Dysplasia Of The Hip Research Articles

Developmental dysplasia of the hip caused by homozygous TRIM33 pathogenic variant affecting downstream BMP pathway

BackgroundDevelopmental dysplasia of the hip (DDH), formerly termed congenital dislocation of the hip, is the most common congenital disease of the musculoskeletal system in newborns. While familial predilection to DDH...

Review of susceptibility genes in developmental dysplasia of the hip: A comprehensive examination of candidate genes and pathways

AbstractDevelopmental dysplasia of the hip (DDH) is one of the most prevalent skeletal deformities, primarily due to the incompatibility between the acetabulum and femoral head. It includes complete dislocation, partial dislocation, instability with femoral head subluxation, and a range of imaging abnormalities that reflect inadequate acetabular formation. Known risk factors for DDH include positive family history, sex, premature birth, non‐cephalic delivery, oligohydramnios, gestational diabetes mellitus, maternal hypertension, associated anomalies, swaddling clothes, intrauterine space restriction, and post‐term pregnancy. Various research designs have been employed in DDH studies to identify relevant genes, including candidate gene association studies (CGAS), genome‐wide association studies (GWAS), restriction fragment length polymorphism (RFLP), and whole exome sequencing (WES). To date, multiple DDH‐associated genes have been identified in various populations. Despite extensive research into the epidemiology, risk factors, and genes associated with DDH, its pathogenesis remains unclear. This study provides a comprehensive summary of DDH research designs and evidence for relevant gene mutations through a PubMed search.

A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease

PurposeLegg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. This study aims to determine if previously validated pelvic obliquity radiographic parameters, used for assessing acetabular retroversion in developmental dysplasia of the hip, are applicable to patients with LCPD and its prognostic value.MethodA retrospective study of patients with Legg Calve Perthes disease was carried out, analysing 4 pelvic parameters: Ilioischial Angle, Obturator Index, Sharp’s Angle and Acetabular Depth-Width Ratio (ADR). The differences between healthy and affected hips were studied, and subsequently, it was assessed whether these parameters have prognostic value in the disease outcome.ResultsStatistically significant differences have been obtained in the ilioischial angle, obturator index and ADR, between the affected and healthy hip. However, only the Acetabular Depth-Width Ratio showed predictive value for the disease outcome.ConclusionAlthough this study revealed differences in pelvic parameters between healthy and diseased hips, with only the ADR showing statistical significance in the disease's evolution and prognosis, further studies with larger sample sizes are necessary.

Prognosticating Residual Dysplasia at Skeletal Maturity Following Closed Reduction for Developmental Dysplasia of the Hip: A Long-Term Study with an Average 20-Year Follow-up.

Patients with developmental dysplasia of the hip (DDH) are at risk for residual acetabular dysplasia even after successful closed reduction. The aim of this study was to identify predictors of long-term outcomes in order to guide prognostication and management. Patients who were treated for DDH at 2 institutions between 1970 and 2010 and had follow-up until skeletal maturity were screened for inclusion. Hips that underwent open reduction were excluded to reduce iatrogenic confounding. Syndromal (including neuromuscular and arthrogrypotic) hip instability with collagenopathies were excluded. Demographic characteristics, Tönnis grade, age at the time of the reduction, surgical treatment, acetabular index, lateral center-edge angle, residual dysplasia graded using the Severin classification, and the presence and type of proximal femoral growth disturbance categorized using the Bucholz and Ogden classification were assessed. In addition, the the acetabular angle was recorded at the latest follow-up before secondary procedures, and the Oxford Hip Score and 5-level EuroQoL (EQ)-5 Dimension score were recorded at the latest follow-up. To account for repeated measures, generalized estimating equations (GEE) logistic regression was utilized for the multivariable analysis. A support vector machine model and a receiver operating characteristic curve analysis were utilized to identify prognostication thresholds. One hundred and seven hips (96 female, 11 male) that were followed to skeletal maturity, with a mean follow-up of 20 years (range, 10 to 54 years), were included in the analysis. Eighty-nine hips (83%) demonstrated a good outcome at skeletal maturity, with a Severin grade of I or II. Major growth disturbances of Bucholz and Ogden types II, III, or IV were present in 13 hips (12%). At the latest follow-up after skeletal maturity (before any secondary procedures), the mean acetabular angle was 45° ± 4° and the mean lateral center-edge angle was 26° ± 8°. The mean Oxford Hip Score and EQ visual analog scale values were 47 and 86, respectively. A GEE logistic regression analysis of 1,135 observations revealed that the acetabular index (odds ratio [OR], 1.16 per degree; p < 0.001) and age (OR, 1.20 per year; p = 0.003) were significant predictors of a poor outcome (i.e., Severin grade III, IV, or V). Significant differences in acetabular indices across all age groups were found between hips with a good outcome and those with a poor outcome. Age-specific acetabular index prognostication cutoff values are presented. This long-term follow-up study demonstrated that the age-specific acetabular index remains an important predictor of residual dysplasia at skeletal maturity. The proposed prognostication chart and thresholds herein can help to guide orthopaedic surgeons and parents when contemplating the use of an intervention versus surveillance to optimize long-term outcomes. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Acetabular morphology variations in a Hispanic population.

