Developmental Anomalies Research Articles

Lobar Emphysema Successfully Operated in an Extreme Premature Neonate

Background: Lobar emphysema in a newborn may be due to a rare congenital developmental anomaly of the lung, termed congenital lobar emphysema (CLE) or may develop secondary to lung damage, especially with positive airway pressures in premature newborns, known as acquired lobar emphysema (LE). They may have overlapping clinical and radiological features. However, surgical lobectomy is required whenever there is significant respiratory compromise. Reports of surgery in LE in extreme preterms are sparse. Clinical Description: A female newborn with gestational age of 28 weeks, weight of 1.180 kg, presented with respiratory distress after birth, initially treated as hyaline membrane disease. With worsening respiratory distress on positive airway pressures, repeat chest X-ray and computed tomography (CT) chest on day 15 of life, suggested possible LE on the left side with the tracheo-mediastinal shift to the right. Management and Outcome: Left thoracotomy and left upper lobectomy was done, following which, there was rapid improvement in respiratory distress, the newborn being extubated after 6 hours, and weaned off oxygen over the next 3 days. The baby was discharged after 8 weeks and at the last follow-up of 3 years of age, the child was growing well with no complications. Conclusion: Preterm neonates with initial radiological features of hyaline membrane disease, requiring prolonged respiratory support, may be harboring other underlying lung anomalies, which are identified by CT chest. Lobar emphysema with tracheo-mediastinal shift warrants prompt surgery, which is feasible and successful, even in a low birth-weight premature infant.

A rare case of Klippel-Trenaunay-Weber syndrome in a child

Klippel-Trenon-Weber syndrome is a rare congenital disorder characterized by polymorphism of clinical manifestations, including vascular malformations, skeletal deformities, facial asymmetry and other developmental anomalies. The study of this syndrome is driven by its rarity, complexity of diagnosis and treatment, and significant impact on the quality of life of patients. Early diagnosis and adequate surgical intervention can significantly improve the prognosis and reduce the risk of serious complications This is a rare congenital disease characterized by a triad of symptoms: angiodysplasia, congenital skeletal anomalies and muscle hypertrophy. This syndrome is caused by a defect in the keratin 13 gene (KRT13), which causes dysfunction of cells of ectodermal origin, including keratinocytes, endothelial cells and ectodermal cells. Clinical symptoms of the syndrome may include hydrocephalus, congenital kidney defects, limb abnormalities, and other pathological changes. Treatment usually depends on the specific symptoms and complications and may include surgery, drug therapy, physiotherapy and rehabilitation. Understanding the genetic mechanisms and factors that cause the syndrome will allow us to develop more effective diagnostic and treatment methods and improve the prognosis for patients. The aim of the study was to demonstrate a clinical case of this extremely rare paediatric pathology, to show the peculiarities of its diagnosis and treatment. The peculiarity of this patient was a deformity (severe thickening) of the right foot at birth. In the process of growth, the deformity of the right foot increased, making it impossible to use standard shoes. The subcutaneous venous network on the right lower limb became stronger. The course of this disease and the treatment performed are described. Keywords: syndactyly, hypertrophy, foot, surgery, limb asymmetry, congenital anomaly.

Cerebrofacial Venous Metameric Syndrome Mimicking Vein of Galen Aneurysmal Malformation

Cerebrofacial venous metameric syndrome (CVMS) is a complex low-flow vascular malformation affecting bone and soft tissues including brain, dura mater, and eye. We show images of CVMS in an 18-month-old boy presenting facial venous malformations, developmental venous anomalies, dural sinus malformations, and dilated great cerebral vein, suggesting a vein of Galen aneurysmal malformation. Although Sturge-Weber syndrome is the most known form of CVMS, its presentations are variable and include several venous malformations. Recognizing the various manifestations of CVMS is necessary for adequate screening, treatment, and follow-up.

Cerebral Doppler imaging in neonates: A guide for clinical application and diagnosis.

