Impact of pathogenic FBN1 variant types on the development of severe scoliosis in patients with Marfan syndrome

BackgroundAmong the several musculoskeletal manifestations in patients with Marfan syndrome, spinal deformity causes pain and respiratory impairment and is a great hindrance to patients’ daily activities. The present study elucidates the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome.MethodsWe retrospectively evaluated 278 patients with pathogenic or likely pathogenic FBN1 variants. The patients were divided into those with (n=57) or without (n=221) severe scoliosis. Severe scoliosis was defined as (1) patients undergoing surgery before 50 years of age or (2) patients with a Cobb angle exceeding 50° before 50 years of age. The variants were classified as protein-truncating variants (PTVs), which included variants creating premature termination codons and inframe exon-skipping, or non-PTVs, based on their location and predicted amino acid alterations, and the effect of the FBN1 genotype on the development of severe scoliosis was examined. The impact of location of FBN1 variants on the development of severe scoliosis was also investigated.ResultsUnivariate and multivariate analyses revealed that female sex, PTVs of FBN1 and variants in the neonatal region (exons 25–33) were all independent significant predictive factors for the development of severe scoliosis. Furthermore, these factors were identified as predictors of progression of existing scoliosis into severe state.ConclusionsWe elucidated the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. Patients harbouring pathogenic FBN1 variants with these genetic risk factors should be monitored carefully for scoliosis progression.

THE USE OF CRANIAL HALO TRACTION VERSUS TEMPORARY INTERNAL DISTRACTION IN STAGED SURGERY FOR SEVERE SCOLIOSIS: A COMPARATIVE STUDY

ABSTRACT Objective: To determine which method is more effective – cranial halo traction or temporary internal distraction – in staged surgeries for patients with severe (≥ 100°) and stiff (<25% flexibility) scoliosis. Methods: A sample of 12 patients with traction and 7 patients without traction, operated on between January 2013 and December 2017. The patients’ demographic data, the type of surgery performed, complications, and coronal and sagittal alignment parameters were recorded before surgery and in the final follow-up. The data were processed in SPSS 20.0. Comparisons were made between the means (Student's t-test) and the clinical and procedure-related characteristics (likelihood ratio and Fisher's Exact tests), at a confidence level of 0.05. Results: There were no significant intergroup differences for clinical characteristics, complications or degree of correction. However, more patients in the group submitted to temporary internal distraction required vertebral resection osteotomies during definitive surgery (p<0.05). Conclusions: Based on the results, it was not possible to establish which is the most effective method, but it is suggested that staged traction may be more effective, and safer, particularly when the surgeon is less experienced, during surgery on patients with severe and stiff scoliosis. Level of evidence IV; Vase series.

Does Preoperative Halo-Gravity Traction Reduce the Degree of Deformity and Improve Pulmonary Function in Severe Scoliosis Patients With Pulmonary Insufficiency? A Systematic Review and Meta-Analysis

Background: Halo-gravity traction is a commonly used clinical intervention to reduce surgical risk in patients with scoliosis before surgical correction. Some previous studies have focused on the application of halo-gravity traction on patients with severe spinal deformity and pulmonary insufficiency, but the overall effect of halo-gravity traction has not been fully understood. The object of the present study was to perform a meta-analysis exploring the efficacy of preoperative halo-gravity traction on radiographic measurement and pulmonary function in severe scoliosis patients with pulmonary insufficiency.Methods: We searched the medical works of literature completed before January 17, 2021, in the databases of Pubmed, Embase, and Cochrane Library. Studies that quantitatively analyzed the effects of halo-gravity traction on the deformity and pulmonary functions of patients with severe scoliosis were included. Two researchers independently conducted the literature search, data extraction, and quality assessment. We used the Review Manager Software (version 5.4) for statistical analysis and data analysis. Mean difference (MD) with 95% confidence intervals (CIs) were calculated to evaluate the effects of halo-gravity traction.Results: Seven studies involving 189 patients received halo-gravity traction therapy preoperatively were analyzed in our study. Preoperative halo-gravity traction significantly ameliorated the degree of deformity in severe scoliosis patients with pulmonary insufficiency, especially reduced coronal Cobb angle and sagittal Cobb angle effectively [mean deviation (MD) = 2 7.28 (95%CI 21.16–33.4), p &lt; 0.001; MD = 22.02 (95%CI 16.8–27.23), p &lt; 0.001]. Preoperative halo-gravity traction also improved the pulmonary functions in patients, especially increasing %FVC and %FEV1 [MD = −0.0662 (95%CI −0.0672–−0.0652), p &lt; 0.001; MD = −0.0824 (95%CI −0.0832–−0.081), p &lt; 0.001].Conclusions: Preoperative halo-gravity traction for severe scoliosis patients shows significant improvement in the degree of deformity and pulmonary functions. Halo-gravity traction is an effective method to improve the tolerance of patients to surgery in the perioperative period.