Rotational abnormalities of the hip have been implicated in the etiology of diseases, such as hip dysplasia, osteoarthritis, and femoroacetabular impingement. Despite the extensive literature on hip morphology, there is a gap in knowledge regarding variations in the Hispanic population. To describe the bony anatomy variations of the acetabulum in a Hispanic population. This is a cross-sectional study. We studied 182 computed tomography (CT) images in patients aged older than 21 years, who had undergone pelvic CT for any condition, except hip fracture. Measurements of acetabular version, anterior and posterior acetabular sector angles (AASA/PASA) and horizontal acetabular sector angles (HASA) were made. Acetabular variations were then compared to weight and sex data. The mean acetabular anteversion was greater in women (P < 0.001). Women exhibited a greater PASA (P < 0.05); however, men had a greater AASA (P < 0.05). Underweight individuals had a smaller PASA (P < 0.01) and HASA (P < 0.05) than individuals with a normal weight. The Hispanic hip is morphologically similar to other populations previously reported in the literature; however, Hispanic men have less coverage of the femoral head by the posterior acetabular wall when compared to women of the same ethnicity. These abnormalities have a direct impact on management and surgical approach in patients treated for femoroacetabular impingement and hip dysplasia.

Gait pathology presented with developmental dysplasia of the hip: a control case study

A well-known and long-term complication of developmental dysplasia of the hip (DDH) is improper gait pattern, early regressive joint disorder, and permanent pain. It can affect the family's psychological, social, and functional parts. This study planned to resolve foot posture and gait analysis across patients with developmental hip dysplasia and correlate it with the control group. Case-control studies determine the main results. We correlated the gait analysis results on the Zebris FDM platform. The case included candidates with DDH under conservative treatment with an abduction brace and a control group with healthy participants. This study was conducted at King Abdullah Specialized Children Hospital, Riyadh, in the Kingdom of Saudi Arabia. This research enclosed 445 outcomes with DDH and 168 for the control category. The Sign test presented a significant diversity in Zebris FDM outcomes between DDH and the control group, especially in left foot external rotation with a p-value of 0.01 (left hip mean of 4.53, n=445, SD 8.78). A significant variation was present in step width, stance phase on both legs, single support, load response, swing phase, pre-swing, and a double support p-value of 0.00 (p&lt;0.05). W-sitting was preferred in 256 (n=445, 58%) of the DDH results and by 61 (n=168, 36%) from the control group. This study's outcomes presented a greater risk of pronation on the left foot and gait alteration on the right lower limb. The gait investigation presented a clear description of its patterns in paediatrics with DDH. Analyzing the gait among the DDH and the control group demonstrated a variation in each gait outcome from Zebris FDM platform software. DDH has a negative response on the gait pattern and foot posture, this is a great consequence presented in connection with Saudi applicants. Keywords: FDM, DDH, gait, control group, Kingdom of Saudi Arabia

Finite element analysis evaluation of hypothetical alternative treatment scenarios for neglected developmental dysplasia of the hip.

