Forebrain commissure formation in zebrafish embryo requires the binding of KLC1 to CRMP2.

Formation of the corpus callosum (CC), anterior commissure (AC), and postoptic commissure (POC), connecting the left and right cerebral hemispheres, is crucial for cerebral functioning. Collapsin response mediator protein 2 (CRMP2) has been suggested to be associated with the mechanisms governing this formation, based on knockout studies in mice and knockdown/knockout studies in zebrafish. Previously, we reported two cases of non-synonymous CRMP2 variants with S14R and R565C substitutions. Among the, the R565C substitution (p.R565C) was caused by the novel CRMP2 mutation c.1693C > T, and the patient presented with intellectual disability accompanied by CC hypoplasia. In this study, we demonstrate that crmp2 mRNA could rescue AC and POC formation in crmp2-knockdown zebrafish, whereas the mRNA with the R566C mutation could not. Zebrafish CRMP2 R566C corresponds to human CRMP2 R565C. Further experiments with transfected cultured cells indicated that CRMP2 with the R566C mutation could not bind to kinesin light chain 1 (KLC1). Knockdown of klc1a in zebrafish resulted in defective AC and POC formation, revealing a genetic interaction with crmp2. These findings suggest that the CRMP2 R566C mutant fails to bind to KLC1, preventing axonal elongation and leading to defective AC and POC formation in zebrafish and CC formation defects in humans. Our study highlights the importance of the interaction between CRMP2 and KLC1 in the formation of the forebrain commissures, revealing a novel mechanism associated with CRMP2 mutations underlying human neurodevelopmental abnormalities.

Novel STAR Gene Variant of Congenital Lipoid Adrenal Hyperplasia With Testicular Adrenal Rests.

A mutation in the steroidogenic acute regulatory protein (STAR) gene, which encodes a protein that plays a crucial role in steroid hormone synthesis, causes a severe form of congenital adrenal hyperplasia (CAH) known as lipoid CAH (LCAH). LCAH presents with primary adrenal insufficiency (PAI) as well as atypical genitalia. Individuals with LCAH require adrenal steroid hormone supplements for survival. Masculinization in males with STAR deficiency varies from incomplete to normal virilization. Radiological examinations reveal enlarged and lipid-laden adrenals. A 10-year-old boy born of second-degree consanguinity presented with weight gain and hyperpigmentation for 1 year. He was diagnosed with PAI at age 7 months and treated with hydrocortisone and fludrocortisone. Dynamic adrenal gland testing revealed undetectable hormone reserves. Imaging detected hypoplastic adrenals and a small testis with testicular adrenal rests (TART). Genetic analysis indicated a novel homozygous pathogenic variant of STAR in exon 7, c.814C > G(pArg272Gly) associated with LCAH (OMIM No. 201710). Testing revealed that asymptomatic family members and relatives were heterozygotes for the variant. The patient was diagnosed with nonclassic LCAH with hypoplastic adrenals and TART. Adequate hormone supplementation resulted in TART regression. This genetic variation is reported for the first time.

Prenatal diagnosis of cleidocranial dysplasia: Case report on two cases with a negative family history.

Introduction: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia that presents with abnormalities in the craniofacial region, teeth, and clavicles and is linked to RUNX2 mutation. Prenatal diagnoses of CCD have rarely been reported, and most of these cases have a positive family history. Here we report two prenatally diagnosed CCD cases without a positive family history. We conducted a literature review to summarize the prenatal sonographic findings of CCD. Case reports: Case 1 (a 26-year-old woman): ultrasound at 13 weeks showed a thickened nuchal translucency with absent nasal bones and poor ossifications in the cranium and vertebrae. Genetic testing confirmed a frame shift deletion of RUNX2. Case 2 (a 27-year-old woman): ultrasound at 32 weeks showed potential fetal skeletal dysplasia, with inadequate skull ossification, mild ossified bilateral clavicles, and RUNX2 frameshift deletion mutation. Both cases were diagnosed with CCD and the parents chose pregnancy termination. Conclusion: These cases underscore the importance of sonographic examination for prenatal CCD diagnosis with a negative family history. By reviewing previous cases, we concluded that combining NB hypoplasia, clavicle and skull hypoplasia, and shortened long bones may be effective for early screening for CCD. Prenatal diagnosis is crucial for guiding medical decisions.

