Skeletal Anomalies Research Articles

Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Assessment of coral diseases in the shallow reefs of Aka-jima Marine Reserve (AMR), with a brief geographic perspective of disease occurrence throughout the larger Kerama-Shoto Marine National Park (KMNP), Okinawa, Japan

This study reports on the observation of coral diseases within the shallow/intertidal water habitat of the Akajima Marine Reserve (AMR), located within the Keramashoto Marine National Park (KMNP) of Japan. Major coral genera and species assessed during the survey included Montipora spp., Porites spp., Isopora palifera, Acropora spp., as well as other. Observed diseases and health conditions included Black Band Disease (BBD) in Montipora as well as in Goniopora, Skeletal Growth Anomalies (GAs) in Acropora, Montipora, Porites, Isopora and Astreopora, Terpios hoshinota covering Acropora, Montipora and Seriatopora, as well as bleaching, discoloration, and other compromised health signs. This field study recorded the presence of GAs in the genus Leptastrea for the first time within the Japanese Archipelago. The novelty in this study is reporting unreported genera to be infested with certain disease conditions, further this study demonstrates how surveys in previously poorly studied areas or habitats can reveal important information pertaining to coral diseases, thus helping to fill existing knowledge gaps. Another important aspect of this study is, we provide a review of the distribution of coral diseases within the KMNP based on our results and previous reports. Being a rapid survey, the dynamics of these diseases were not assessed, while the major cause(s) of the diseases remains to be identified. In general, climate change-related aspects including rises in sea surface temperatures, as well as other factors such as host density may be responsible for disease prevalences in the region.

Biotinidase Deficiency and Aplasia Cutis Congenita with Ecterodactyly Syndrome (ACCES) in a case of Moya Moya Disease: A Missing Link

Biotinidase Deficiency (BD) is a rare autosomal recessive disorder caused by mutations in the BTD gene, leading to impaired biotin recycling and disruption in energy metabolism, oxidative stress, and blood-brain barrier function. This condition increases the risk of neurovascular events such as strokes. In parallel, the UBA2 gene's loss of function, through various mutations, results in Aplasia Cutis Congenita with Ectrodactyly (ACCES) syndrome, an autosomal dominant disorder with highly variable expressivity. ACCES syndrome commonly presents with scalp defects and less frequently with ectrodactyly, alongside other subtle skeletal anomalies, early growth deficiency, and neurodevelopmental delay. This case report discusses a 6-year-old child presenting with an acute stroke and distinct dysmorphic features, highlighting a rare association between Biotinidase Deficiency and ACCES syndrome, which likely contributed to the development of Moya Moya Disease (MMD), a rare progressive cerebrovascular disorder. The case suggests that the combination of neurovascular stress due to both BD and ACCES may increase the risk of stroke and MMD in affected individuals. This underscores the importance of recognizing overlapping genetic conditions that could lead to severe neurovascular complications.

Association of LONP1 gene with epilepsy and the sub-regional effect

The LONP1 gene encodes Lon protease, which is responsible for degrading damaged or misfolded proteins and binding mitochondrial DNA. Previously, LONP1 variants have been identified in patients with cerebral, ocular, dental, auricular, and skeletal anomalies (CODAS syndrome) and mitochondrial diseases. Seizures were occasionally observed. However, the association between LONP1 and epilepsy remains elusive. In this study, we performed trio-based whole-exome sequencing in a cohort of 450 patients with unexplained epilepsy and identified four pairs of compound heterozygous LONP1 variants in four unrelated cases. All patients exhibited good responses to anti-seizure medications and demonstrated no developmental delay or intellectual disabilities. The variant allele frequencies observed in this study were absent or low in the general population and were significantly lower than those of benign variants. At least one variant in each biallelic pair affected hydrogen bonding and/or altered protein stability. The CODAS syndrome-associated variants were concentrated in the AAA+ module, especially the α domain. Four of the five mitochondrial disease-associated variants were located in the AAA + domain and the NTD5H and NTD3H subdomains. In contrast, each of the biallelic variants from the patients with pure epilepsy had one variant located in the linker domain, and the other variant located in the mitochondrial targeting sequence or P domain. This study suggested that LONP1 gene is potentially a novel candidate gene for pure epilepsy. The phenotypic variation is associated with the sub-regional effects of variants.