The study aimed to evaluate three different degrees of correction in the surgical treatment of neglected developmental dysplasia of the hip (DDH) using finite element models based on computed tomography. Three tridimensional FEA models of hypothetical post-operative (PO) outcomes were developed, based on three tridimensional CT of a pediatric patient diagnosed with luxated neglected DDH: One with the acetabular index of the contralateral hip (CLAT); another based on a theoretical Bombelli biomechanical model (BMB); and another recreating the patient's actual PO. The stresses in the affected hip were greater than those in the unaffected hip. CLAT showed the greatest stress and the smallest loading zone (LZ). In contrast, BMB showed the smallest stress and the biggest LZs. The approach based on the BMB gave the best results in terms of the distribution of the stresses over the hip, whereas the worst was CLAT. Qualitatively, estimating the stability and range of movement of the hip, the PO case was considered the best.

An automated framework for pediatric hip surveillance and severity assessment using radiographs.

Hip dysplasia is the second most common orthopedic condition in children with cerebral palsy (CP) and may result in disability and pain. The migration percentage (MP) is a widely used metric in hip surveillance, calculated based on an anterior-posterior pelvis radiograph. However, manual quantification of MP values using hip X-ray scans in current standard practice has challenges including being time-intensive, requiring expert knowledge, and not considering human bias. The purpose of this study is to develop a machine learning algorithm to automatically quantify MP values using a hip X-ray scan, and hence provide an assessment for severity, which then can be used for surveillance, treatment planning, and management. X-ray scans from 210 patients were curated, pre-processed, and manually annotated at our clinical center. Several machine learning models were trained using pre-trained weights from Inception ResNet-V2, VGG-16, and VGG-19, with different strategies (pre-processing, with and without region of interest (ROI) detection, with and without data augmentation) to find an optimal model for automatic hip landmarking. The predicted landmarks were then used by our geometric algorithm to quantify the MP value for the input hip X-ray scan. The pre-trained VGG-19 model, fine-tuned with additional custom layers, outputted the lowest mean squared error values for both train and test data, when ROI cropped images were used along with data augmentation for model training. The MP value calculated by the algorithm was compared to manual ground truth labels from our orthopedic fellows using the hip screen application for benchmarking. The results showed the feasibility of the machine learning model in automatic hip landmark detection for reliably quantifying MP value from hip X-ray scans. The algorithm could be used as an accurate and reliable tool in orthopedic care for diagnosing, severity assessment, and hence treatment and surgical planning for hip displacement.

Nociceptive threshold measurement as a non‐invasive functional test of an epidural injection in a dog

AbstractWe present a case of a 3‐year‐old, male Border Collie with severe hip dysplasia and osteoarthritis undergoing total hip replacement, notably having a history of a previous hip surgery with inadequate epidural analgesia. Our objective was to evaluate epidural efficacy before surgery using nociceptive threshold measurement. Nociceptive thresholds were measured with transdermal electrical stimulation via the Dolosys Pain Tracker device. The dog received epidural ropivacaine and morphine, resulting in a cessation of withdrawal response and electromyographic activity. This effect was confirmed under anaesthesia. Postoperatively, the dog recovered without relevant complications. In conclusion, nociceptive threshold measurement using the Dolosys Pain Tracker device allowed immediate confirmation of epidural efficacy, reducing the risk of intraoperative analgesic inadequacy. This approach may enhance surgical pain management in challenging cases.

The Role of Contrast-enhanced Ultrasound in the Femoral Head Perfusion Evaluation: A Pilot Study