Vitamin D deficiency and chronological hypoplasia with hypomineralisation: a case report.

Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and dental evaluations of a child with VDD, referred to the dental office. A 10-year-old British Asian boy was referred to the paediatric specialist dentistry clinic by the general dentist for dental management. The medical history depicted that the patient was diagnosed with VDD, secondary hyperparathyroidism and delayed growth. Moreover, his mother had the VDD during pregnancy. The patient was breast fed and had rickets in infancy. He was prescribed vitamin D supplements at the age of 16 months. He had received multiple dental treatments under local anaesthesia but with limited cooperation. Clinical examination revealed that the patient had chronological enamel hypoplasia shown as bands at the occlusal third on specific teeth. Suboptimal hygiene with general plaque induced gingivitis, dental caries in permanent and primary teeth, and delayed the teeth eruption. Preventions included appropriate oral hygiene and dietary advice, fluoride varnish application and fissure sealant placement. The treatments included anterior direct composite restoration, posterior composite restoration, stainless steel crowns and extractions. Thorough medical history is essential to understand the underlying causes of dental defects. Early dental intervention can restore the patient appearance and function and prevent further dental damage.

Anatomy of vertebral artery hypoplasia and its relationship with clinical implications: a systematic review and meta-analysis of prevalence.

PURPOSE: The vertebral artery (VA) is a vital branch of the subclavian artery, coursing through the transverse foramina of the cervical vertebrae, and playing a crucial role in irrigating the posterior region of the arterial cerebral circle, also known as the Polygon of Willis. Among the various possible alterations that can affect the VA, vertebral artery hypoplasia (HAV) emerges as a significant variant. This study aims to discern the anatomical features of HAV and its correlation with the clinical conditions of the posterior cerebral circulation. METHODS: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were searched until January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. RESULTS: A total of 24 studies met the established selection criteria, with a total of 8847 subjects. In this study, 6 articles were included for the meta-analysis with a total of subjects. The average prevalence of VAH reported in each study was 11% (95% CI 10-12%); the studies had a heterogeneity of 41% based on the funnel plot and a low risk of bias. CONCLUSION: The prevalence of VAH is low, but in the presence of this condition, the changes are mainly in diameter rather than morphological. If it is present, some clinical safeguards must be taken to avoid complications such as stroke.

Poland syndrome combined with breast cancer: a case report.

Background: Poland syndrome is an occasional congenital malformation characterized by unilateral chest wall dysplasia and ipsilateral upper limb abnormalities. An association between Poland syndrome and breast cancer has been reported, but no clear etiological link between Poland syndrome and breast tumors has been established. We report a case of Poland syndrome combined with breast cancer and analyzed the clinical features of breast cancer in this case and its influence on the choice of treatment for breast cancer. Case Description: In February 2022, we admitted a 47-year-old woman with Poland syndrome involving the right limb combined with right-sided breast cancer. After admission, the patient was given eight cycles of neoadjuvant therapy and underwent a modified radical mastectomy on September 7, 2022. Absence of right pectoralis major muscle and pectoralis minor muscle, thoracic deformity, and an adhesive band along the side of the sternum to the right axilla were observed during the operation. After surgery, the incision achieved grade-A healing, and the targeted therapy was continued for 1 year. The patient was followed up for 8 months after surgery, and the limb function of the affected side recovered well, and no obvious subcutaneous effusion, flap necrosis, upper limb edema, and other complications were observed. Conclusions: The anatomic variation of patients with Poland syndrome has some influence on the selection of surgical methods for breast cancer, but whether it would affect the prognosis of patients is unknown. To clarify the relationship between Poland syndrome and breast cancer, we need more cases to conduct etiological studies in the future.

