Skeletal Anomalies Research Articles

Botulinum toxin type A outcomes in infants with refractory congenital muscular torticollis.

The aim of this study was to determine the effectiveness of botulinum toxin type A (BoNT-A) injections in infants with congenital muscular torticollis (CMT) who were refractory to conservative management. This was a retrospective study in which all subjects included were seen between 2004 and 2013 and were deemed appropriate for BoNT-A injections. A total of 291 patients were reviewed for inclusion in the study, and 134 patients met the inclusion criteria. Each child was injected with 15-30 units of BoNT-A into each of the following muscles: ipsilateral sternocleidomastoid, upper trapezius, and scalene muscles. The key outcome and variable measurements analyzed included age at time of diagnosis, age at time of initiation of physical therapy, age at time of injection, total number of injection series utilized, muscles injected, and degrees of active and passive cervical rotation and lateral flexion pre- and post-injection. A successful outcome was documented if a child could achieve 45° of active lateral flexion and 80° of active cervical rotation post-injection. Secondary variables including sex, age at time of injection, number of injection series utilized, surgery required, adverse effects of botulinum toxin, presence of plagiocephaly, side of torticollis, orthosis used, presence of hip dysplasia, skeletal anomalies, complications during pregnancy or birth, and any other pertinent information regarding the delivery were also measured. Based on this criteria, 82 children (61%) had successful outcomes. However, only four of the 134 patients required surgical correction. BoNT-A may be an effective and safe method for treatment in refractory cases of congenital muscular torticollis.

Optimizing Artemia Enrichment: A Low DHA/High EPA Protocol for Enhanced n-3 LC-HUFA Levels to Support Greater Amberjack (Seriola dumerili) Larval Rearing.

Most commercial products available for Artemia sp. enrichment include high levels of docosahexaenoic acid (DHA) to boost its nutritional value, though with limited success. In this regard, the present study evaluated the alternative utilization of eicosapentaenoic acid (20 : 5n-3; EPA) oils to improve the n-3 long-chain highly unsaturated fatty acid content (n-3 LC-HUFA) in enriched Artemia sp. to feed greater amberjack (Seriola dumerili) larvae. Five experimental emulsions containing increasing levels of EPA from 0.8% to 60% of total fatty acids (TFA) and n-3 LC-HUFA (1.3%-70.6% TFA) were formulated. Each diet was fed to greater amberjack larvae (17-35 days posthatch (dph)) in three replicate 200-L tanks. The dietary EPA supplementation significantly improved larval growth during the feeding trial and survival at 35 dph (P < 0.05). In addition, larval fatty acid profiles showed a positive correlation with dietary EPA. Finally, despite the sum of total skeletal anomalies and column anomalies were not significantly affected by dietary EPA, increasing dietary EPA, and n-3 LC-HUFA tended to reduce the incidence of these types of anomalies in greater amberjack larvae at 35 dph. Based on these results, S. dumerili larvae could be successfully grown with low DHA but high EPA-rich oil enrichment products when n-3 LC-HUFA content in Artemia sp. is maintained in sufficient amounts.

Skeletal Dysplasia: A Case Report.

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.

Protective effect of quercetin on fetal development and congenital skeletal anomalies against exposure of pregnant Wistar rats to crude oil vapor.

