scholarly journals Epidemiology and Phenotypic Characteristics of Dual Molecular Diagnosis Cases in Skeletal Abnormality

2021 ◽  
Author(s):  
Lian Liu ◽  
Liying Sun ◽  
Yujun Chen ◽  
Chenxi Yu ◽  
Yingzhao Huang ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Marfan Syndrome ◽  
Molecular Diagnosis ◽  
Dual Diagnosis ◽  
Early Onset ◽  
Early Onset Scoliosis ◽  
Type I ◽  
Skeletal Abnormality ◽  
Phenotypic Characteristics ◽  
Skeletal Abnormalities

Abstract Background Skeletal abnormality is a heterogeneous group of disorders that affects the composition and structure of bone and cartilage. In our previous studies, we have revealed that a substantial proportion of cases with early-onset scoliosis could be explained by monogenic disorders such as Marfan syndrome and Ehlers-Danlos syndrome. More recently complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal abnormalities. To explore the molecular epidemiology and phenotypic characteristics of dual diagnosis in skeletal abnormalities, we described cases with dual molecular diagnosis from the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study.Results In total, 1108 patients with skeletal abnormality from the DISCO study underwent Exome Sequencing. We identified eight probands with dual molecular diagnosis, including three (0.7%) from individuals with early-onset scoliosis (EOS), three (0.5%) from individuals with short stature, and two (2%) from individuals with congenital hand/foot deformity (CHFA). Other skeletal abnormalities observed in these individuals included bone fracture and interphalangeal joint contracture. All the eight probands have dual diagnosis of two autosomal dominant (AD) diseases. A total of 16 variants in 12 genes were identified. A substantial rate (5 of 10) of the identified causal variants were of de novo origin. The frequently observed molecular diagnoses (observed in more than one patient) include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700). These patients with dual molecular diagnosis often present blended phenotypes of two diseases, which significantly complicate their diagnostic process. Conclusions This study revealed the molecular epidemiology and complex diagnostic odyssey of dual molecular diagnosis through analyzing the clinical traits of skeletal abnormalities in eight patients.

Growth-friendly Instrumentation for the Treatment of Early-onset Scoliosis in Marfan Syndrome

2019 ◽  
Vol 7 (6) ◽  
pp. 1027-1028
Author(s):  
Laura Bellaire ◽  
Graham Fedorak ◽  
John Heflin ◽  
Joshua Klatt ◽  
John Smith ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Early Onset ◽  
Early Onset Scoliosis

scholarly journals Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS)

2020 ◽  
Vol 58 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Sen Zhao ◽  
Yuanqiang Zhang ◽  
Weisheng Chen ◽  
Weiyu Li ◽  
Shengru Wang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Early Onset ◽  
Diagnostic Yield ◽  
Early Onset Scoliosis ◽  
Chinese Patients ◽  
Molecular Diagnostic ◽  
Organ Systems ◽  
The Us ◽  
The Usa

BackgroundEarly-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening.MethodsIn this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited.ResultsAfter ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis.ConclusionES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

scholarly journals Early-Onset Osteoporosis

2021 ◽  
Author(s):  
Outi Mäkitie ◽  
M. Carola Zillikens
Keyword(s):  
Young Adults ◽  
Early Onset ◽  
Type I Collagen ◽  
Young Patients ◽  
Fragility Fractures ◽  
Underlying Disease ◽  
Bone Fragility ◽  
Sphingolipid Metabolism ◽  
Type I ◽  
Loss Of Function

AbstractOsteoporosis is a skeletal disorder with enhanced bone fragility, usually affecting the elderly. It is very rare in children and young adults and the definition is not only based on a low BMD (a Z-score < − 2.0 in growing children and a Z-score ≤ − 2.0 or a T-score ≤ − 2.5 in young adults) but also on the occurrence of fragility fractures and/or the existence of underlying chronic diseases or secondary factors such as use of glucocorticoids. In the absence of a known chronic disease, fragility fractures and low BMD should prompt extensive screening for secondary causes, which can be found in up to 90% of cases. When fragility fractures occur in childhood or young adulthood without an evident secondary cause, investigations should explore the possibility of an underlying monogenetic bone disease, where bone fragility is caused by a single variant in a gene that has a major role in the skeleton. Several monogenic forms relate to type I collagen, but other forms also exist. Loss-of-function variants in LRP5 and WNT1 may lead to early-onset osteoporosis. The X-chromosomal osteoporosis caused by PLS3 gene mutations affects especially males. Another recently discovered form relates to disturbed sphingolipid metabolism due to SGMS2 mutations, underscoring the complexity of molecular pathology in monogenic early-onset osteoporosis. Management of young patients consists of treatment of secondary factors, optimizing lifestyle factors including calcium and vitamin D and physical exercise. Treatment with bone-active medication should be discussed on a personalized basis, considering the severity of osteoporosis and underlying disease versus the absence of evidence on anti-fracture efficacy and potential harmful effects in pregnancy.