Cranial ultrasound reliably diagnoses many neonatal brain disorders. Adding Doppler imaging expands the spectrum by providing information on the status of the vasculature and haemodynamics that may guide further diagnostic and clinical management. Doppler imaging may identify neonates with congenital or acquired vascular abnormalities such as perinatal stroke, sinuvenous thrombosis, vein of Galen malformation, dural sinus malformation, sinus pericranii, and developmental venous anomaly. These entities may need further investigation with complementary imaging modalities such as magnetic resonance imaging and magnetic resonance angiography, or conventional angiography. This review aims to help clinicians to improve their Doppler sonography knowledge and skills in order to use this helpful tool in neonates with neurological symptoms or suspected cerebral vascular abnormalities admitted to the neonatal intensive care unit.

Is a keystone Bone Anomaly the Main Cause of Flatfoot (Pes Planus)?

Flatfoot (pes planus) is a decrease or loss of longitudinal medial arch height. The cause of symptomatic flatfoot occurring in adolescents is still unclear. In this study, the relationship between adolescent pes planus and foot bone shape was investigated. For this purpose, the volume and superficial area data of the foot bones of adolescent individuals with flatfoot deformity and individuals without any foot deformity were compared. Between September 2022 and June 2023, 30 individuals with adolescent pes planus with a medial arch angle greater than 145 degrees and 30 individuals without any foot deformity were included in the study. Computed tomography (CT) images of the participants' feet were obtained with a General Electric brand IQ model 32 detector CT device with a section thickness of 0.625mm in accordance with the bone protocol. Using the 3D Slicer program on CT images, foot bones were segmented and the volume and surface area ratios of each foot bone were determined. Cuneiforme mediale and cuneiforme intermediale volume ratios in individuals with flatfoot deformity decreased by 14% and 24%, respectively, compared with the control group ( P <0.05). Cuneiforme mediale and cuneiforme intermediale superficial area ratios were found to be 10% and 30% lower in the flatfoot group compared with the control group, respectively ( P <0.05). There was no difference in the volume and superficial area ratios of other foot bones between the groups ( P >0.05). The study results suggest that symptomatic adolescent flatfoot deformity may be associated with developmental anomalies of the os cuneiforme mediale and os cuneiforme intermedium.

Use of CRISPRoff and synthetic Notch to modulate and relay endogenous gene expression programs in engineered cells.

Uncovering the stimulus-response histories that give rise to cell fates and behaviors is an area of great interest in developmental biology, tissue engineering, and regenerative medicine. A comprehensive accounting of cell experiences that lead to the development of organs and tissues can help us to understand developmental anomalies that may underly disease. Perhaps more provocatively, such a record can also reveal clues as to how to drive cell collective decision-making processes, which may yield predictable cell-based therapies or facilitate production of tissue substitutes for transplantation or in vitro screening of prospective therapies to mitigate disease. Toward this end, various methods have been applied to molecularly trace developmental trajectories and record interaction histories of cells. Typical methods involve artificial gene circuits based on recombinases that activate a suite of fluorescent reporters or CRISPR-Cas9 genome writing technologies whose nucleic acid-based record keeping serves to chronicle cell-cell interactions or past exposure to stimuli of interests. Exciting expansions of the synthetic biology toolkit with artificial receptors that permit establishment of defined input-to-output linkages of cell decision-making processes opens the door to not only record cell-cell interactions, but to also potentiate directed manipulation of the outcomes of such interactions via regulation of carefully selected transgenes. Here, we combine CRISPR-based strategies to genetically and epigenetically manipulate cells to express components of the synthetic Notch receptor platform, a widely used artificial cell signaling module. Our approach gives rise to the ability to conditionally record interactions between human cells, where the record of engagement depends on expression of a state-specific marker of a subset of cells in a population. Further, such signal-competent interactions can be used to direct differentiation of human embryonic stem cells toward pre-selected fates based on assigned synNotch outputs. We also implemented CRISPR-based manipulation of native gene expression profiles to bias outcomes of cell engagement histories in a targeted manner. Thus, we present a useful strategy that gives rise to both state-specific recording of cell-cell interactions as well as methods to intentionally influence products of such cell-cell exchanges.