Epidemiological evidence indicates a relationship between maternal exposure to crude oil vapors (COV) during pregnancy and adverse pregnancy outcomes. Quercetin (QUE) is a plant flavonoid with purported antioxidant and anti-inflammatory effects, which has been shown to prevent birth defects. This study was aimed to investigate the protective role of QUE on fetal development and congenital skeletal anomalies caused by exposure of pregnant rats to COV. Twenty-four pregnant Wistar rats were randomly categorized into four groups of control, COV, COV + QUE, and QUE (50 mg/kg). The inhalation method was used to expose pregnant rats to COV from day 0 to 20 of pregnancy, and QUE was administered orally during this period. On day 20 of gestation, the animals were anesthetized and a laparotomy was performed, and then the weight and crown rump length (CRL) of the fetuses were determined. Skeletal stereomicroscopic evaluations of fetuses were performed using Alcian blue/Alizarin red staining method, and the expression of osteogenesis-related genes (Runx2 and BMP-4) was evaluated using qPCR. This study showed that prenatal exposure to COV significantly reduced fetal weight and CRL, and expression of Runx2 and BMP-4 genes. Moreover, COV significantly increased the incidence of congenital skeletal anomalies such as cleft palate, spina bifida and non-ossification of the fetal bones. However, administration of QUE with exposure to COV improved fetal bone development and reduced congenital skeletal anomalies. QUE can ameliorate the teratogenic effects of prenatal exposure to COV by increasing the expression of osteogenesis-related genes.

Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature

BackgroundKBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures....

BMP2 is a potential causative gene for isolated dextrocardia situs solitus

BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal.The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. However, due to a small number of reported patients with BMP2 haploinsufficiency, the genotype and phenotype correlations are not fully understood.We experienced a family of BMP2 haploinsufficiency with a novel frameshift variant NM_001200.4: c.231dup (p.Tyr78Leufs*38) which was predicted to be “pathogenic” by the American College of Genetics and Genomics (ACGM) criteria. In addition to short stature, impaired hearing ability and minor skeletal deformities, the proband exhibited isolated dextrocardia situs solitus without cardiac anomalies and abnormal locations of other visceral organs. Our study would shed light on the crucial role of BMP2 in determining the cardiac axis, and further studies are needed to assemble more cases to elucidate BMP2 role in human heart development.

E49 Behçet's disease associated with Warkany syndrome: a case report

Abstract Background Behçet's disease is a rare chronic, relapsing, multisystem vasculitis characterized by mucocutaneous lesions, articular, ocular, vascular, and central nervous system manifestations, of which pediatric forms may be syndromic. Warkany syndrome is a rare genetic anomaly defined by trisomy 8, characterized clinically by facial dysmorphia, mild intellectual disability, and skeletal anomalies. Aim We report the case of a 9-year-old boy diagnosed with Behçet's disease and whose examination revealed an associated Warkany syndrome. Observation the boy was from a non-consanguineous marriage, correctly vaccinated, with a history of congenital dislocation of the hip operated at the age of 3 years and obstruction of the lacrimal duct operated at the age of 6 years, who presented with chronic bilateral synechial pan uveitis, recurrent oral aphthosis (&amp;gt;3 times a year), multiple dysostosis with chronic diffuse arthralgias: hip, knees, shoulders. The clinical examination reveals a facial dysmorphia (elongated skull, high and prominent forehead, hypertelorism, sunken eyes, wide nose with anteverted nostrils, micrognathia with eversion of the lower lip, large ears with a thick rim), organomegaly (hepatosplenomegaly, large kidneys), a moderate intellectual deficit and deep palmar and plantar folds Auditory evoked potential finds bilateral deafness. Inflammatory workup was positive, HLAb51 typing was positive. MPS enzyme assay is normal. Genetic study: not done due to lack of means. Conclusion Behçet's disease in children can be associated with other genetic syndromes, it remains to be seen if it is a simple fortuitous association.

Coexistence of Slipped Capital Femoral Epiphysis and multiple endocrine neoplasia type 2B (MEN2B) - a case report

Introduction: MEN 2B syndrome is distinguished by the occurrence of medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid features, and skeletal anomalies, including kyphoscoliosis, joint laxity, pes cavus, and, in a smaller number of cases, slipped capital femoral epiphysis (SCFE).&#x0D; Case report: We describe a case report of a 15-years-old patient with the diagnosis of the MEN2B syndrome with a rare manifestation of Slipped Capital Femoral Epiphysis (SCFE). A 15-year-old female presented to the orthopedics out-patient department (OPD) with complaints of pain around the right hip and knee and walking with a limp for approximately four months. Additionally, the feeling of enlarged thyroid gland was reported. X-ray confirmed the presence of the SCFE, while thyroid biopsy revealed the presence of medullary thyroid cancer (MTC). Thus, the diagnosis of MEN2B was made.&#x0D; Conclusion: Slipped capital femoral epiphysis (SCFE) can occasionally be a manifestation of MEN 2B syndrome. It is important for physicians to be aware of this association, as it can contribute to the early detection of a potentially life-threatening condition.