ObjectivesWe explored the value of contrast-enhanced ultrasound (CEUS) in evaluating femoral head (FH) perfusion, guiding interventions and follow-up for infants with developmental dysplasia of the hip (DDH) and septic arthritis of the hip (SAH). The aim was to provide robust evidence for clinical assessment. MethodsTen infants, including 7 with DDH and 3 with SAH, were prospectively enrolled, with their bilateral hips alternately scanned during the CEUS exams. Twenty hips were classified into the case group (n = 11) and the control group (n = 9). Pre- and post-interventional studies were performed in DDH infants requiring interventions. FH perfusion was assessed by the perfusion area ratio (PAR) and quadrant location of microbubble-defect regions. ResultsIn the case group, 25 CEUS studies were conducted, including 11 baseline, 7 follow-up and 7 post-intervention studies. The PAR significantly decreased in the case group (49.79% vs. 100.00%, p < 0.05). The microbubble-defect regions averagely affected 2 quadrants, primarily quadrat No. 3 (30%) and No. 4 (32%). Seven hip abduction angle adjustments were made based on pre-interventional studies, resulting in a significant increase in PAR in post-interventional studies (37.63% vs. 60.24%, p < 0.05). PAR increased in follow-up studies compared to baseline values (45.61% vs. 76.07%, p < 0.05). The inter- and intra-observer reproducibility of PAR measurements were excellent (intraclass correlation coefficient, both 0.97). ConclusionCEUS proves to be a promising technique for quantitatively detecting FH perfusion in DDH and SAH infants with high reproducibility. It is valuable for baseline, intra-intervention and follow-up studies, aiming in clinical conditions and therapeutic effect evaluation.

Association of osteotomy, age, and component fixation with the outcomes of total hip arthroplasty in patients with hip dysplasia: a Dutch population-based registry study.

Hip dysplasia can present challenges for total hip arthroplasty (THA) due to anatomic abnormalities. We aimed to assess the association of age, sex, osteotomies prior to THA, and fixation method on 5- and 10-year revision-free implant survival and patient-reported outcome measures (PROMs) of THAs in patients with hip dysplasia. Using Dutch Arthroplasty Register data, we studied hip dysplasia patients receiving primary THAs in 2007-2021 (n = 7,465). THAs were categorized by age, pelvic osteotomy prior to THA (yes/no), and fixation (cemented, uncemented, hybrid, reverse hybrid). Kaplan-Meier and multivariable Cox models were used to determine 5- and 10-year revision-free implant survival and adjusted hazard ratios including 95% confidence intervals (CIs). Reasons for revision and PROMs were compared within the categories. We found a 10-year revision-free implant survival of 94.9% (CI 94.3-95.5). Patients younger than 50 years had a 10-year implant survival of 93.3% (CI 91.9-94.7), Patients with prior pelvic osteotomy had a 10-year implant survival of 92.0% (CI 89.8-94.2). Fixation method and sex were not associated with implant survival. Patients with a prior pelvic osteotomy had more revisions due to cup loosening and reported lower PROM scores than patients without earlier osteotomy. 5- and 10-year revision-free implant survival rates of THA for hip dysplasia are 96.4% and 94.9%. Age and prior osteotomies were associated with decreased implant survival rates in patients with hip dysplasia, while fixation method was not. Prior osteotomies were also associated with reduced PROM scores.

Association between ossific nucleus volume changes and postoperative avascular necrosis risk in children with developmental dysplasia of the hip

This study aimed to investigate the correlation between ossific nucleus volume and avascular necrosis (AVN) in pediatric patients diagnosed with developmental dysplasia of the hip (DDH). Analyzing 211 cases, including 119 open reduction (OR) and 92 closed reduction (CR) procedures, we quantified ossific nucleus volume using magnetic resonance imaging (MRI). Categorizing the OR group based on ossific nucleus volume revealed no statistically significant difference in AVN incidence. Similarly, in the CR cohort, there was no significant discrepancy in AVN occurrence between subgroups with or without the ossific nucleus. Logistic regression in CR identified the international hip dysplasia institute (IHDI) grade as a significant AVN risk factor (p = 0.007). IHDI grades 3 and 4 exhibited a 6.94 times higher likelihood of AVN compared to grades 1 and 2. Across CR and OR, neither initial age nor ossific nucleus volume emerged as AVN risk factors. In conclusion, ossific nucleus volume does not pose a risk for AVN in DDH children undergoing CR or OR, emphasizing the clinical significance of IHDI grading in predicting AVN risk during CR and the importance of early intervention to prevent treatment delays.

Advances in Ultrasound-Guided Surgery and Artificial Intelligence Applications in Musculoskeletal Diseases.