Factors Associated with Postoperative Complications After Congenital Duodenal Obstruction Surgery: A Retrospective Study.

Background and Objectives: Duodenal atresia and stenosis are common causes of intestinal obstruction. Associated anomalies significantly influence early postoperative mortality, while postoperative complications impact long-term survival. Materials and Methods: Over a 13-year period from January 2010 to August 2023, a total of 74 infants and children with congenital duodenal obstruction were treated at "Grigore Alexandrescu" Children's Emergency Hospital and met the inclusion criteria. All patients diagnosed with duodenal obstruction (both instrinsic and extrinsic causes) were included. Analysed data included congenital anomalies, Apgar scores, birth weights, surgical techniques, and complications. Results: The associated anomalies included cardiac (n = 33), Down syndrome (n = 13), neurological (n = 11), pulmonary (n = 7), renal (n = 4), skeletal (n = 1), and gastrointestinal and hepatobiliopancreatic anomalies (n = 25). In total, 12 patients experienced perioperative ventilation problems. Early postoperative complications (within 30 days) occurred in 21 patients, while 6 had late postoperative complications (after 30 days). Among non-surgical complications, we noted ventilation problems, sepsis (n = 7), and pneumothorax (n = 1). Surgical complications included adhesive bowel obstruction (n = 7), incisional hernia (n = 3), peritonitis (n = 3), dysfunctional duodenoduodenostomy or duodenojejunostomy (n = 3), pneumoperitoneum (n = 5), enteric fistula (n = 3), and volvulus (n = 4). Conclusions: Surprisingly, this retrospective study revealed that an Apgar score below 8, along with neurological and pulmonary abnormalities, is associated with postoperative complications. Conversely, other congenital anomalies, low birth weight, and age at admission do not serve as prognostic factors.

Optimizing care for MRKH patients: From malformation screening to uterus transplantation eligibility.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with utero-vaginal aplasia is the most severe form of the Müllerian duct anomalies and can be associated with extra-genital abnormalities such as renal or skeletal anomalies, hearing loss, or cardiac defects. The past two decades have witnessed significant advances both in understanding the etiologies of MRKH and in the development of fertility treatments such as uterine transplantation. The present work aimed to determine the rate of women with MRKH syndrome who underwent optimal initial management (after comprehensive malformation assessment) and to establish the rate of patients eligible for uterine transplantation (i.e., those with a vaginal length ≥7 cm without reconstruction using a bowel segment, and an anti-Müllerian hormone level >1.5 ng/mL before 35 years). Cohort study of 85 women with MRKH syndrome consulting in our tertiary center. 62.4% of women with MRKH syndrome had an exhaustive malformative evaluation according to the French guidelines (Protocole National de Diagnostic et de Soin [PNDS]), of which 76.5% had associated malformations (MRKH type II). Pedigree, when available, showed a family history of infertility or a urogenital tract spectrum anomaly in 60% of cases. Concerning the uterine transplantation selection criteria, when evaluated, 22.6% of women had an anti-Müllerian hormone level <1.5 ng/mL and 36% a vaginal length <7 cm. On the 21 women with complete evaluation of both primary and secondary outcomes, 14 of them would be eligible for a uterine transplantation program at the time of consultation according to the main inclusion criteria of uterine transplantation program. Women with MRKH syndrome are often inadequately explored for associated malformations. Early assessment and monitoring of the ovarian reserve is key for fertility preservation, especially in the era of uterine transplantation.