An analysis of factors affecting survival in prenatally diagnosed omphalocele.

To estimate factors affecting survival in prenatally diagnosed omphalocele, factors predicting genetic abnormalities, and association of omphalocele and specific groups of anomalies. A retrospective observational study was performed, analyzing data of all omphalocele cases diagnosed prenatally in the perinatology clinic of a referral center. Demographic data, characteristics of the omphalocele (size,content, associated anomalies), results of genetic testing, pregnancy outcomes and postnatal outcomes were analyzed. Sixty-nine fetuses with omphalocele were included. The prevalence of omphalocele in livebirth was 0.007 %. Overall survival during the study period was 73.9 %.Twenty-eight (71.7 %) out of 39 cases with associated anomalies who were born live, survived, whereas survival was 85.7 % in the isolated cases. The most common anomaly associated with omphalocele were cardiac defects with 42 %; followed by placental or umbilical cord anomalies (28.9 %), skeletal defects (27.5), genitourinary anomalies (20.2 %), central nervous system (18.8 %) and facial anomalies (7.2 %), respectively. Eighty-five percent of the fetuses had at least one additional anomaly or ultrasound finding. Skeletal abnormalities and staged surgical repair of omphalocele were associated with survival. Associated skeletal anomalies and staged repair significantly increase the risk of postnatal death (OR: 4.6 95 % CI (1.1-19.5) and (OR: 10.3 95 % CI (1.6-63.9), respectively). Associated skeletal abnormalities and staged surgical repair are negatively associated with postnatal survival.

Swim bladder inflation failure and associated spinal deformities in giant grouper Epinephelus lanceolatus

Giant grouper (Epinephelus lanceolatus, GG) is a valuable aquaculture species in Southeast Asia. Its farming is challenging, and the occurrence of spinal deformities is one of the bottlenecks found in aquaculture production. This study investigated the development of the swim bladder (SB) in GG and a possible causative relationship between failing to inflate the SB and spinal deviations in juvenile fish. The study of the ontogeny of the SB in GG revealed that the organ is connected through the pneumatic duct to the digestive tube from day 4 to day 7 post hatching (DPH). Repeated observations of larvae over this period showed that GG SB inflation period commences on day 5 DPH and lasts until the end of day 7 DPH. However, a proportion of day 7 DPH larvae failed to inflate their SB showing unorganised acidophilic tissue in the lumen of the organ. Assessment of skeletal anomalies in post metamorphic fish (42 DPH) revealed a relationship between the lack of an inflated SB and anomalies in the caudal region; more specifically, the urostyle (p < 0.05). Morphological assessment of juvenile fish showed a direct relationship between the lack of an inflated SB and lordotic/kyphotic anomalies. This was confirmed by X-ray of fish with and without an inflated SB following separation by hypersaline flotation. These findings show that SB inflation failure is the major contributing factor to spinal anomalies in GG. Also, this study described the timing of the SB inflation period in GG and its development.