Ultrasound imaging is a vital imaging tool in musculoskeletal medicine, with the number of publications on ultrasound-guided surgery increasing in recent years, especially in minimally invasive procedures of sports, foot and ankle, and hand surgery. However, ultrasound imaging has drawbacks, such as operator dependency and image obscurity. Artificial intelligence (AI) and deep learning (DL), a subset of AI, can address these issues. AI/DL can enhance screening practices for hip dysplasia and osteochondritis dissecans (OCD) of the humeral capitellum, improve diagnostic accuracy for carpal tunnel syndrome (CTS), and provide physicians with better prognostic prediction tools for patients with knee osteoarthritis. Building on these advancements, DL methods, including segmentation, detection, and localization of target tissues and medical instruments, also have the potential to allow physicians and surgeons to perform ultrasound-guided procedures more accurately and efficiently. This review summarizes recent advances in ultrasound-guided procedures for musculoskeletal diseases and provides a comprehensive overview of the utilization of AI/DL in ultrasound for musculoskeletal medicine, particularly focusing on ultrasound-guided surgery.

Evaluation of the thickness of acetabular cartilage by ultrasound in developmental dysplasia of the hip.

It has been reported that the cartilaginous roof of the acetabulum is thicker in infants with developmental dysplasia of the hip (DDH) than in those with healthy hips. However, there is limited research on the changes in the thickness of acetabular cartilage after follow-up or treatment of DDH. This study aims to report the thickness of acetabular cartilage before and after treatment of DDH. In this prospective study, infants with clinical suspicion of DDH were enrolled in the pediatric outpatient service in our hospital from January 2022 to August 2023. The thickness of acetabular cartilage was measured in the standard coronal plane. Borderline hips (Graf IIa type) were monitored with monthly ultrasound examination until they were classified as normal hips (Graf I type), while dysplastic hips (Graf IIb type or worse) were treated with the Pavlik harness until they were also classified as normal hips in the final ultrasound examination. A total of 592 children [median age, 96 days (interquartile range, 70-142 days); 197 boys] were enrolled in the study. The thickness of acetabular cartilage in dysplastic hips (4.3 ± 1.6 mm) was greater than that in normal hips (3.0 ± .39 mm, P < 0.001) and borderline hips (3.1 ± .57 mm, P < 0.001). In borderline hips, the thickness of acetabular cartilage decreased from 3.1 ± .57 mm in the initial evaluation to 2.9 ± .53 mm in the final follow-up scan (P = 0.01). In dysplastic hips, the thickness of acetabular cartilage decreased from 4.3 ± 1.6 mm in the initial evaluation to 3.5 ± .51 mm after treatment (P = 0.003). The thickness of acetabular cartilage in dysplastic hips after treatment remained greater than that in normal hips (P < 0.0001). The thickness of acetabular cartilage decreased after follow-up or treatment of DDH. Further research is required to determine whether cartilage that remain thicker in dysplastic hips than that in normal hips after treatment should be considered an early indicator of residual acetabular dysplasia.

Integration of 3D printing and case-based learning in clinical practice for the treatment of developmental dysplasia of the hip

BackgroundCase-based learning (CBL) utilizing three-dimensional (3D) printed hip joint models is a problem-solving teaching method that combines the tactile and visual advantages of 3D-printed models with CBL. This study aims to investigate the impact of integrating 3D printing with CBL on learning developmental dysplasia of the hip (DDH).MethodsWe conducted a prospective study from 2022 to 2023, including 120 fourth-year clinical medical students at Xuzhou Medical University. Students were randomly allocated into two groups of 60 participants each. The CBL group received conventional CBL teaching methods, while the 3D + CBL group utilized 3D-printed models in conjunction with CBL. Post-teaching, we analyzed and compared the theoretical and practical achievements of both groups. A questionnaire was designed to assess the impact of the educational approach on orthopedic surgery learning.ResultsThe theory scores of the CBL group (62.88 ± 7.98) and 3D + CBL group (66.35 ± 8.85) were significantly different (t = 2.254, P = 0.026); the practical skills scores of the CBL group (57.40 ± 8.80) and 3D + CBL group (63.42 ± 11.14) were significantly different (t = 3.283, P = 0.001). The questionnaire results showed that the 3D + CBL group was greater than the CBL group in terms of hip fundamentals, ability to diagnose cases and plan treatments, interesting teaching content, willingness to communicate with the instructor and satisfaction.ConclusionsThe integration of 3D printing with case-based learning has yielded positive outcomes in teaching DDH, providing valuable insights into the use of 3D-printed orthopedic models in clinical education.