Relationship between BMP2/9 Levels and Spinal Function and Quality of Life in Patients with Severe Scoliosis after PVCR

Objective. To explore the relationship between (bone fusion associated protein) bone morphogenetic protein (BMP)2 and BMP9 and spinal function and quality of life in patients with severe scoliosis after posterior vertebral column resection (PVCR). Methods. 78 cases of severe scoliosis treated with PVCR surgery in our hospital from January 2015 to April 2018 were selected and set as the observation group, and 80 health examiners in the same period were selected and set as the control group. The ELISA method was used to detect the levels of BMP2 and BMP9 in the two groups. Also, the relationship between the recovery of spinal function, quality of life, and serum BMP2 and BMP9 in the observation group was analyzed. The receiver operating characteristic curve was used to evaluate the predictive value of BMP2 and BMP9 for complications after PVCR. Results. One month after PVCR, the serum BMP2 and BMP9 levels of patients with severe scoliosis were higher than those of healthy people P < 0.05 . One year after PVCR, Pearson correlation analysis showed that serum levels of BMP2 and BMP9 in patients with scoliosis were positively correlated with ODI scores (r = 0.778, P < 0.001 ; r = 0.746, P < 0.001 ), SRS-22 scores (r = 0.758, P < 0.001 ; r = 0.722, P < 0.001 ), and Cobb angle correction rate (r = 0.838, P < 0.001 ; r = 0.802, P < 0.001 ). Conclusion. The levels of BMP2 and BMP9 of patients with scoliosis after PVCR are higher than those of healthy people. After 1-year follow-up, the patients’ serum BMP2 and BMP9 levels were positively correlated with spinal function recovery, quality of life, and surgical efficacy. Among them, BMP2 and BMP9 had the highest correlation with PVCR surgical efficacy. Paying attention to the serum BMP2 and BMP9 levels of patients with scoliosis has certain clinical significance.

Anesthetic Management of a Rett Syndrome Patient at High Risk for Respiratory Complications

Rett syndrome (RTT) is a rare genetic disorder that can present challenges in airway management during general anesthesia. This is a case report involving a 23-year-old woman with RTT who received an intubated general anesthetic 3 times for dental treatment. The patient also had severe scoliosis, was bedridden, and had dysphagia. These contributing factors likely led to the development of postoperative respiratory complications including pneumonia after the first case. As a result, several changes were incorporated into the 2 subsequent anesthetic plans in efforts to reduce the risk of such complications. Despite these measures, the patient was suspected of having bronchitis postoperatively after the second anesthetic, although the third occurred uneventfully. Anesthetic management alterations included use of desflurane for anesthetic maintenance and postoperatively delaying oral intake and instituting active postural changes.

Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod

Urp1 and Urp2 are two neuropeptides of the urotensin II family identified in teleost fish and mainly expressed in cerebrospinal fluid (CSF)-contacting neurons. It has been recently proposed that Urp1 and Urp2 are required for correct axis formation and maintenance. Their action is thought to be mediated by the receptor Uts2r3, which is specifically expressed in dorsal somites. In support of this view, it has been demonstrated that the loss of uts2r3 results in severe scoliosis in adult zebrafish. In the present study, we report for the first time the occurrence of urp2, but not of urp1 , in two tetrapod species of the Xenopus genus. In X. laevis , we show that urp2 mRNA-containing cells are CSF-contacting neurons. Furthermore, we identified utr4, the X. laevis counterparts of zebrafish uts2r3, and we demonstrate that, as in zebrafish, it is expressed in the dorsal somatic musculature. Finally, we reveal that, in X. laevis, the disruption of utr4 results in an abnormal curvature of the antero-posterior axis of the tadpoles. Taken together, our results suggest that the role of the Utr4 signalling pathway in the control of body straightness is an ancestral feature of bony vertebrates and not just a peculiarity of ray-finned fishes.

Prevalence of Scoliosis in Hypermobile Ehlers-Danlos Syndrome

Objective: The main purpose of this study was to evaluate the prevalence, form, and severity of scoliosis in a population of adults meeting the 2017 criteria for hypermobile Ehlers-Danlos syndrome (hEDS). The second objective was to compare the prevalence of scoliosis versus other criteria at initial hEDS diagnosis. Methods: A retrospective study looking at the frequency and severity of scoliosis in adults (N=28) meeting the 2017 diagnostic criteria for hEDS through analysis of a full spine EOS® X-ray (EOS imaging, Paris, France) performed at the initial diagnosis. Severity was defined by the Cobb angle. Results: At the initial diagnosis, the mean age was 30.1 years (standard deviation [SD]: ±10.18 years). Twenty-nine percent (n=8/28) of patients fulfilling hEDS criteria presented with scoliosis. Thirty-two percent (n=9/28) of patients had scoliotic inflection and 39% (n=11/28) had no scoliosis. Scoliosis was mild-to-moderate with a mean Cobb angle of 13.6° (SD: ±3.5°). None of the patients had severe scoliosis requiring surgery. Compared to the 2017 diagnostic criteria, it is noteworthy that scoliosis prevalence in this present study population ranks at the level of the most frequent ones. Conclusion: This study provides interesting information regarding frequency of scoliosis and scoliotic inflection in a group of patients with hEDS. Although the patients did not present with severe forms of scoliosis at initial diagnosis, the results highlight the importance of systematically looking for scoliosis in adult and young patients, in order to follow progression and ensure appropriate management.