between perivascular lattice and peripheral lattice degeneration. We recorded the number of patients in each group with retinal detachment and prophylactic cryopexy or laser retinopexy treatment. We compared the age at last follow up for patients presenting with and without ocular and systemic manifestations of Stickler syndrome.

Statistical Analysis

Our initial plan was to compare retinal detachment rates between groups, but based on a review of the data, we performed post-hoc statistical comparisons of multiple ocular and systemic manifestations of Stickler syndrome. Statistical analysis was performed using GraphPad Prism Version 9.3.1 (GraphPad Software, San Diego, California, USA). For group comparisons, categorical variables were compared using a chi-square test, or Fisher's exact test, as appropriate. For continuous variables, an independent samples Student t test was used.

Results

Subject Characteristics

Thirty-two subjects with COL2A1 Stickler syndrome from 18 families were included in the analysis. Thirteen patients with COL11A1 Stickler syndrome from 10 families were included in analysis. The mean age at last follow-up visit was 17.2 years (SD: 13.1, IQR: 8.4 - 21.4) for COL2A1 Stickler syndrome and 12.6 years (SD: 3.8, IQR: 9.8 - 16.6) for COL11A1 Stickler syndrome (Table 1). The mean length of follow-up was 6.9 years (SD 5.5, IQR: 1.9-9.7) for COL2A1 Stickler syndrome and 10.1 (SD 5.0, IQR 7.3 - 14.7) for COL11A1 Stickler syndrome (Table 1). There was no significant difference between the two groups in age at last follow-up (p=0.08) or length of follow-up (p=0.07).

Table 1.

Patient demographics and follow up.

	COL2A1 Stickler syndrome subjects (n=32)	COL11A1 Stickler syndrome subjects (n=13)	Odds ratio (95% CI) with reference to COL2A1	P-value
Sex assigned at birth
Male	12/32 (38%)	7/13 (54%)	0.51 (0.11, 2.30)	0.34
Female	20/32 (62%)	6/13 (46%)
Race†
White/Caucasian	28/31 (90%)	11/13 (85%)	2.54 (0.03, 206.79)	0.50
Asian	1/31 (3%)	1/13 (8%)
Ethnicity†
Hispanic/Latino	2/31 (6%)	1/13 (8%)	0.80 (0.04, 51.08)	1.00
Non-Hispanic/Latino	30/31 (97%)	12/13 (92%)
Follow up data
Age at last follow up, mean ± standard deviation in years	17.2 ± 13.1	12.6 ± 3.8		0.08
Length of follow up, mean ± standard deviation in years	6.9 ± 5.5	10.1 ± 5.0		0.07

^†race and ethnicity were unavailable for one patient

Ocular Phenotypes

We report the frequency of ocular findings in Stickler syndrome subtypes in Table 2. Myopia was the most common ocular finding in both COL2A1 and COL11A1 subjects. Other findings include glaucoma/ocular hypertension, presenile cataracts, and vitreous abnormalities. There was no statistically significant difference in retinal detachment rate between Stickler subtypes. There was, however, a statistically significant difference in the rates of lattice degeneration with higher rates among COL2A1 compared to COL11A1 patients. In addition to comparing lattice degeneration rates per patient, we compared the number of COL2A1 families with lattice degeneration (13 families, 72%) to the number of COL11A1 families with lattice degeneration (1 family, 10%) (OR, 23 [95% CI, 2-1101; p=0.002]. Individuals in both groups underwent either no prophylaxis, prophylactic cryopexy, or prophylactic laser retinopexy based on parental, patient, or physician preference. The majority of patients underwent some form of prophylactic therapy. Individual subject data for COL2A1 and COL11A1 subjects including ocular findings are available in Supplemental Tables 1 and 2, respectively.

Table 2.

Systemic and ocular findings of Stickler patients.