Fixed Prosthodontic Rehabilitation of a Patient with Cleidocranial Dysplasia: A Case Report

Introduction Cleidocranial Dysplasia (CCD) is a rare congenital disease characterized by skeletal and dental anomalies. Clinical findings of CCD patients include low facial height, pseudoprognathism, unerupted teeth, an excessive deep bite, chewing difficulties, and unsatisfied dentofacial appearance. These patients’ dental treatments present a substantial challenge. Case Representation This case report describes the prosthodontic treatment of a 29-year-old male CCD patient using porcelain-fused-to-metal restorations. The avoidance of a surgical procedure serves to minimize the potential for complications and expedites the attainment of outcomes with greater celerity. Throughout the follow-up period of 1 year, the patient maintained good periodontal health. The restoration of masticatory function and enhancement of facial esthetics were successfully achieved and the patient expressed a high degree of satisfaction with the outcome of the treatment. Conclusion The use of fixed prostheses in CCD patients is a treatment modality that resolves many of the issues caused by the surgical approach.

Simultaneous CNV-seq and WES: An effective strategy for molecular diagnosis of unexplained fetal structural anomalies

BackgroundFetal structural anomalies are detected by ultrasound in approximately 3 % of pregnancies. Numerous genetic diagnostic strategies have been widely applied to identify the genetic causes of prenatal abnormalities. We aimed to assess the value of simultaneous copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in diagnosing fetuses with structural anomalies. MethodsFetuses with structural anomalies detected by ultrasound were included for eligibility. After genetic counseling, WES and CNV-seq were performed on DNA samples of fetuses and their parents. All detected variants were evaluated for pathogenicity according to ACMG criteria, with the final diagnosis was determined based on ultrasound results and relevant family history. ResultsThe diagnostic rate of 174 fetuses with prenatal ultrasound abnormalities was 26.44 %, higher than that achieved through either CNV or WES analysis alone. Furthermore, the highest diagnostic rate was observed in fetuses with multiple system anomalies, accounting for 50 % of the total diagnostic yield, followed by skeletal system anomalies at 45.45 %. Three cases with multiple system abnormalities were found to have a dual diagnosis of pathogenic CNVs and SNV variants, representing 1.72 % of the total cohort. 38 pregnant women in their third trimester of pregnancy (27 weeks+) participated in this study, and 23.68 % received a confirmed genetic diagnosis. Finally, 31 women (67.39 %) voluntarily terminated their pregnancy following the testing and extensive genetic counseling. ConclusionsOur study demonstrated that the simultaneous CNV-seq and WES analyses are beneficial for the molecular diagnosis of underlying unexplained structural anomalies in fetuses. This strategy is more efficient in elucidating prenatal abnormalities with compound problems, such as dual diagnoses. Furthermore, the simultaneous strategy has a shorter turnaround time and is particularly suitable for families with structural anomalies found in the third trimester of pregnancy.

Three dimensional radiological assessment of the mediopalatine suture ossification and its correlation with biological age and orthodontic anomaly

Introduction. Evaluating the ossification of the mediopalatine suture is crucial when considering Rapid Maxillary Expansion (RME) as a treatment option. Three-dimensional imaging, such as CBCT, enhances clinical practice in orthodontics by enabling personalized treatment based on individual patient characteristics. Objective. This study aimed to assess the morphology and degree of ossification/skeletal maturation of the mediopalatine suture using 3D imaging (CBCT). The secondary aim was to correlate the stages of suture maturation with patient age and skeletal anomalies. Material and method. CBCT images from 56 patients (aged 11 to 65 years) were analyzed. The mediopalatine suture maturation stages were determined according to Angelieri’s classification. Dental anomalies were diagnosed using comprehensive documentation. Statistical analysis was performed to correlate maturation stages with patient age and dental anomalies. Results. There was a weak and statistically non-significant negative correlation between patient age and suture maturation stage. Gender did not significantly influence the ossification of the mediopalatine suture. Conclusions. These findings suggest that the degree of ossification of the mediopalatine suture is independent of both the age of the patients and the presence of orthodontic anomalies.

Diseases of the primary cilia: a clinical characteristics review.