A retrospective study of arthroscopic treatment for patients with bordline developmental dysplasia of the hip.

Hip arthroscopy is effective in treating bordline developmental dysplasia of the hip (BDDH), but there are only a few clinical reports in China, and its postoperative failure rate is still a problem that cannot be ignored. The aim of this study was to analyze the clinical effect of hip arthroscopy in BDDH treatment in China and to explore the risk factors influencing the efficacy of hip arthroscopy in BDDH treatment. All of 22 cases of BDDH treated with arthroscopy in our hospital from November March 2017 to February 2022 were analyzed retrospectively, including ten males and 12 females, with an average age of 34.7 ± 9.5 years (19-53 years). All patients underwent arthroscopic treatment with acetabular plasty, labral repair, femoral osteoplasty, and capsular plication. Visual Analogue Scale (VAS), modified Harris Hip Scores (mHHS), Hip Outcome Score-activities of Daily Living (HOS-ADL) and International Hip Outcome Tool-12 (iHOT-12) were measured before operation and at the follow-up, and statistical analysis was performed. The Minimum clinically significant difference (MCID) and Patient Acceptable Symptom State (PASS) were also obtained. 22 patients were followed up, and the follow-up time was ≥ one year, with an average of 21.4 ± 8.2 months. The VAS score decreased from 5.27 ± 1.58 points before surgery to 1.96 ± 0.92 points at the follow-up, and the difference was statistically significant (t = 9.05,P < 0.001). The mHHS score increased from 64.84 ± 13.58 points before surgery to 90.4 ± 10.11 points at the follow-up, and the difference was statistically significant (t=-7.07, P < 0.001). The HOS-ADL score increased from 68.92 ± 11.76 points before surgery to 88.91 ± 9.51 points at the follow-up, and the difference was statistically significant (t=-8.15,P < 0.001). The iHOT-12 score increased from 49.32 ± 12.01 points before surgery to 79.61 ± 15.89 points at the follow-up, and the difference was statistically significant (t=-7.66,P < 0.001). The MCID (mHHS) and MCID (HOS-ADL) were 81.8% and 77.3% respectively, and the PASS (mHHS) and PASS (HOS-ADL) were 86.4% and 72.7% respectively at the follow-up. Hip arthroscopy can achieve good short-term outcomes in the treatment of BDDH. IV Therapeutic Study.

Comparison of Cranial Cruciate Ligament Rupture Incidence among Parous and Nulliparous Rottweiler Bitches: Evidence from a Lifetime Cohort Study Supporting a Paradigm of Pregnancy-Associated Protection against Subsequent Non-Reproductive Disease Outcomes.

Emerging evidence in women supports the notion that pregnancy may reset disease resistance, thereby providing protection against subsequent adverse health outcomes, but this hypothesis has not been adequately explored in domestic dogs. Cranial cruciate ligament (CCL) rupture is a degenerative orthopedic disease that frequently affects pet dogs, and its risk has been associated with disruption of the reproductive hormone axis. Our research team is conducting a lifetime cohort study of purebred Rottweilers in North America that have lived 30% longer than breed-average. Detailed medical and reproductive histories of 33 nulliparous and 32 parous Rottweilers were generated from questionnaires and review of medical records. Interviews with owners of bitches in the nulliparous group served to limit selection bias, confirming that in no instance was the reason for nulliparity based upon the owner's suspicion that a bitch had a heightened risk for CCL rupture. The risk of CCL rupture associated with parity and other exposure variables was estimated using multivariate logistic regression. Overall, CCL rupture was diagnosed in 17 of 65 (26%) bitches. Median age at first litter and CCL rupture were 3.6 and 6.5 years, respectively. Compared to nulliparous, parous bitches had a significant 94% reduction in CCL rupture risk adjusted for duration of ovary exposure, overweight body condition, dietary pattern, habitual physical activity, and work/sport activity [ORadjusted (95% CI) = 0.06 (0.01-0.46); (p = 0.006)]. The observed parity-associated CCL rupture risk reduction remained robust in sensitivity analysis excluding six nulliparous bitches for which decision not to breed was based on diagnosis of hip or elbow dysplasia, conditions which may be genetically linked to CCL rupture [ORadjusted (95% CI) = 0.08 (0.01-0.58); (p = 0.01)]. This work sets the stage for replication studies in other canine populations that should begin to explore the mechanistic basis for parity-associated CCL rupture risk reduction and to pursue other non-reproductive health outcomes in bitches whose incidence or severity may be parity-sensitive.

Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype

BackgroundChromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty.ResultsWe identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene.ConclusionThis report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

Rates and risk factors for failure of reduction in closed reduction in developmental dysplasia of the hip: a systematic review and meta-analysis.

In developmental dysplasia of the hip (DDH), concentric reduction of dislocated hips cannot be achieved by closed reduction in many cases, and open reduction is required ('failure of reduction'). The incidence of cases requiring open reduction and the significance of risk factors for unsuccessful reduction remain unclear. We investigated the overall rate and the risk factors for failed closed reduction in DDH. We followed the Cochrane recommendations in our systematic review and meta-analysis. We performed a systematic search in three medical databases to identify all studies reporting on pediatric patients with hip dislocation in DDH on 2 July 2022. Eligible studies reported on the rate of failure in children younger than 36 months. We calculated odds ratios (ORs) with 95% CIs from two-by-two tables (event rate in risk group, event rate in non-risk group). We identified 13 316 studies and included 62 studies (5281 hips) for failure rate and 34 studies (3810 hips) for risk factor analysis. The overall rate of failure in closed reduction was 20%. The risk of failure of reduction increased with the grade of dislocation and was significantly higher for high dislocations (group 0-24: IHDI 4 vs IHDI 2 OR: 17.45, CI: 9.26-32.92; Tönnis 4 vs Tönnis 2 OR: 14.67, CI: 1.21-177.37; Graf IV vs Graf III OR: 3.4, CI: 2.27-5.09). Male gender was also a significant risk factor (OR: 2.27, CI: 1.13-4.56) in group 0-36. Higher grade dislocations and male gender are significant risk factors for failure of reduction in closed reduction in hip dislocation in DDH.

The markers of the predictive DNA test for canine hip dysplasia may have a stronger relationship with elbow dysplasia

Canine hip and elbow dysplasias, which are prevalent orthopedic conditions rooted in developmental and hereditary factors are yet to be comprehensively assessed. This study aimed to address this gap by exploring the prognostic significance of five markers linked to canine hip dysplasia using available genome-wide association studies (GWAS) data. The influence of these markers on both hip and elbow dysplasia was examined in dogs exposed to standardized environmental conditions. We made a groundbreaking discovery using custom primers, qPCR assays, and evaluation of fluorescent resonance energy transfer (FRET) probes. Three specific SNPs previously associated with the risk of canine hip dysplasia demonstrated a potentially stronger correlation with elbow dysplasia. Notably, the SNP at nucleotide position 22691322, located near the canine CHST3 gene, displayed significance as a marker in multivariable logistic regression analysis. Surprisingly, none of the initially targeted SNPs showed a direct association with hip dysplasia. The genomic positions of these SNPs reside within a region conserved across mammals. In silico analyses suggested that the relevant variant might be positioned in a region linked to bone and muscle structures. Our findings revealed a remarkable relationship between SNP2 genotypes and methylation patterns, shedding light on the underlying mechanism that partially explains the genotype-phenotype correlation in canine CHST3. These groundbreaking findings offer essential insights for future, more extensive investigations into canine orthopedic health. This research significantly contributes to our understanding of the molecular foundations of hip and elbow dysplasia in dogs by charting a course for advancements in veterinary medicine and the overall well-being of canine companions.