	COL2A1 Stickler syndrome subjects (n=32)	COL11A1 Stickler syndrome subjects (n=13)	Odds ratio (95% CI) with reference to COL2A1	P-value
Systemic findings
Facial abnormalities	18/32 (56%)	9/13 (69%)	0.57 (0.11, 2.64)	0.42
Hearing loss	16/32 (50%)	9/13 (69%)	0.44 (0.08, 2.05)	0.24
Musculoskeletal abnormalities	16/32 (50%)	9/13 (69%)	0.44 (0.08, 2.05)	0.24
Ocular findings
High myopia	20/31 (65%)	7/13 (54%)	1.56 (.34, 7.00)	0.50
Myopia †	30/31 (97%)	10/13 (77%)	9.0 (0.60, 4.87)	0.07
Glaucoma/Ocular hypertension	7/32 (22%)	4/13 (31%)	0.63 (0.12, 3.69)	0.53
Presenile Cataracts	10/32 (31%)	7/13 (54%)	0.39 (0.08, 1.79)	0.15
Vitreous abnormalities	16/32 (50%)	4/13 (31%)	2.25 (0.49, 11.9)	0.24
Lattice degeneration	16/32 (50%)	1/13 (8%)	12.0 (1.39, 5.44)	0.02
Retinal detachment	8/32 (25%)	2/13 (15%)	1.83 (0.29, 20.3)	0.70
Prophylaxis
Cryopexy	4/32 (13%)	1/13 (8%)	1.71 (0.15, 91)	1.00
Laser retinopexy	15/32 (47%)	6/13 (46%)	1.03 (0.23, 4.63)	0.96

^†One COL2A1 subject was missing refractive data

Systemic Phenotypes

We report the frequency of systemic findings of Stickler syndrome subtype in Table 2. We recorded systemic manifestations of Stickler syndrome including facial abnormalities, hearing loss, and musculoskeletal abnormalities. Between COL2A1 and COL11A1 subjects we found no statistically significant differences in systemic manifestations of Stickler. Individual subject data including systemic findings for COL2A1 and COL11A1 subjects are available in Supplemental Tables 1 and 2, respectively.

Age at Last Follow Up and Phenotypic Manifestations

Because some ocular and systemic manifestations of Stickler syndrome have increased incidence with age, we compared the age at last follow up for those presenting with versus without manifestations of Stickler syndrome, as can be seen in Table 3. For several manifestations, the age of individuals with and those without manifestations differed. Individuals with lattice degeneration and retinal detachment were significantly older at last follow up than those without.

Table 3.

Age at last follow up for COL2A1 and COL11A1 Stickler syndrome patients presenting with and without each phenotypic manifestation.

	Mean age ± SD with phenotype	Mean age ± SD without phenotype	P-value
Facial abnormalities	13 ± 9	20 ± 13	0.04
Hearing loss	14 ± 9	14 ± 14	0.23
MSK† abnormalities	17 ± 9	14 ± 14	0.49
High Myopia	18 ± 12	10 ± 5	0.003
Glaucoma / OHTN‡	19 ± 15	15 ± 10	0.4
Cataracts	23 ± 13	12 ± 8	0.004
Vitreous abnormalities	21 ± 14	12 ± 8	0.02
Lattice Degeneration	21 ± 13	13 ± 9	0.02
Retinal Detachment	25 ± 14	13 ± 9	0.04

Genetic Variants

Each of the 18 COL2A1 Stickler syndrome families included in this series had a different variant in COL2A1 causing premature termination codons, splicing abnormalities, or glycine missense variants (Table 4). Each of the 10 COL11A1 Stickler syndrome families had a different variant in COL11A1causing glycine missense variants, splice site variants, or large deletions (Table 5).

Table 4.

COL2A1 variants causing COL2A1 Stickler syndrome.