Ciliopathies encompass a broad spectrum of diseases stemming from dysfunction of the primary (non-motile) cilia, present on almost all cells in the human body. These disorders include autosomal dominant and recessive polycystic kidney diseases, nephronophthisis, and multisystem ciliopathies such as Joubert, Meckel, Bardet-Biedl, Alström, oral-facial-digital syndromes, and skeletal ciliopathies. The majority of these ciliopathies are associated with fibrocystic kidney disease resulting in progressive kidney dysfunction. In addition, many ciliopathies are associated with extra-renal manifestations including congenital hepatic fibrosis, retinal dystrophy, obesity, and brain and skeletal anomalies. The diagnoses may be challenging due to their overlapping clinical features and molecular heterogeneity. To date, over 190 genes encoding proteins that localize to the primary cilia have been identified as disease-causing. This review will discuss the clinical features of the most frequently encountered disorders of primary cilia.

The Role of Plain Radiography in Assessing Aborted Foetal Musculoskeletal Anomalies in Everyday Practice.

Conventional radiography is widely used for postmortem foetal imaging, but its role in diagnosing congenital anomalies is debated. This study aimed to assess the effectiveness of X-rays in detecting skeletal abnormalities and guiding genetic analysis and counselling. This is a retrospective analysis of all post-abortion diagnostic imaging studies conducted at a centre serving a population of over 300,000 inhabitants from 2008 to 2023. The data were analysed using descriptive statistics. X-rays of 81 aborted foetuses (total of 308 projections; mean: 3.8 projections/examination; SD: 1.79) were included. We detected 137 skeletal anomalies. In seven cases (12.7%), skeletal anomalies identified through radiology were missed by prenatal sonography. The autopsy confirmed radiological data in all cases except for two radiological false positives. Additionally, radiology failed to identify a case of syndactyly, which was revealed by anatomopathology. X-ray is crucial for accurately classifying skeletal abnormalities, determining the causes of spontaneous abortion, and guiding the request for genetic counselling. Formal training for both technicians and radiologists, as well as multidisciplinary teamwork, is necessary to perform X-ray examinations on aborted foetuses and interpret the results effectively.

Detection Rate of Fetal Anomalies in Early Mid-Trimester Compared to Late Mid-Trimester Detailed Scans: Possible Implications for First-Trimester Sonography.

Objective: A late mid-trimester fetal organ scan (lMTS) is recommended between 18 and 22 weeks of pregnancy. Evidence has been accumulating on the effectiveness of first-trimester anatomy scans. Early mid-trimester fetal scans (eMTSs; 14-17 weeks) may have the advantage of visualization of most organs, hence allowing earlier genetic assessment and decision making. Our aim is to examine the effectiveness of eMTSs in identifying fetal anomalies compared to lMTSs. Methods: A retrospective study was conducted based on data from the multidisciplinary prenatal diagnosis clinic in a tertiary center. During the study period (2011-2021), an out-of-pocket eMTS in a community setting was offered routinely to the general population. Women who had previously undergone an eMTS and were later assessed due to a fetal anomaly in our clinic were included in the study. The cohort was divided into two groups according to whether the anomaly had been detected during the eMTS. We then compared the groups for factors that may be associated with anomaly detection in eMTSs. We used t-tests and chi-square tests, for quantitative and qualitative variables, respectively, to determine variables related to eMTS anomaly detection, and logistic regression for multivariate analysis. Results: Of 1525 women assessed in our multidisciplinary clinic, 340 were included in the study. The anomaly detection rate of the eMTS compared to the lMTS was 59.1% The eMTS detection rates for specific organ systems were as follows: skeletal, 57%; cardiac, 52%; congenital anomalies of the kidneys and urinary tract (CAKUT), 44%; central nervous system, 32.4%; chest, 33%; and abdominal, 28%. In multivariate analysis, abnormal first-trimester screening (aOR 3.2; 95%CI 1.26-8.08) and multiple anomalies (aOR 1.86; 95%CI 1.02-3.37) were found to be associated with eMTS anomaly detection. Conclusions: The eMTS detection rate was nearly 60% and was most accurate in detecting skeletal, cardiac, and CAKUT anomalies. Since the eMTS was community-based, this rate likely reflects a "real-world" scenario. Our findings support consideration of performing an eMTS or first-trimester scan routinely for earlier diagnosis and decision making, as an adjunctive to lMTSs. Future studies will examine the cost-effectiveness of early scans.