Oral lesions and impacted teeth interlinked?-A review

Oral lesions are most prevalent in oral cavity. These have many etiologic factors. One of the most important being impacted teeth. These unerupted teeth become hazards both for patient and dentist. Also some lesions are connected with these developmental tooth anomalies. These have to be dealt seriously as if ignored they can transform into bigger oral pathologies that can be life threatening. This article sheds light onto these factors an attempt is made to highlighten these lesions that if diagnosed earlier, can be helpful in treatment planning clinically.

Dens in dente: A review of literature with a rare case report

Dens invaginatus (DI) (dens in dente) is a developmental anomaly resulting from an invagination in part of variable depth of the enamel organ into the dental papilla in the surface of the crown before calcification of the dental tissues. They are a target for caries leading to pulp necrosis and apical pathosis, so the diagnosis and early prevention measures are important. When treatment is necessary, conservative, endodontic, and periodontal possibilities are very effective. Surgical interventions are only rarely indicated. This article presents a unique case report of unilateral DI of Type III (Ohlers) involving the maxillary left central incisor as well as a comprehensive review of literature on history, aetiology and classification. Early detection and management are recommended before the development of pulpal and periodontal pathosis that further complicates the prognosis. Postoperative follow-up subsequent to treatment is essential for effective long-term clinical management.

Human Organoids for Rapid Validation of Gene Variants Linked to Cochlear Malformations.

Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital deafness. Most patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families. We subsequently generated monoclonal induced pluripotent stem cell (iPSC) lines, bearing patient-specific knockins and knockouts using CRISPR/Cas9 to assess pathogenicity of candidate variants. We detected FGF3 (p.Arg165Gly) and GREB1L (p.Cys186Arg), variants of uncertain significance in two recognized genes for deafness, and PBXIP1(p.Trp574*) in a candidate gene. Upon differentiation of iPSCs towards inner ear organoids, we observed significant developmental aberrations in knockout lines compared to their isogenic controls. Patient-specific single nucleotide variants (SNVs) showed similar abnormalities as the knockout lines, functionally supporting their causality in the observed phenotype. Therefore, we present human inner ear organoids as a tool to rapidly validate the pathogenicity of DNA variants associated with cochlear malformations.

Fronto-Orbital Advancement Using Computer-Aided Surgical Simulation: 2-Dimensional Operative Video

Craniosynostosis is a developmental anomaly resulting from the premature fusion of cranial sutures, with an estimated incidence of 1 per 2000 to 1 per 2500 births. 1 Surgical options for correction include open calvarial vault reconstruction, and more recently, endoscopic-assisted repairs that have been introduced to mitigate blood loss and hospital stay, 2 although these remain understudied. In this operative video (Video), the authors present the case of an 11-month-old girl with right-sided coronal craniosynostosis that was treated with coronal cranial vault reconstruction with fronto-orbital advancement using computer-aided surgical simulation (KLS Martin Group), which has been studied previously with acceptable results when comparing the preoperative plan to the postoperative outcome. 3 The patient was seen in follow-up at 1 month and 6 months and remained neurologically intact, continuing to meet all her developmental milestones appropriately. The patient's guardians consented to performance of the procedure and publication of the images. Institutional review board approval was deemed unnecessary. The participants and any identifiable individuals consented to publication of his/her images.

WPA1 encodes a vWA domain protein that regulates wheat plant architecture

Plant height, spike, leaf, stem and grain morphologies are key components of plant architecture and related to wheat yield. A wheat (Triticum aestivum L.) mutant, wpa1, displaying temperature-dependent pleiotropic developmental anomalies, was isolated. The WPA1 gene, encoding a von Willebrand factor type A (vWA) domain protein, was located on chromosome arm 7DS and isolated by map-based cloning. The functionality of WPA1 was validated by multiple independent EMS-induced mutants and gene editing. Phylogenetic analysis revealed that WPA1 is monocotyledon-specific in higher plants. The identification of WPA1 provides opportunity to study the temperature regulated wheat development and grain yield.

Preconceptional paternal obesity may increase the risk of congenital urogenital anomalies in offspring: A case-control study.