Variant number	Variant	Protein change	ClinVar	gnomAD	dbSNP	ACMG criteria	Variant classification
1	c.2759del	p.(Pro920Leufs*108)	VCV001451162	n/a	n/a	PM2, PVS1	pathogenic
2	c.1732del	p.(Ser578Leufs*51)	n/a	n/a	n/a	PM2, PVS1	likely pathogenic
3	c.1221+1G>A	abnormal splicing	VCV000866010	n/a	rs1399741348	PM2, PVS1, PP3	pathogenic
4	c.86-12C>G	abnormal splicing	VCV000866010.13	n/a	n/a	PM2, PS2, PP3	variant of uncertain significance
5	c.156C>A	p.(Cys52*)	VCV000547245	n/a	rs1246771678	PM2, PVS1	pathogenic
6	c.1043del	p.(Gly348Valfs*281)	VCV001074778	n/a	n/a	PM2, PVS1	pathogenic
7	c.3896G>A	p.(Trp1299*)	VCV001213981	n/a	n/a	PM2, PVS1	pathogenic
8	c.3167del	p.(Gly1056Valfs*74)	n/a	n/a	n/a	PM2, PVS1	likely pathogenic
9	c.2076del	p.(Gly693Alafs*95)	n/a	n/a	n/a	PM2, PVS1	likely pathogenic
10	c.3004-1G>A	abnormal splicing	VCV001218409	n/a	n/a	PM2, PVS1, PP3	pathogenic
11	c.85+1G>A	abnormal splicing	VCV001493942.6	n/a	rs727503882	PM2, PVS1, PP3	pathogenic
12	c.718G>T	p.(Gly240Cys)	n/a	n/a	n/a	PM2, PM5, PP2, PP3	likely pathogenic
13	c.2200del	p.(Ser734Leufs*54)	VCV002125721.2	n/a	n/a	PM2, PVS1	pathogenic
14	c.2381del	p.(Pro794Leufs*87)	VCV000547258.11	n/a	rs1555166218	PM2, PVS1	pathogenic
15	c.4068dupC	p.(F1357Lfs*8)	n/a	n/a	n/a	PM2, PVS1	pathogenic
16	c.2551C>T	p.(Gln851*)	n/a	n/a	n/a	PM2, PVS1	likely pathogenic
17	c.86-1G>C	abnormal splicing	RCV002894373.2†	n/a	rs2540187950	PM2, PVS1, PP3	likely pathogenic‡
18	c.491del	p.(Pro164Leufs*35)	VCV000689620.14	n/a	n/a	PM2, PVS1	likely pathogenic

^†single report of the patient from our study

^‡variants in the propeptide domain have been associated with Stickler syndrome (Demal et al., 2022; Zhang et al., 2020)

Table 5.

COL11A1 variants causing COL11A1 Stickler syndrome.

Variant number	Variant	Protein change	ClinVar	gnomAD	dbSNP	ACMG Criteria	Variant classification
1	c.2916+1G>T	abnormal splicing	n/a	n/a	n/a	PM2, PVS1, PP3	pathogenic
2	c.3438+2T>G	abnormal splicing	VCV001483707	n/a	n/a	PM2, PVS1, PP3	likely pathogenic
3	c.4537G>A	p.(Gly1513Ser)	VCV001986405.2	n/a	n/a	PM1, PM3, PM5, PP3	likely pathogenic
4	g.103454247_103493232del	Deletion of exons 6 to 29	n/a	n/a	n/a	PP1-M, PVS1	pathogenic
5	c.1622G>A	p.(Gly541Asp)	VCV002131957.2	n/a	n/a	PM1, PM2, PP3	variant of uncertain significance
6	c.4456G>A	p.(Gly1486Arg)	n/a	n/a	n/a	PM1, PM2, PP3	likely pathogenic
7	c.1955G>A	p.(Gly652Asp)	n/a	n/a	n/a	PM2, PP3	variant of uncertain significance
8	c.3276+1G>A	abnormal splicing	n/a	n/a	n/a	PVS1, PM3, PP3	likely pathogenic
9	deletion of exons 21-24, exact breakpoints unknown	in frame deletion of exons 21-24	n/a	n/a	n/a	None applied	variant of uncertain significance
10	c.1900-2A>G	abnormal splicing	VCV002753566.2†	n/a	n/a	PVS1, PM2, PP3	likely pathogenic‡