Assessing the economic impacts of severe skeletal anomalies in Mediterranean hatcheries culturing seabream and seabass

AbstractThe economic impact of skeletal anomalies in aquaculture farming is a significant issue for the industry, as deformed fish are frequently discarded because of their low survival rate and a variety of other disadvantages, including increased costs, consumer distrust of aquaculture products, and ethical concerns. The goal of this article is to propose a method for calculating the direct costs of severe skeletal anomalies in typical Mediterranean seabream and seabass aquaculture hatcheries using a deterministic static model programmed in MATLAB that simulates their annual operation. Our findings suggest that larger hatcheries experience higher direct costs associated with severe skeletal anomalies but have better financial stability and significantly higher expected profits. Mean results indicate that the annual economic losses of severe skeletal anomalies for seabream and seabass Mediterranean aquaculture are 22.88 million euros per year for a scenario of low severe skeletal anomalies, 65.34 million euros per year for a scenario of medium severe skeletal anomalies, and 115.98 million euros per year for a scenario of high severe skeletal anomalies. Furthermore, some options for increasing the financial stability of the hatcheries are to increase the sale price of fingerlings, reduce the feed conversion ratio, and reduce the feed unit cost.

Successful surgical treatment of omphalocele with umbilical evagination of the bladder: an extremely rare presentation of neonatal case

BackgroundA few cases of small omphalocele with umbilical evagination of the bladder have been reported. However, its embryology is yet to be elucidated. Only a few reports have indicated the existence of urachal anomalies and umbilical cysts related to bladder evagination. The incidence of urachal anomalies at birth is reported to be 1 in 5000–8000 live birth, and urachal aplasia is rare. Herein, we report a rare, novel case of urachal aplasia.Case presentationWe encountered a small omphalocele with bladder evagination associated with urachal aplasia for which the neonate underwent surgery one day after birth. The patient was a one-day-old boy with a prenatally diagnosed omphalocele. A fetal magnetic resonance image (MRI) scan (25 weeks of gestation) revealed a 30 × 33 mm (approximately 1.3 in.) cystic lesion which was suspected to be an umbilical cyst. The baby was born vaginally at 38 weeks, weighing 2956 g. An omphalocele (hernial orifice diameter, 4 cm × 3 cm) with bladder prolapse was recognized. After sac excision, the prolapsed bladder was resected and closed with two-layer sutures. In order to secure sufficient bladder capacity, we estimated the minimum residual volume as 21 ml after bladder plasty. The remaining bladder capacity was confirmed to be 30 ml by injecting a contrast dye and saline into the bladder. The neonate had no associated cardiac urogenital or skeletal anomalies. Postoperative course was uneventful. The patient was regularly followed up for two years after surgery and underwent umbilicoplasty. He had no trouble with urinary function.ConclusionIn this case, we experienced extremely rare condition of a small omphalocele with bladder evagination associated with urachal aplasia and reviewed 7 case reports of anomalies similar to those in the present case. Umbilical cord cysts may be an informative indicator of these symptoms in utero. Therefore, ultrasonography scans should be conducted until delivery, despite the spontaneous disappearance of cord cysts.

Rare variant enrichment analysis supports GREB1L as a contributory driver gene in the etiology of Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was used to further reproduce GREB1L findings in diverse genetic backgrounds. Proband and OMIM phenotypes annotated using the Human Phenotype Ontology were analyzed to quantitatively delineate the phenotypic spectrum associated with GREB1L variant alleles found in our MRKH cohort and those previously published. This study reports 18 novel GREB1L variant alleles, 16 within a multiethnic MRKH cohort and two within a congenital scoliosis cohort. Cohort-wide analyses for a burden of rare variants within a single gene identified likely damaging variants in GREB1L (MIM: 617782), a known disease gene for renal hypoplasia and uterine abnormalities (MIM: 617805), in 16 of 590 MRKH probands. GREB1L variant alleles, including a CNV null allele, were found in 8 MRKH type 1 probands and 8 MRKH type II probands. This study used quantitative phenotypic analyses in a worldwide multiethnic cohort to identify and strengthen the association of GREB1L to isolated uterine agenesis (MRKH type I) and syndromic MRKH type II.

Accuracy of Multimodality Fetal Imaging (US, MRI, and CT) for Congenital Musculoskeletal Anomalies.