Evaluation of masticatory muscles in patients with different sagittal direction skeletal anomalies by ultrasonography and ultrasonographic elastography.

The aim of this study was to evaluated the masseter, anterior digastric and geniohyoid muscles of individuals with similar growth and developmental periods but different sagittal skeletal malocclusions using ultrasonography and ultrasonographic elastography and to make interclass assessments. In this study, ultrasonography and ultrasonographic elastography records of 30 Class I individuals (17 females, 13 males), 30 Class II individuals (14 females, 16 males), and 27 Class III individuals (12 females, 15 males) in the normodivergent and growth development periodwere used. The masseter, anterior digastric, and geniohyoid muscles of individualswere examinedusing ultrasonography and ultrasonographic elastography, andcomparisons were madebetween the classes. Statistical analysis was accomplished by Mann Whitney U, One-way ANOVA, Kruskal Wallis H tests. Interclass differences were foundin ultrasonography and elastography measurements of the masseter muscle. However, no differences were observed in ultrasonography measurements of the auxiliary masticatory muscles, whereas differences were seen only in the geniohyoid muscle in elastography measurements among the classes (p<0.05). Individuals with different sagittal skeletal malocclusions during growth and development exhibited similar muscle sizes and elasticities, approximately close to each other.

Monostotic fibrous dysplasia of jaw bones: a case series

Abstract Background Fibrous dysplasia (FD) is a benign fibro-osseous lesion, a skeletal developmental anomaly of the bone-forming mesenchyme. The diagnosis of fibro-osseous lesions, particularly those of the jaw bones, poses significant challenges to clinicians and pathologists since it requires a correlation of clinical, radiological, histological, and surgical findings. Accurate and specific diagnosis is crucial as treatment modalities differ with different fibro-osseous lesions. Methods This retrospective analysis presents a case series of a rare condition of monostotic FD in the maxillofacial region affecting jaw bones diagnosed and/or treated over period of 10 years. Results Five cases of monostotic FD were diagnosed and treated between a period of 2013 and 2023. The cases from the 2nd to 8th decade were included in the analysis with equal involvement of males and females. Out of five cases, four cases were involving maxilla and 1 showed involvement of mandible. Conclusion FD is a rare entity affecting the jaw bones which often lead to disfigurement of face. Early detection is warranted to decrease potential complications. In addition, genetic analysis could help in understanding the occurrence in certain population.

Antenatal unilateral upper limb acromesomelic dysplasia.

Acromesomelic dysplasia (AMD) is an umbrella term given to a heterogeneous group of progressive skeletal disorders characterized by short limbed dwarfism associated with disproportionate shortening of middle and distal segments of the upper as well as lower limbs. Although specific skeletal anomalies are difficult to diagnose antenatally, but because of their antenatal and postnatal implications and a possibility of reoccurrence in following pregnancies, such skeletal anomalies need to be actively addressed. A combination of radiologic, pathologic, genetic and molecular investigation prenatally as well as postnatally is required to classify a specific congenital skeletal dysplasia. Once the genetic make-up of fetal skeletal dysplasia is deciphered, a meaningful genetic counselling could be offered for future pregnancies of affected families. We describe a case of primigravida diagnosed with fetal unilateral upper limb AMD on antenatal ultrasound done at early second trimester. The radius and ulna of left upper limb were abnormally short (less than 5th centile of the mean for that gestational age). The left hand was also hypoplastic. Rest of the sonographic anomaly scan was normal. To the best of our knowledge, AMD limited to unilateral upper limb diagnosed antenatally as an isolated finding is not described in the medical literature so far.