Geometry and Symmetry of Willis' Circle and Middle Cerebral Artery Aneurysms Development.

Background: A relationship between the geometry and symmetry of Willis' circle and intracranial aneurysms was reported for anterior communicating and posterior communicating (PCom) aneurysms. A similar association with the middle cerebral artery (MCA) aneurysms instead appeared weaker. Methods: We reviewed 432 patients from six Italian centers with unilateral MCA aneurysms, analyzing the relationship between the caliber and symmetry of Willis' circle and the presence of ruptured and unruptured presentation. CT-angiograms were evaluated to assess Willis' circle geometrical characteristics and the MCA aneurysm side, dimension and rupture status. Results: The hypoplasia of the first segment of the anterior cerebral artery (A1) was in approximately one-quarter of patients and PCom hypoplasia was in almost 40%. About 9% had a fetal PCom ipsilaterally to the aneurysm. By comparing the aneurysmal and healthy sides, only the PCom hypoplasia appeared significantly higher in the affected side. Finally, the caliber of the internal carotid artery (ICA) and the first segment of MCA (M1) caliber were significantly greater in patients with unruptured aneurysms, and PCom hypoplasia appeared related to the incidence of an ipsilateral MCA aneurysm and its risk of rupture. Conclusions: Although according to these findings asymmetries of Willis' circle are shown to be a risk factor for MCA aneurysm formation and rupture, the indifferent association with ipsilateral or contralateral hypoplasia remains a datum of difficult hemodynamic interpretation, thereby raising the concern that this association may be more casual than causal.

Full-Mouth Rehabilitation of a 15-Year-Old Girl Affected by a Rare Hypoparathyroidism (Glial Cell Missing Homolog 2 Mutation): A 3-Year Follow-Up.

OBJECTIVE: Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The resulting hypocalcemia may lead to dental abnormalities, such as enamel hypoplasia. The aim of this paper was to describe the full-mouth rehabilitation of a 15-year-old girl with chronic hypocalcemia due to a rare congenital hypoparathyroidism. CLINICAL CONSIDERATIONS: In this patient, in the young adult dentition, conservative care was preferred. Onlays or stainless-steel crowns were performed on the posterior teeth, and direct or indirect (overlays and veneerlays) were performed on the maxillary premolars, canines, and incisors, using a digital wax-up. The mandibular incisors were bleached. The treatment clearly improved the patient's oral quality of life, with fewer sensitivities, better chewing, and aesthetic satisfaction. The difficulties were the regular monitoring and the limited compliance of the patient. CONCLUSION: Despite no clinical feedback in the literature, generalized hypomineralized/hypoplastic teeth due to hypoparathyroidism in a young patient can be treated as amelogenesis imperfecta (generalized enamel defects) with a conservative approach for medium-term satisfactory results. HIGHLIGHTS: This study provides new insights into the management of enamel hypoplasia caused by familial isolated hypoparathyroidism, helping to improve patient outcomes in similar cases.

Dental anomalies in craniofacial microsomia and condylo-mandibular dysplasia: A retrospective study of 103 patients.

INTRODUCTION: Craniofacial microsomia (CFM) and camel-hump condylo-mandibular dysplasia (CMD) are developmental disorders affecting the mandible that share common clinical features. This study aimed to investigate and compare the dental anomalies (DA) between the two entities for differential diagnosis and to propose appropriate treatment. METHODS: This retrospective cross-sectional study was based on panoramic radiographs of patients diagnosed with CFM or CMD. DA were evaluated using the classification reported by Bilge. Delayed tooth eruption on the affected side was noted based on a comparison with the contralateral side. Nolla's stages of tooth calcification were used to assess dental development. RESULTS: A total of 103 patients were included, 80 subjects (77.7 %) in CFM group and 23 patients (22.3 %) in CMD group. The prevalence of DA among CFM and CMD-affected patients were 80.0 % and 95.7 %, respectively. Tooth ectopia, tooth impaction, dental development delay, and delayed tooth eruption on the affected side exhibited a significant association with the two craniofacial malformations. The overall affected teeth (molars, premolars, canines) differed between the two craniofacial malformations. Dental abnormalities such as oligodontia, hyperdontia, dentin dysplasia, and anomalies of shape were seen only in subjects affected by CFM. CONCLUSION: DA were widely observed in patients with CFM and CMD. The global distribution of affected teeth differed between the two conditions and some DA were detected only in CFM patients. When clinical diagnosis remains uncertain, some specific radiological characteristics of DA can be used to differentiate CFM from CMD.

