UNASSIGNED: Stickler syndrome is a hereditary connective tissue disorder associated with ocular, orofacial, musculoskeletal, and auditory impairments. Its main clinical characteristics include retinal detachment, hearing loss, and midface underdevelopment. In clinical practice, macrocyst is rarely reported in retinal detachment cases with Stickler syndrome.
UNASSIGNED: We report the case of a 7-year-old child who developed a rhegmatogenous retinal detachment (RRD) in the right eye, accompanied by multiple peripheral macrocysts. The detachment was successfully surgically repaired with vitrectomy, retinal laser photocoagulation, cryotherapy and silicone oil tamponade. During the operation, a mini-retinectomy in the outer layer of each macrocyst was made for vesicular drainage and retinal reattachment. Genetic testing identified a pathogenic point mutation variant (c.1693C>T; p.Arg565Cys) in exon 26 of the COL2A1 gene. Six-months after the operation, the retina remained attached with improvement of best corrected visual acuity to 20/200.
UNASSIGNED: Patients with Stickler syndrome may develop RRD of different severity. Macrocyst is rarely reported in previous literature of Stickler syndrome. In this case report, we share our experience in treating with multiple macrocysts in RRD and emphasize the importance of periodic follow-up for patients with Stickler syndrome.

Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for these patients. Systemic findings are also common, with craniofacial, skeletal, and auditory systems often involved. SS is genotypically and phenotypically heterogenous, which can make recognizing and correctly diagnosing individuals difficult. Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members. Here we review common clinical manifestation of SS and genetic tests frequently ordered as part of the SS evaluation.

Stickler syndrome is a collagenopathy caused by mutations in the genes COL2A1 (STL1) or COL11A1 (STL2). Affected patients manifest ocular, auditory, articular, and craniofacial manifestations in varying degrees. Ocular symptoms include myopia, retinal detachment, cataract, and glaucoma. The aim of this systematic review was to evaluate the prevalence of ocular manifestations and the outcome of prophylactic treatment on reducing the risk of retinal detachment.
A systematic literature search was performed in the PubMed database. Information on the cross-study prevalence of myopia, retinal detachment, cataract, glaucoma, visual impairment, severity and age of onset of myopia and retinal detachments. Studies that reported on the outcome of prophylactic treatment against a control group were explored.
37 articles with 2324 individual patients were included. Myopia was found in 83% of patients, mostly of a moderate to severe degree. Retinal detachments occurred in 45% of patients. Generally, the first detachment occurred in the second decade of life in STL1 patients and later in STL2. Cataracts were more common in STL2 patients, 59% versus 36% in STL1. Glaucoma (10%) and visual impairment (blind: 6%; vision loss in one eye: 10%) were rare. Three studies reported on the effect of prophylactic treatment being protective.
Ocular manifestations are common in Stickler patients, but the comparison between studies was difficult because of inconsistencies in diagnostic and inclusion criteria by different studies. Sight-threatening complications such as retinal detachments are common but although prophylactic therapy is reported to be effective in retrospective studies, evidence from randomized trials is missing.

Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present.
By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1.
There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found.
Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.

BACKGROUND: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome.
METHODS: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp).
CONCLUSIONS: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

Pierre Robin sequence (PRS) is an important craniofacial anomaly that can be seen as an isolated finding or manifestation of multiple syndromes. 22q11.2 deletion and Stickler syndrome are cited as the two most common conditions associated with PRS, but their frequencies are debated. We performed a retrospective study of 66 patients with PRS and reviewed their genetic testing, diagnoses, and clinical findings. The case series is complemented by a comprehensive literature review of the nature and frequency of genetic diagnosis in PRS. In our cohort 65% of patients had associated anomalies; of these, a genetic diagnosis was established in 56%. Stickler syndrome was the most common diagnosis, comprising approximately 11% of all cases, followed by Treacher Collins syndrome (9%). The frequency of 22q11.2 deletion was 1.5%. Chromosome arrays, performed for 72% of idiopathic PRS with associated anomalies, revealed two cases of 18q22→qter deletion, a region not previously reported in association with PRS. A review of the cytogenetic anomalies identified in this population supports an association between the 4q33-qter, 17q24.3, 2q33.1, and 11q23 chromosomal loci and PRS. We found a low frequency of 22q11.2 deletion in PRS, suggesting it is less commonly implicated in this malformation. Our data also indicate a higher frequency of cytogenetic anomalies in PRS patients with associated anomalies, and a potential new link with the 18q22→qter locus. The present findings underscore the utility of chromosomal microarrays in cases of PRS with associated anomalies and suggest that delaying testing for apparently isolated cases should be considered.