scholarly journals Analysis of serum levels of titanium and aluminium ions in patients with early onset scoliosis operated upon using the magnetic growing rod—a single centre study of 14 patients

2021 ◽  
Author(s):  
Mandar Deepak Borde ◽  
Sarang Sapare ◽  
Emile Schutgens ◽  
Chadi Ali ◽  
Hilali Noordeen
Keyword(s):  
Early Onset ◽  
Serum Levels ◽  
Early Onset Scoliosis ◽  
Ion Concentration ◽  
Long Term Effects ◽  
Blood Concentrations ◽  
Growing Rod ◽  
Rod System ◽  
Rod Breakage

Abstract Study design A cross-sectional retrospective Level 3 study. Objective To study the serum levels of Titanium and Aluminium ions in patients operated using the magnetically controlled growing rod (MCGR) system. Summary of background data 14 consecutive patients of early onset scoliosis with varying etiology managed with MCGR system with a minimum follow-up of 24 months were selected for the study. The group consisted of two boys (14.3%) and 12 girls (85.7%). The average age of the patients at the time of surgery was 10.4 years (5–15 years). The average period of follow-up was 43.7 months (28–79 months). After informed consent of the subjects and their caretakers, serum levels of titanium and aluminium were measured. These levels were then assessed with regards to the number of screws used, number of distractions and complications. Methods The concentration of titanium and aluminium ions in the serum was measured using high resolution inductively coupled plasma mass spectrometry. Results For the sake of ease of assessment, patients were divided into three etiology-based groups—idiopathic (n = 6), neuromuscular (n = 2) and syndromic (n = 6). The mean serum titanium level was 15.9 μg/L (5.1–28.2 μg/L) while that of aluminium was 0.1 μmol/L (0.1–0.2 μmol/L). Of the 14 patients, 2 (14.2%) patients had mechanical failure (actuator pin dysfunction), 3 (21.4%) had rod breakage requiring revision surgery and one patient (7.1%) had surgical site infection managed with appropriate antibiotics. Patients undergoing revision for rod breakage did not show any metallosis of the tissues during surgery. Conclusion Analysis of patients with scoliosis operated using the magnetic growing rod system concludes that it is accompanied by presence of titanium in the blood but whether clinically significant or not needs to be ascertained by comparison of preoperative and postoperative blood concentrations of the titanium ions in individual subjects. The aluminium ion concentration remains within normal limits. Though implant malfunction may raise the titanium levels in the blood, its clinical significance needs to be determined. The aluminium levels are not affected irrespective to the presence or absence of complications. The long-term effects of raised titanium levels in the blood also warrant further prospective studies designed for precise and deeper analyses.

Reproducibility of the classification of early onset scoliosis (C-EOS)

2020 ◽  
Vol 8 (2) ◽  
pp. 285-293
Author(s):  
Casper Dragsted ◽  
Søren Ohrt-Nissen ◽  
Dennis Winge Hallager ◽  
Niklas Tøndevold ◽  
Thomas Andersen ◽  
...  
Keyword(s):  
Early Onset ◽  
Early Onset Scoliosis

scholarly journals Survey to describe variability in early onset scoliosis cast practices

2018 ◽  
Vol 12 (4) ◽  
pp. 406-412 ◽  
Author(s):  
A. Grzywna ◽  
A. McClung ◽  
J. Sanders ◽  
P. Sturm ◽  
L. Karlin ◽  
...  
Keyword(s):  
Early Onset ◽  
Congenital Scoliosis ◽  
Patient Characteristics ◽  
Study Groups ◽  
Early Onset Scoliosis ◽  
Radiographic Evaluation ◽  
Level Of Evidence ◽  
Major Curve ◽  
Radiographic Measurements ◽  
Multicentre Research