Lung Underdevelopment: Case Reports and a Literature Review.

Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations. LEARNING POINTS: Pulmonary underdevelopment is a challenging diagnosis and should be considered in patients with unilateral opacification on chest radiograph.Childhood developmental history is critical for diagnosis as delayed, or misdiagnoses are common. Definitive diagnosis can be made by computed tomography scan.Management is watchful waiting with close monitoring, with long term prognosis remaining unclear.

Imaging spectrum of horseshoe lung: A series of four cases.

Horseshoe lung (HL) is a rare congenital anomaly represented by the fusion of both lungs, posterior to the heart, and is typically associated with various bronchopulmonary and cardiovascular malformations. Multi-detector contrast enhanced CT is the imaging modality of choice to demonstrate the pathology and associated malformations. There has been inconsistency in the nomenclature used for such cases in literature. To resolve ambiguity, the authors emphasise that only two terms: HL and pseudo-HL be used on imaging to describe variants of this congenital malformation. Contribution: A description of the imaging features in four cases of HL, with their associated malformations and a review of the nomenclature.

Vertebral artery hypoplasia and hemodynamic impairment in transient global amnesia: a case control study.

Introduction: The aetiology of transient global amnesia (TGA) is still a matter of debate. Besides ischemia of the mesial temporal lobe including the hippocampus, migraine-like mechanisms, epileptic seizures affecting mnestic structures, or venous congestion in the (para) hippocampal area due to jugular vein insufficiency have been discussed. We assessed the diameters of the intracranial arteries of TGA patients compared to controls to identify differences that support the hypothesis of reduced hippocampal perfusion as a pivotal factor in the pathophysiology of TGA. Methods: We reviewed magnetic resonance imaging time of flight angiographies (TOF-MRA) that were acquired during in-patient treatment of 206 patients with acute TGA. Results: The diameters of the vertebral artery (VA) in the V4 segment, the proximal basilar artery, and the internal carotid arteries were measured manually. We compared the findings with TOF-MRA images of an age and sex matched control group of neurological patients without known cerebrovascular pathology. In TGA patients the diameter of the right VA was significantly (p < 0.01) smaller compared to controls (2.09 mm vs. 2.35 mm). There were no significant differences in the diameters of the other vessels. Only the fetal variant of the posterior cerebral artery was slightly more common in TGA. Discussion: The smaller diameter (hypoplasia) of the right VA supports the hypothesis of a contribution of hemodynamic factors to the pathophysiology of TGA. The fact that hypoplasia represents a congenital condition might be the explanation why previous studies failed to find an increased rate of the classical (acquired) vascular risk factors.

Characteristic deviations of the optic disc and macula in optic nerve hypoplasia based on OCT.