Congenital urogenital anomalies affect 4-60 per 10,000 births. Maternal obesity, along with other risk factors, is well documented as a contributing factor. However, the impact of paternal obesity on risk is unclear. Obesity is prevalent among men of reproductive age, highlighting the need for further research into the potential association between paternal obesity and offspring congenital urogenital anomalies. This study aims to determine the association between paternal obesity and the risk of congenital urogenital malformations in offspring. Case-control study conducted on 179 newborns (91 cases, 88 controls) selected from the Notre Dame des Secours-university hospital database. Cases were identified as newborns presenting at least one congenital urogenital abnormality, defined as developmental anomalies that can result in a variety of malformations affecting the kidneys, ureters, bladder, and urethra. Controls were identified as newborns without any congenital abnormalities. The exclusion criteria were maternal obesity, infections during pregnancy, chronic diseases, prematurity, growth retardation, assisted reproductive technologies for conception, substance abuse, down syndrome, and other malformations. Data were collected through phone interviews, medical records, and questionnaires. In this study, the exposure was the preconceptional paternal body mass index (BMI), which was calculated based on self-reported height and weight. According to guidelines from the US Centers for Disease Control and Prevention (CDC), individuals are considered to be in the healthy weight range if their BMI (kg/m2) is between 18.5 and<25. They are classified as overweight if their BMI is ≥ 25, obese class I if their BMI is between 30 and<35, obese class II if their BMI is between 35 and<40, and obese class III if their BMI is 40 or higher. Logistic regression analysis was employed to quantify the association between paternal obesity and urogenital conditions in offspring. Significant differences in median (minimum-maximum) paternal BMI values were noted between the cases and controls at the time of conception (cases: 27.7 (43-20.1), controls: 24.8 (40.7-19.6); p<0.0001). Logistic regression analysis confirmed that at the time of conception, compared to normal-weight fathers, overweight fathers displayed a heightened risk of offspring congenital malformations, with an odds ratio (OR) of 4.44 (95% CI=2.1-9.1). Similarly, fathers categorized as obese Class I at conception had approximately eight times higher odds (OR=8.62, 95% CI=2.91-25.52) of having offspring with urogenital conditions compared to normal-weight fathers. Additionally, fathers classified as obese Class II at conception exhibited 5.75 times higher odds (OR=5.75, 95% CI=0.96-34.44) of having offspring with urogenital conditions in comparison to normal-weight fathers. We found that the risk of urogenital malformations increased with paternal BMI during the preconceptional period. The findings suggest the importance of addressing paternal obesity in efforts to reduce the risk of urogenital congenital malformations in offspring.

Treatment outcomes in maxillofacial rehabilitation: a scoping review protocol.

The objective of this scoping review is to assess the treatment outcomes following maxillofacial rehabilitation and to identify the tools used to evaluate those outcomes. Maxillofacial defects caused due to tumor, trauma, or any pathology affects the patient physically, mentally, and psychologically. Various methodologies and strategies are used for jaw reconstruction and oral rehabilitation to help the patient regain the functions and quality of life that were lost due to the defect. The evaluation of these treatment outcomes is imperative to assess the success of rehabilitation. The review will include patients with any maxillofacial defect caused by a developmental anomaly, trauma, or tumor. The patients must have undergone any type of reconstruction and/or rehabilitation and can be from any age group. All treatment outcomes of maxillofacial rehabilitation will be considered. Information from primary and secondary sources and from diverse geographical settings will be included. This review will follow the JBI methodology for scoping reviews. Databases to be searched will include PubMed (Ovid), Scopus, PsycINFO (EBSCOhost), CINAHL(EBSCO), Web of Science, Cochrane CENTRAL, ProQuest Dissertations and Theses, and Google Scholar (first 10 pages of the search). Two independent reviewers will screen the titles and abstracts and extract data from selected studies. Data will be presented in tabular format, accompanied by a narrative summary. https://doi.org/10.17605/OSF.IO/DP8WC.

Dens invaginatus: a review of its aetiology, diagnosis and clinical management

Dens invaginatus is a developmental anomaly predominantly occurring in maxillary lateral incisors, resulting in the invagination of the enamel into the dentine. This infolded area creates a void enabling the stagnation of bacteria and development of dental caries. If left untreated the caries may progress and ultimately result in pulpal necrosis. The treatment of these teeth can be challenging due to the potential complexity of the lesion. It is essential that teeth with dens invaginatus are diagnosed early allowing prophylactic treatment and prevention of pulpal necrosis. This article aims to review the aetiology, prevalence, classification, diagnosis, treatment and orthodontic considerations of teeth affected by dens invaginatus. CPD/Clinical Relevance: Knowledge of dens invaginatus enables early diagnosis, effective management and, therefore, the best treatment outcomes.