Ultrasonography (US) is the first-line diagnostic tool used to assess fetal musculoskeletal (MSK) anomalies. Associated anomalies in other organ systems may benefit from evaluation via Magnetic Resonance Imaging (MRI). In this study, we compared the diagnostic accuracy of US and MRI to diagnose fetal MSK (primary objective) and non-MSK anomalies (secondary objective). We describe additional findings by low-dose computerized tomography (CT) in two cases incompletely characterized via US and MRI. This was an IRB-approved retrospective study of consecutive patients with suspected fetal MSK anomalies examined between December 2015 and June 2020. We compared individual MSK and non-MSK anomalies identified via US, MRI, and CT with postnatal outcomes. Sensitivity and specificity for US and MRI were calculated and compared. A total of 31 patients with 112 MSK and 43 non-MSK anomalies were included. The sensitivity of MRI and US for MSK anomalies was not significantly different (76.6% vs. 61.3%, p = 0.3). Low-dose CT identified eight additional skeletal anomalies. MRI diagnosed a higher number of non-MSK anomalies compared to US (81.4% vs. 37.2%, p < 0.05). Fetal MRI and US have comparable sensitivity for MSK anomalies. In selected cases, low-dose CT may provide additional information. Fetal MRI detected a larger number of non-MSK anomalies in other organ systems compared to US. Multimodality imaging combining all the information provided by MRI, US, and CT, if necessary, ultimately achieved a sensitivity of 89.2% (95% CI: 83.4% to 95.0%) for the diagnosis of musculoskeletal anomalies and 81.4% for additional anomalies in other organs and systems.

DIVERSE NEUROLOGICAL MANIFESTATION OF HYPERIMMUNOGLOBULIN-E SYNDROME: A CASE SERIES

Hyper-immunoglobulin E (IgE) is a disorder of immune system characterized by assemblage of symptoms including recurrent skin and pulmonary infections, skeletal anomalies and elevated serum IgE (&gt;2000 IU/ml). More recently, apart from the typical features, neurological manifestations have also been described including central nervous system infections, facial nerve palsy and demyelinating disorders. Here we describe three patients with hyper IgE syndrome having diverse neurological manifestation varying from CNS infection to basal ganglia stroke and progressive leukoencephalopathy.

POSITION OF HEADS OF THE TEMPOROMANDABULARY JOINT AND LINEAR DIMENSIONS OF UPPER RESPIRATORY TRACT IN PATIENTS WITH SKELETAL SAGITAL BITE ANOMALIES

Maxillofacial anomalies not only affect aesthetics but also contribute to temporomandibular joint disease. The position of the temporomandibular joint and occlusal factors can influence the airway patency therefore medical interventions should aim at restoring normal breathing, treating TMJ and muscles, and then correcting the occlusion. The aim of this study is to investigate the relationship between the position of the lower jaw, position of TMJ heads, and changes in upper respiratory tract in patients with Class I and II skeletal sagittal bite anomalies according to Angle's classification.&#x0D; Cone-beam computer tomograms of 64 patients were analyzed. The patients were divided into two groups based on the ANB angle. The position of the temporomandibular joint heads was determined using N. Gelb's method in the mid-sagittal plane, while the linear parameters of the upper respiratory tract were assessed using the McNamara method. Regardless of the bite pathology, only 12.5% of patients (n=8) exhibited the correct symmetrical position of the TMJ heads on both sides according to the Gelb grid. In the 1st group, the average width of the upper and lower parts of the pharynx measured by the McNamara method was 17.41±0.44mm and 10.1±0.73mm, respectively. In the 2nd group, the average width of the upper part was 15.82±0.61mm, and the lower part measured 10.25±0.51mm. Among orthodontic patients with Class I and II bite anomalies, only a small percentage (12.5%) was found to have the correct and symmetrical position of the temporomandibular joint. The reduction in the width of the lower respiratory tract in these patients may be associated with posterior displacement of the temporomandibular joint heads.

