Stickler Syndrome: Airway Complications in a Case Series of 502 Patients.

BACKGROUND: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and complications in a nonselected series of Stickler syndrome cases. To our knowledge, this is the largest such series in the published literature. METHODS: We retrospectively identified patients with genetically confirmed Stickler syndrome who had undergone general anesthesia in a major teaching hospital, seeking to identify factors that predicted patients who would require more than 1 attempt to correctly site an endotracheal tube (ETT) or supraglottic airway device (SAD). Patient demographics, associated factors, and anesthetic complications were collected. Descriptive statistical analysis and logistic regression modeling were performed. RESULTS: Five hundred and twoanesthetic events were analyzed. Three hundred ninety-five (92.7%) type 1 Stickler and 63 (96.9%) type 2 Stickler patients could be managed with a single attempt of passing an ETT or SAD. Advanced airway techniques were required on 4 occasions, and we report no major complications. On logistic regression, modeling receding mandible (P = .0004) and history of cleft palate (P = .0004) were significantly associated with the need for more than 1 attempt at airway manipulation. CONCLUSIONS: The majority of Stickler patients can be anesthetized safely with standard management. If patients have a receding mandible or history of cleft, an experienced anesthetist familiar with Stickler syndrome should manage the patient. We recommend that patients identified to have a difficult airway wear an alert bracelet.

Deep Intronic Sequence Variants in COL2A1 Affect the Alternative Splicing Efficiency of Exon 2, and May Confer a Risk for Rhegmatogenous Retinal Detachment.

COL2A1 mutations causing haploinsufficiency of type II collagen cause type 1 Stickler syndrome that has a high risk of retinal detachment and failure of the vitreous to develop normally. Exon 2 of COL2A1 is alternatively spliced, expressed in the eye but not in mature cartilage and encodes a region that binds growth factors TGFß1 and BMP-2. We investigated how both an apparently de novo variant and a polymorphism in intron 2 altered the efficiency of COL2A1 exon 2 splicing and how the latter may act as a predisposing risk factor for the occurrence of posterior vitreous detachment (PVD)-associated rhegmatogenous retinal detachment (RRD) in the general population. Using amplification of illegitimate transcripts and allele-specific minigenes expressed in cultured cells, we demonstrate variability in exon 2 inclusion not only between different control individuals, but also between different COL2A1 alleles. We identify transacting factors that bind to allele-specific RNA sequences, and investigate the effect of knockdown and overexpression of these factors on exon 2 splicing efficiency. Finally, using a specific cohort of patients with PVD-associated RRD and a control population, we demonstrate a significant difference in the frequency of the COL2A1 intronic variant rs1635532 between the two groups.

Prevention of retinal detachment in Stickler syndrome: the Cambridge prophylactic cryotherapy protocol.

PURPOSE: The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to prevent retinal detachment arising from giant retinal tears in type 1 Stickler syndrome. DESIGN: Retrospective comparative case series. PARTICIPANTS: Four hundred eighty seven patients with type 1 Stickler syndrome. METHODS: Time to retinal detachment was compared between patients who received bilateral prophylaxis and untreated controls, with and without individual patient matching. Patients receiving unilateral prophylaxis (after fellow eye retinal detachment) were similarly compared with an appropriate control subgroup. Individual patient matching ensured equal age and follow-up between groups and that an appropriate control (who had not suffered a retinal detachment before the age at which their individually matched treatment patient underwent prophylactic treatment) was selected. Matching was blinded to outcome events. Individual patient matching protocols purposely weighted bias against the effectiveness of treatment. All treatment side effects are reported. MAIN OUTCOME MEASURES: Time to retinal detachment and side effects occurring after prophylactic treatment. RESULTS: The bilateral control group (n = 194) had a 7.4-fold increased risk of retinal detachment compared to the bilateral prophylaxis group (n = 229) (hazard ratio [HR], 7.40; 95% confidence interval [CI], 4.53-12.08; P<0.001); the matched bilateral control group (n = 165) had a 5.0-fold increased risk compared to the matched bilateral prophylaxis group (n = 165) (HR, 4.97; 95% CI, 2.82-8.78; P<0.001). The unilateral control group (n = 104) had a 10.3-fold increased risk of retinal detachment compared to the unilateral prophylaxis group (n = 64) (HR, 10.29; 95% CI, 4.96-21.36; P<0.001); the matched unilateral control group (n = 39) had a 8.4-fold increased risk compared to the matched unilateral prophylaxis group (n = 39) (HR, 8.36; 95% CI, 3.24-21.57; P<0.001). No significant long-term side effects occurred. CONCLUSIONS: In the largest global cohort of type 1 Stickler syndrome patients published, all analyses indicate that the Cambridge prophylactic cryotherapy protocol is safe and markedly reduces the risk of retinal detachment.