Catalogue of stuffed birds with atypical colouration and developmental anomalies deposited in the State Museum of Natural History NASU, Lviv, Ukraine

Birds with atypical colouration and developmental anomalies very rarely occur in the wild, and museum collections of such specimens have been formed over centuries. Today, their scientific importance is growing due to the emergence of new opportunities in genetic research, and distribution of information on the collections of this kind is a useful thing. The digitization of collections becomes especially important in times of war, because currently none of the museum collections in Ukraine have guarantees against possible losses. The collection of stuffed birds with atypical colouration and developmental anomalies, deposited in the State Museum of Natural History, NASU includes 157 specimens of 44 species. It was collected from 1850 to 1930. Later, only one stuffed bird was received in 2012. The collection was formed both as a result of the activities of museum staff (hunting, buying at markets) and the receipt of numerous gifts to the museum's founder, Volodymyr Didushytskyi. Among the species, the most numerous are the house sparrow Passer domesticus L., 1758 – 24 spec., the grey crow Corvus cornix L., 1758, the rook Corvus frugilegus L., 1758 and the village swallow Hirundo rustica L., 1758, presented by 11 spec. each, and the grey partridge Perdix perdix L., 1758 – 9 spec. Some 117 specimens were collected from the present territory of Ukraine, 28 spec. from the present territory of Poland, and the place of collection of the remaining 12 specimens is unknown. In Ukraine, most specimens were collected in Lvivska province (89); the rest – in Ternopilska province (15), Ivano-Frankivska province (12) and Volynska province (1). In Poland, 12 specimens were collected in the Podkarpackie voivodeship, 11 spec. in the Małopolskie voivodeship, 2 spec. in the Lubelskie voivodeship and 1 spec. in the Lódzkie voivodeship. Among all localities, the largest number of specimens was collected from Lviv City and its environs – 24, form the village of Peniaky, Zolochivskyi district, Lvivska province – 12, and from Kraków City and its environs – 11. At the end of 2023, the entire collection was digitized as a part of the project "Crisis Inventory and Leap to Digitalization of Museum Records" Tustan NGO, “Tustan” State Historical and Cultural Museum, NeMo: Ukrainian Heritage Monitoring Lab and the NGO “Centre for Museum Development” with the financial support of the European Union. Each exhibit was photographed in six projections: front, left and right sides, back, bottom, and in the most favourable exhibition position. The catalogue was prepared within the framework of the project "Methodological principles of expert evaluation of the scientific potential of natural history collections" of the Department of Applied Museology of the State Museum of Natural History, National Academy of Sciences of Ukraine, state registration No.0122U001440.

Exploring Genetic Variants in Ellis-Van Creveld Syndrome: Insights from a Consanguineous Family

Background: Ellis-Van Creveld Syndrome (EVC) is a rare genetic disorder characterized by skeletal abnormalities and developmental anomalies, presenting significant challenges in diagnosis and understanding its genetic underpinnings. Objective: This study aimed to comprehensively investigate the clinical and molecular aspects of EVC within a consanguineous family from Pakistan, identifying the genetic variants involved. Methods: A detailed clinical assessment was conducted on all family members, documenting phenotypic features such as polydactyly, syndactyly, dental abnormalities, and short stature. Pedigrees were constructed following established guidelines to depict familial relationships and inheritance patterns. Venous blood samples were collected for genomic DNA extraction using the Phenol-Chloroform Method. Microsatellite marker analysis was performed for linkage mapping, guided by the UCSC Genome Browser and Rutgers Combined Linkage-Physical Map. Mutation screening of the EVC and EVC2 genes was conducted using Sanger sequencing, with primers designed targeting exon-intron boundaries and coding exons. PCR amplification and sequencing were performed according to standard protocols. Data analysis was carried out using SPSS version 25. Results: Clinical assessment revealed classical EVC phenotypes, including bilateral postaxial polydactyly in 80% of affected individuals and dental abnormalities in 70%. Microsatellite marker analysis identified linkage to the EVC/EVC2 locus on chromosome 4p16.2. However, Sanger sequencing of the 21 coding exons of EVC and the 22 exons of EVC2 did not detect any pathogenic mutations. Haplotype analysis confirmed the segregation of specific markers with affected individuals, suggesting the involvement of additional genetic factors. Conclusion: The study's findings challenge the traditional understanding of EVC, highlighting the necessity for advanced genomic techniques such as whole-genome sequencing to fully elucidate its genetic contributors. These insights underscore the heterogeneous nature of EVC and emphasize the importance of comprehensive genetic screening for accurate diagnosis and personalized management of this rare genetic disorder.

Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study

BackgroundCerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The...

Unilateral optic nerve aplasia associated with microphthalmia: a rare cadaveric report

This case report describes the anatomical presentation of the anomalous optic nerve (cranial nerve II). Cranial nerve II developmental anomalies encompass both optic nerve hypoplasia and aplasia. While most studies on optic nerve anomalies rely on radiological imaging, anatomical presentation and nerve course are rarely described. The current case reveals a complete absence of the right optic nerve and its connection to the optic chiasma, resembling radiological presentation of optic nerve aplasia. In addition, the right-sided bony orbit and eyeball were smaller than the left, accompanied by a poorly developed cornea and iris with a calcified mass, resembling clinical presentation of microphthalmia. Having a thorough understanding of the gross anatomical presentation and course of optic nerve anomalies can facilitate precise diagnosis and management of visual impairments associated with these anomalies. Furthermore, such knowledge can provide valuable insights into the actual prevalence of optic nerve aplasia and further substantiate the literature.

Imaging features, classification and clinical features of intrahepatic congenital portosystemic shunts.

Congenital portosystemic shunts (CPSS) are a rare developmental anomaly diverting blood flow from the portal venous system and the liver to the systemic venous system. This case series examines the sonographic imaging findings, shunt classification, ultrasound shunt ratios, and outcomes in nine children (5 females, 4 males) admitted to our institution between 2015 and 2022 were included in this study. The shunts were initially categorized by the Parks classification and were followed by serial ultrasounds. Clinical presentation, clinical course, laboratory data, shunt ratios, and time to shunt closure were all followed on subsequent ultrasounds. The most common type of CPPS was the Type 3 shunt. In cases where shunt ratios were measured, the shunt ratio gradually decreased in tandem with decreasing ammonia levels until spontaneous closure was achieved. Predictors of lack of shunt closure included high shunt ratios and Type 4 shunts. Patients with CPPS can be followed with the shunt ratio calculation obtained from sonographic imaging, which may correlate to ammonia levels and indicate risk of hepatic encephalopathy as well as predict speed and timing of closure.

Forensically Valuable Odonatological Records Documentation in an Era of Electronics: How Aware Are the Dental Fraternity?

Forensic odontology plays a pivotal role in the identification of victims in mass disasters with the help of "Preserved dental records" available to general dental practitioners (GDPs). Comparison of dental data obtained from the deceased person with dental data obtained by the dentist from the person's file is a primary method of identification through dental evidence. We explored the practice of maintaining dental records among GDPs, as well as their knowledge of legal regulations and the application of dental records in forensic odontology. Two hundred fifty dentists participated in an online survey. Questions covered general information on dentists, maintenance of dental records, and knowledge of legal requirements and forensic odontology. Overall, 85.2% of dentists obtain and archive written informed consent, while 73.2% retain records in the form of dental cast. Generally, non-carious dental lesions and developmental dental anomalies were not recorded. About 90.8% of dentists use Fédération Dentaire Internationale (FDI) notation. The survey revealed different practices in the maintenance of dental records, including significant flaws and a lack of awareness of their forensic importance. This obvious need for additional education on the proper maintenance of dental records could be met by including forensic odontology in compulsory undergraduate courses and postgraduate dental education. Establishing national and international standards in dental charting would comply with contemporary trends in health care and the requirements of forensic expertise.