PURPOSE: The purpose of this study was to evaluate the optic disc and macula in a large cohort of patients with different severity of optic nerve hypoplasia (ONH) using high-resolution spectral domain optical coherence tomography (SD-OCT). METHODS: In total, 36 patients (52 ONH eyes and 17 fellow eyes in unilateral cases) and 45 healthy right eyes from 45 controls were evaluated. All patients underwent an examination to confirm the diagnosis. SD-OCT images of the disc and macula were obtained and analysed both quantitatively and qualitatively. RESULTS: OCT in ONH eyes demonstrated a shorter disc diameter (1061 ± 375 µm vs. 1751 ± 221 µm, p < 0.001), shallower mean cup depth (427 ± 171 µm vs. 551 ± 152 µm, p = 0.01), thinner ganglion cell complex (GCC) perifoveally (47.3 ± 13.0 µm, 60.8 ± 6.0 µm, p < 0.001) and reduced foveal depth (61 ± 36 µm, 119 ± 19 µm, p < 0.001) compared to control eyes. Qualitative analysis showed that 1/3rd of ONH eyes lacked signs of an optic cup, and 2/3rd had reduced or no sign of a foveal pit. Fellow eyes had shorter disc diameter (1446 ± 404 µm vs. 1751 ± 221 µm, p = 0.004) and reduced foveal depth (93 ± 27 µm vs. 119 ± 19 µm, p < 0.001) but similar GCC thickness (60.8 ± 7.1 µm vs. 60.8 ± 6.0 µm, p = 0.738) compared to controls. Disc diameter showed the best correlation with visual acuity in ONH eyes (ρ = 0.517, p < 0.001). CONCLUSION: ONH eyes have reduced GCC thickness and reduced or no foveal pit. Fellow eyes in presumed unilateral cases have a smaller disc diameter and reduced foveal depth compared to controls, suggesting the possibility of subclinical/mild disease. However, GCC thickness was normal. The correlation between structure and visual function is not always straightforward.

Gastroschisis and septo-optic-pituitary dysplasia: Is there an association?

AIM: There are several case reports describing patients with both optic nerve hypoplasia/septo-optic-pituitary dysplasia (ONH/SOD) and gastroschisis (GS). Our aim was to investigate whether ONH/SOD is associated with GS. METHODS: A retrospective population-based study was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada to investigate if any patient with ONH/SOD also had GS. In addition, Winnipeg's Surgical Database of Outcomes and Management (WiSDOM), a hospital-based paediatric surgical database, was searched to ascertain if any of the patients with GS also have ONH/SOD. RESULTS: Cases were 124 patients with ONH/SOD diagnosed during 1990-2019. None had GS. The surgical database had 188 patients from Manitoba with GS during 1991-2019. None had ONH/SOD. CONCLUSION: There does not appear to be an association between ONH/SOD and GS in our cohorts of patients with these two disorders.

Isolated Apical Hypoplasia of the Left and Right Ventricle.

Isolated apical ventricular hypoplasia is an extremely rare congenital heart disease. We describe 2 cases, each affecting a different side, presenting with unique clinical and imaging characteristics not hitherto delineated in the literature.

Renal Endometriosis Mimics Renal Cell Carcinoma in a Hypoplastic Kidney: A Case Report.

Renal endometriosis is a rare disorder of cases of urinary tract endometriosis. A 42-year-old woman presented at our outpatient department with an incidental painless mass on her left hypoplastic kidney revealed on an abdominal ultrasound. Abdominal and pelvic examinations revealed no abnormal findings. A computed tomography (CT) scan revealed an anterolateral slightly enhanced left renal mass that measured 1.2 cm in diameter. Furthermore, CT did not reveal any evidence of abdominal or thoracic metastasis. There are a few case reports in the literature of tumors in specimens from patients who underwent nephrectomy for hypoplastic kidneys, but discriminating between benign and malignant masses is difficult unless a nephrectomy is performed. Given the radiological findings and the impaired function of the hypoplastic kidney, laparoscopic radical nephrectomy was recommended. The procedure was performed under general anesthesia without intraoperative or postoperative complications. Microscopic examination revealed several findings consistent with a diagnosis of renal endometriosis. The patient had no symptoms at her last follow-up visit. This case highlights that renal endometriosis can mimic renal cell carcinoma and awareness of this entity should be raised, as it can be asymptomatic, especially when located in a hypoplastic kidney.

Stabilization of the hypoplastic thumb type Blauth IIIB using a non-vascularized proximal interphalangeal joint from the toe as an alternative reconstruction when pollicization is not accepted: Description of the surgical technique.