The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder

De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause "neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities." Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.). Using 3D protein structure analysis and an innovative dual Drosophila gain-of-function assay, we demonstrated a disruptive effect of 11 missense/in-frame indels located in or near the enzymatic JmJC or Zn-containing domain of KDM6B. Consistent with the role of KDM6B in human cognition, we demonstrated a role for the Drosophila KDM6B ortholog in memory and behavior. Taken together, we accurately define the broad clinical spectrum of the KDM6B-related NDD, introduce an innovative functional testing paradigm for the assessment of KDM6B variants, and demonstrate a conserved role for KDM6B in cognition and behavior. Our study demonstrates the critical importance of international collaboration, sharing of clinical data, and rigorous functional analysis of genetic variants to ensure correct disease diagnosis for rare disorders.

Rare causes of congenital neonatal nasal obstruction leading to respiratory distress at birth and its management: A case series

Neonatal nasal obstruction may present as an acute respiratory emergency. Neonates primarily are obligate nasal breathers. Hence, any nasal obstruction whether arising due to skeletal or anatomical anomalies or due to nasal mass or cyst can present with cyanosis, stridor, feeding problems, and/or failure to thrive. Although choanal atresia remains one of the most diagnosed nasal anatomical anomalies leading to this problem; other rare causes of neonatal nasal obstruction, namely, midnasal stenosis, pyriform aperture stenosis, congenital nasal mass, or cyst should also be considered. Hence, a thorough evaluation with diagnostic nasal endoscopy along with an imaging modality (computed tomography/magnetic resonance imaging) is warranted. Management whether conservative or surgical intervention is guided by the severity and nature of the symptoms. This series highlights our experience of four different case scenarios of respiratory distress arising out of nasal anatomical anomalies and its subsequent management and outcome.

Evaluation of dental and skeletal effects of the asymmetric rapid maxillary expansion appliance: A three-dimensional finite element study.

Transverse maxillary deficiency is one of the most common skeletal anomalies. The incidence of posterior crossbite caused by maxillary deficiency is between 2.7% and 23.3%. Unilateral posterior crossbite is more common than bilateral crossbite. The most common treatment for skeletal posterior crossbite is rapid maxillary expansion (RME), in which the base of the maxillary bone is expanded by separating the midpalatal suture. This study compares the biomechanical effects of three different RME appliances, especially the effects on the midline, and evaluates the usability of the modified asymmetric RME (ARME) appliance for treating unilateral crossbites. Three scenarios were created with skull models using three different appliances: (1) conventional-bonded RME appliance; (2) full-cap splint RME appliance, with all teeth covered with acrylic; and (3) ARME, with all teeth on the right side and premolars and molars on the left side covered with acrylic. The finite element method was used to assess stress levels and displacements in all models after applying a 5-mm horizontal displacement to the RME screw. The lateral transverse movement of the first molars was greater with the conventional RME appliance than with the full-cap splint RME appliance. The lateral transverse movement of the first molar was greater on the left than on the right side with the ARME. The lateral transverse movement of the central incisors was greater with the full-cap splint RME appliance than with the conventional RME appliance. The lateral transverse movement of the central incisor was greater on the right than on the left side with the ARME. Asymmetrical RME appliance increases unilateral expansion compared to other appliances. Therefore, it should be used in cases of unilateral posterior crossbite. This appliance can also successfully treat posterior crossbite with upper midline deviation, since it corrects the shifted midline.

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum

PurposeBone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells. In humans, BMP2 variants result in a multiple congenital anomaly syndrome through a haploinsufficiency mechanism. We sought to expand the phenotypic spectrum and highlight phenotypes of patients harboring monoallelic missense variants in BMP2. MethodsWe used retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these with published cases. Patient-derived missense variants were modeled in zebrafish to examine their effect on the ability of bmp2b to promote embryonic ventralization. ResultsThe presented cases recapitulated existing descriptions of BMP2-related disorders, including craniofacial, cardiac, and skeletal anomalies and exhibit a wide phenotypic spectrum. We also identified patients with neural tube defects, structural brain anomalies, and endocrinopathies. Missense variants modeled in zebrafish resulted in loss of protein function. ConclusionWe use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.