Determination of orthodontic anomaly patterns in patients in the Thrace region and assessment of the relationship between orthodontic anomalies and DMFT indices: a retrospective study

OBJECTIVE: The aim of this study was to investigate the prevalence of dental and skeletal anomalies that could be a cause of malocclusion and their relationship with caries distribution in the western region of Türkiye. MATERIALS AND METHOD: A retrospective study was conducted with 1815 digital panoramic and lateral cephalometric radiographs taken from patients, age ranging between 6 and 47 years, who applied for orthodontic treatment. The lateral cephalometric radiographs, panoramic radiographs, and dental records were reviewed according to skeletal anomaly, dental malocclusion (Angle classification), and decay-missing- filling teeth (DMFT) index. Kruskal Wallis test was used in intergroup comparisons of variables that did not show normal distribution, and Dunn’s multiple comparison test was used in subgroup comparisons. The chi-square test and Yates correction were used in comparisons of qualitative data. RESULTS: The mean DMFT of the dental Class I malocclusion group was statistically and significantly lower than Class II division 1 and Class III malocclusion groups (p &amp;lt; 0.05). The mean DMFT index of Class II subdivision malocclusion group was statistically and significantly lower than that of Class III malocclusion group (p &amp;lt; 0.05). The DMFT index was significantly lower in the skeletal Class I group compared to the skeletal Class II and Class III anomaly groups (p &amp;lt; 0.05). CONCLUSION: There is a correlation between DMFT indices and dental malocclusions as well as skeletal anomalies. By correcting dental malocclusions and skeletal anomalies with orthodontic treatment and providing ideal occlusion, it becomes easier for patients to maintain oral hygiene and DMFT indices might decrease.

Clinical and molecular characteristics of Korean patients with Kabuki syndrome.

Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS. This study included 28 Korean patients (14 boys and 14 girls) with KS through molecular genetic testing, including direct Sanger sequencing, whole-exome sequencing, or whole-genome sequencing. The median age at clinical diagnosis was 18.5 months (IQR 7-58 months), and the median follow-up duration was 80.5 months (IQR 48-112 months). Molecular genetic testing identified different pathogenic variants of the KMT2D (n = 23) and KDM6A (n = 3) genes, including 15 novel variants. Patients showed typical facial features (100%), such as long palpebral fissure and eversion of the lower eyelid; intellectual disability/developmental delay (96%); short stature (79%); and congenital cardiac anomalies (75%). Although 71% experienced failure to thrive in infancy, 54% of patients showed a tendency toward overweight/obesity in early childhood. Patients with KDM6A variants demonstrated severe genotype-phenotype correlation. This study enhances the understanding of the clinical and genetic characteristics of KS.

Managing dental and skeletal development in patients with hemifacial microsomia

Hemifacial microsomia (HFM) is a congenital condition characterized by the underdevelopment of one side of the face, impacting the ear, mouth, and jaw areas. This anomaly, second only to cleft lip and palate in prevalence, presents significant challenges in dental and skeletal development. Early diagnosis, primarily through advanced imaging techniques such as 3D computed tomography (CT) scans and magnetic resonance imaging (MRI), is crucial for identifying the extent of anomalies and planning effective interventions. The condition involves complex dental issues including malocclusion, missing teeth, and delayed dental eruption, necessitating early and targeted orthodontic treatments. Functional appliances, space maintainers, and braces are commonly used to guide dental arch development and correct alignment, leveraging the natural growth phase of the patient. Surgical interventions play a pivotal role in managing severe skeletal deformities. Preventive strategies, including regular dental check-ups, proper oral hygiene practices, and preventive treatments such as fluoride applications and dental sealants, are vital in minimizing complications and ensuring long-term oral health. Educating patients and their families on the importance of oral hygiene and routine dental care is crucial for maintaining dental health and preventing future issues. Continuous monitoring and follow-ups allow for timely adjustments to treatment plans, enhancing the effectiveness of interventions and supporting optimal growth and development. Overall, the management of dental and skeletal anomalies in hemifacial microsomia involves a combination of early diagnosis, orthodontic and surgical treatments, and preventive care, all of which are integral to improving outcomes and quality of life for affected individuals.

Correlations of skeletal anomalies of the lower limbs and the mandibular ramus lengths

Correlations of skeletal anomalies of the lower limbs and the mandibular ramus lengths

Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.

Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.