BACKGROUND: A Blauth IIIB hypoplastic thumb is a significant functional and cosmetic problem for the developing hand in children. The gold standard in treatment is amputation and index pollicization. Despite the good functional results, some parents do not consent to the operation, mainly for cosmetic reasons. OBJECTIVES: The aim is to present a detailed description and features of the technique used in our department for stabilization of a hypoplastic thumb type Blauth IIIB with a non-vascularized proximal interphalangeal joint from the toe. This is the first description of this surgery for this kind of congenital defect, together with the largest group of patients analyzed compared to alternative techniques described in the literature. MATERIAL AND METHODS: Sixteen patients were included in the analysis. The mean age was 3 years (standard deviation (SD) ±2). In most cases, it was a unilateral and isolated defect. We described the surgical technique and postoperative management in detail and assessed intraoperative factors such as donor selection, operative time, technical problems, stabilization time, complication rate, and reoperations. Appropriate statistics were performed. RESULTS: Most often, the graft was taken from the 3rd toe. The average operation time was 59 ±17.5 min. No technical problems were found during the surgery. The Kirschner wire was removed after an average of 6.5 weeks. The complication rate was 25%, which included the destabilization of Kirschner wires or graft non-union, but it decreased to 6% after reoperation. Five patients underwent tendon transfers. CONCLUSIONS: The presented technique is based on principles such as vascularized metatarsophalangeal joint transplants. It may be an option for stabilizing a hypoplastic thumb if parents do not consent to pollicization. Having microsurgical skills is unnecessary. The operation and anesthesia times are significantly shorter, resulting in less burden on the child's body. The study will continue assessing long-term postoperative functions and the comparison to pollicization.

Long-term follow-up for the atypical radial longitudinal deficiency: A case report.

We experienced an atypical case of radial longitudinal deficiency that did not fit into any classifications, including Blauth. The patient had a bilateral hypoplastic thumb, in which the index and middle fingers were missing in the right hand. We performed surgeries in four stages: centralization of the right hand, opponensplasty of the right thumb, opponensplasty of the left thumb, and distraction lengthening of the right ulnar. Twenty-five years after the initial treatment, the patient was satisfied with the treatment and had no significant difficulty with activities of daily living.

Bayesian modeling of spatially differentiated multivariate enamel defects of the children's primary maxillary central incisor teeth.

BACKGROUND: The analysis of dental caries has been a major focus of recent work on modeling dental defect data. While a dental caries focus is of major importance in dental research, the examination of developmental defects which could also contribute at an early stage of dental caries formation, is also of potential interest. This paper proposes a set of methods which address the appearance of different combinations of defects across different tooth regions. In our modeling we assess the linkages between tooth region development and both the type of defect and associations with etiological predictors of the defects which could be influential at different times during the tooth crown development. METHODS: We develop different hierarchical model formulations under the Bayesian paradigm to assess exposures during primary central incisor (PMCI) tooth development and PMCI defects. We evaluate the Bayesian hierarchical models under various simulation scenarios to compare their performance with both simulated dental defect data and real data from a motivating application. RESULTS: The proposed model provides inference on identifying a subset of etiological predictors of an individual defect accounting for the correlation between tooth regions and on identifying a subset of etiological predictors for the joint effect of defects. Furthermore, the model provides inference on the correlation between the regions of the teeth as well as between the joint effect of the developmental enamel defects and dental caries. Simulation results show that the proposed model consistently yields steady inferences in identifying etiological biomarkers associated with the outcome of localized developmental enamel defects and dental caries under varying simulation scenarios as deemed by small mean square error (MSE) when comparing the simulation results to real application results. CONCLUSION: We evaluate the proposed model under varying simulation scenarios to develop a model for multivariate dental defects and dental caries assuming a flexible covariance structure that can handle regional and joint effects. The proposed model shed new light on methods for capturing inclusive predictors in different multivariate joint models under the same covariance structure and provides a natural extension to a nested hierarchical model.