^†single report of the patient from our study

^‡a variant in this splice site has previously been associated with Stickler syndrome (Richards et al., 2006)

Discussion

We examined phenotypes of patients with COL2A1 and COL11A1 Stickler syndrome during a median follow up period of 6.2 and 9.3 years, respectively. Rates of some ocular manifestations of Stickler syndrome were similar between the two genotypes, including high rates of myopia and low rates of glaucoma/ocular hypertension in both groups. Vitreous abnormalities and presenile cataract rates were variable between the groups. A notable difference was that COL2A1 subjects had a statistically higher rate of lattice degeneration compared to COL11A1 subjects. We found that rates of systemic features including facial, joint, and skeletal abnormalities and hearing loss were also variable between the two Stickler types. Most of the COL2A1 Stickler syndrome variants resulted in premature termination codons (67%), whereas COL11A1 variants resulted more commonly in glycine substitutions (40%) and splice site alterations (40%).

The differing prevalence of variant types in our series likely reflects the different roles of the two collagen types within the vitreous collagen fibril. Collagen II composes the majority of the fibril, whereas collagen V/XI is a minor component that regulates fibril diameter (Bishop, 2000; Sun et al., 2020). Given the different roles for the two gene products, a missense mutation and/or reduced expression of COL2A1 is unlikely to be functionally equivalent to a similar mutation in COL11A1. The high prevalence of premature termination codons in COL2A1 variants is consistent with previous literature suggesting that reduced gene expression due to nonsense mediated decay is a common mechanism of COL2A1 Stickler syndrome (A. J. Richards et al., 2006). By contrast, glycine missense variants in COL2A1 more commonly cause severe musculoskeletal diseases such as spondylepiphyseal dysplasia and achrondrogenesis, which can be distinguished from Stickler syndrome by characteristics such as dwarfism and perinatal lethality (Demal et al., 2022; Zhang et al., 2020). We included one COL2A1 subject with a glycine missense variant who was clinically diagnosed with Stickler syndrome due to lack of dwarfism.

In contrast, glycine missense variants were prevalent in our COL11A1 subjects. The amino acid sequence of collagens contains glycine at every third residue, which permits tight packing of the collagen triple helix. Although some of the glycine missense variants in COL11A1 were classified as variants of uncertain significance by the ACMG guidelines, glycine missense mutations in triple helix domains are well known to disrupt protein folding (Cheng et al., 2011), and in each case, the variant segregated with disease within the family. Variant nine, a large in-frame deletion in COL11A1, was also classified as a variant of uncertain significance, but segregated with disease in the family. The prevalence of glycine missense variants suggests that a dominant negative effect due to incorporation of an abnormal polypeptide chain in the collagen triple helix may be a disease mechanism of COL11A1 Stickler syndrome (Soh et al., 2022).

The difference in functional roles between the genes, as well as the difference in variant types could potentially explain our finding of higher rates of lattice degeneration in COL2A1 subjects in our cohort. Another possible confounder is age, since patients with lattice degeneration were older than those without in our study population. Although COL2A1 patients tended to be older than COL11A1 patients, this was non-significant (p=0.08). In the general population, lattice degeneration can be seen in 30% of eyes with retinal detachment (Burton, 1989) compared to 12% of eyes without retinal detachment (Foos & Simons, 1984). In fellow eyes of patients with unilateral retinal detachment, lattice degeneration significantly increases the risk of a second-eye retinal detachment (Wallsh et al., 2023) and may be an indication for prophylactic treatment of the lattice degeneration. Lattice degeneration is thought to cause retinal detachment from strong vitreo-retinal adhesion causing a retinal tear (Maltsev et al., 2022) during posterior vitreous detachment. It is unknown whether lattice degeneration, which is more commonly found in COL2A1 subjects in our cohort, predisposes patients with Stickler syndrome to retinal detachment in a similar manner. A large prospective study would likely be required to investigate whether lattice degeneration increases risk of retinal detachment in Stickler syndrome.