Purpose To investigate paediatric orthopaedists’ cast practices for early onset scoliosis regarding patient selection, cast application, radiographic evaluation, treatment cessation and adjunctive bracing. Methods A casting survey was distributed to all paediatric orthopaedists in Children’s Spine and Growing Spine Study Groups (n = 92). Questions included physician and patient characteristics, technique, treatment, outcomes, radiographic measurements and comparison to other treatments. A total of 55 orthopaedists (60%) responded, and descriptive statistics were calculated on the subset who cast (n = 45). Results A majority of respondents use cast treatment for idiopathic and syndromic scoliosis patients, but not for neuromuscular or congenital scoliosis patients. Major curve angle ranked most important in orthopaedists’ decision to commence cast treatment, in comparison with rib-vertebra angle difference or clinical observations. The major curve angle threshold to initiate casting was a median of 30° (20° to 70°), and the minimum patient age was median ten months (3 to 24). First in-cast and out-of-cast radiographs are taken standing, supine, awake, under anesthesia and/or in traction. In all, 58% consistently cast over or under the arm, while 44% vary position by patient. Respondents were divided about the use of a brace after cast treatment: 22% do not prescribe a brace, 31% always do and 36% do in some patients. Conclusions Future multicentre research studies must standardize radiographic practices and consider age and major curve angle at cast initiation and termination, scoliosis aetiology, shoulder position and treatment duration. Practices need to be aligned or compared in these areas in order to distinguish what makes for the best cast treatment possible. Level of Evidence V, Expert opinion

Retrieval and clinical analysis of distraction-based dual growing rod constructs for early-onset scoliosis

2017 ◽  
Vol 17 (10) ◽  
pp. 1506-1518 ◽  
Author(s):  
Genevieve Hill ◽  
Srinidhi Nagaraja ◽  
Behrooz A. Akbarnia ◽  
Jeff Pawelek ◽  
Paul Sponseller ◽  
...  
Keyword(s):  
Early Onset ◽  
Clinical Analysis ◽  
Early Onset Scoliosis ◽  
Growing Rod

scholarly journals Evaluation of changes in shoulder balance and prediction of final shoulder imbalance during growing-rod treatment for early-onset scoliosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ziyang Liu ◽  
Tie Liu ◽  
Yong Hai ◽  
Lingyun Wu ◽  
Junrui Jonathan Hai ◽  
...  
Keyword(s):  
Early Onset ◽  
Demographic Data ◽  
Potential Effect ◽  
Early Onset Scoliosis ◽  
Shoulder Balance ◽  
Related Factors ◽  
Growing Rod ◽  
Shoulder Imbalance ◽  
Entire Treatment

Abstract Background Obtaining and maintaining final shoulder balance after the entire treatment course is essential for early-onset scoliosis (EOS) patients. The relatively small number of growing-rod (GR) graduates who complete final fusion has resulted in an overall paucity of research on the GR treatment of EOS and a lack of research on the shoulder balance of EOS patients during GR treatment. Methods Twenty-four consecutive patients who underwent GR treatment until final fusion were included. Radiographic shoulder balance parameters, including the radiographic shoulder height (RSH), clavicle angle (CA), and T1 tilt angle (T1T), before and after each step of the entire treatment were measured. Shoulder balance changes from GR implantation to the last follow-up after final fusion were depicted and analysed. Demographic data, surgical-related factors, and radiographic parameters were analysed to identify risk factors for final shoulder imbalance. The shoulder balance of patients at different time points was further analysed to explore the potential effect of the series of GR treatment steps on shoulder balance. Results The RSH showed substantial improvement after GR implantation (P = 0.036), during the follow-up period after final fusion (P = 0.021) and throughout the entire treatment (P = 0.011). The trend of change in the CA was similar to that of the RSH, and the T1T improved immediately after GR implantation (P = 0.037). Further analysis indicated that patients with shoulder imbalance before final fusion showed significantly improved shoulder balance after fusion (P = 0.045), and their RSH values at early postfusion and the final follow-up did not show statistically significant differences from those in the prefusion shoulder balance group (P > 0.05). Early postfusion shoulder imbalance (odds ratio (OR): 19.500; 95% confidence interval (CI) = 1.777–213.949; P = 0.015) was identified as an independent risk factor for final shoulder imbalance. Conclusions Shoulder balance could be improved by GR implantation but often changes during the multistep lengthening process, and the final result is relatively unpredictable. Final fusion could further adjust the prefusion shoulder imbalance. Focusing on the prefusion shoulder balance of GR graduates and providing patients with early shoulder balance after fusion might be necessary.

Paper #11: Effectiveness of Serial Derotational Casting for Treatment of Children With Early-Onset Scoliosis

2014 ◽  
Vol 2 (6) ◽  
pp. 502-503
Author(s):  
Anny Hsu ◽  
Hiroko Matsumoto ◽  
Mark Sullivan ◽  
Evan Trupia ◽  
Benjamin Roye ◽  
...  
Keyword(s):  
Early Onset ◽  
Early Onset Scoliosis
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