Radial perivascular lattice degeneration and circumferential lattice degeneration have been reported in COL2A1 and COL11A1 Stickler syndrome (Parma et al., 2002; Poulson, 2004; Vu et al., 2003). In an Ovid Medline literature search using the terms Stickler and lattice on November 15, 2025, we found no prior studies describing a difference in rates of lattice degeneration between COL2A1 and COL11A1 Stickler syndrome types. We found two studies that evaluated rates of lattice degeneration in both Stickler types. Choi et al. found lattice degeneration in 75% of COL2A1 patients and 64% of COL11A1 patients with no statistically significant difference between the two groups (Choi et al., 2021). Kandeeban et al. described similar rates without a significant difference between the two groups (Kandeeban et al., 2022). The differences in lattice degeneration found in our study compared to the aforementioned literature could be the result of differences in the number of families represented and/or differences in age distribution between studies, since lattice degeneration prevalence increases from the first to the second decade of life (Yura, 1998). Given the limitations of this study, our finding of higher lattice degeneration rates in COL2A1 Stickler syndrome needs to be replicated. In addition, a larger study is necessary to further evaluate the impact of age on rates of lattice degeneration in COL2A1 and COL11A1 Stickler patients. A few recent studies have highlighted phenotypic differences between COL2A1 and COL11A1 Stickler syndrome, but did not report on the presence or absence of lattice degeneration (Constant et al., 2026; Drackley et al., 2025). Since this is a retrospective study, vitreous abnormalities may be under-reported.

This study is the first to demonstrate a significantly higher rate of lattice degeneration in COL2A1 Stickler syndrome compared to COL11A1 Stickler syndrome. Our prior individual patient data meta-analysis found a higher rate of retinal detachment in COL2A1 Stickler syndrome compared to COL11A1 Stickler syndrome (Carpenter et al., 2025), a finding which was not replicated in the current study. This discrepancy could be explained by the relatively lower age at last follow up in our cohort compared to the meta-analysis subjects. In addition, because most studies are not population-based designs, there is likely to be some degree of referral bias affecting the recorded retinal detachment rates.

This study has several limitations including limited sample size and retrospective design. Some individuals in our study including parents or extended family members may be receiving care outside of our institution, which could underestimate the number of affected individuals per family and influence generalizability of our results. Since the patients were included based on eye clinic records, the prevalence of ocular conditions in our cohort is likely higher than in the general population of all Stickler syndrome patients. We anticipate that reporting of ocular conditions was similar in both groups, allowing for a relative comparison of the rates of lattice degeneration. The rate of retinal detachment may be an under-estimate since the average age at last follow up was 13 years, and many retinal detachments occur prior to age 20 (Carpenter et al., 2025). Similarly, many of our patients underwent prophylactic treatment, which influences retinal detachment rates. Due to the retrospective nature of this study, we were unable to consistently differentiate between peripheral/circumferential and radial lattice degeneration.

Conclusion

In this retrospective chart review we evaluated phenotypic and genotypic features of COL2A1 and COL11A1 Stickler syndrome. Genetic variants in COL2A1 often result in premature termination codons, whereas genetic variants in COL11A1 often result in glycine missense mutations, likely reflecting the different roles of the two proteins in vitreous collagen fibrils. We found the rate of lattice degeneration was higher in COL2A1 compared to COL11A1 subjects (p=0.015). Larger studies will be required to determine the clinical significance of this finding. Because lattice degeneration is a risk factor for retinal detachment, a future investigation into the correlation between higher rates of lattice degeneration and retinal detachment in COL2A1 subjects compared to COL11A1 subjects is warranted.

Data availability statement

Individual patient data is available in supplemental tables 1 and 2.