Normal Embryological Development Research Articles

At the Origin of Brain Malformations: Embryology of the Central and Peripheral Nervous System

AbstractDevelopment of the central nervous system is a time-ordered and multistepped process that begins in the third week of development and continues after birth. Understanding of its normal embryologic development is fundamental to understand how specific malformations develop. This article provides a summary of human brain development and serves as a base to introduce the various malformations presented in this issue.

Benign phyllodes tumor arising from accessory breast tissue of the axilla: An inquisitive rarity

Abstract Accessory breast tissue is the superfluous tissue that persists from normal embryological development. The pathological involvement of this tissue is quite uncommon and can be diagnostically challenging. Phyllodes tumor is a rare mammary fibroepithelial lesion that has been seldom reported to originate from the accessory breast tissue. This article describes an extremely rare case of a benign phyllodes tumor arising from the accessory breast tissue of the left axilla in a 40-year-old female so as to create awareness about rare tumors occurring within rare anomalies.

Imaging of Pediatric Ocular Globe Pathologies

The spectrum of ocular diseases encountered in the pediatric population is different from that in adults. Recognition of the normal embryologic development and anatomy is crucial to understand various ocular pathologies. Cross-sectional imaging supplements the clinical evaluation in establishing an accurate diagnosis, guiding management and monitoring diseases of the ocular globe. CT is mostly reserved for evaluation of acute processes in the setting of trauma or infection. MR imaging is the technique of choice for most other ocular conditions, given its high soft-tissue resolution. This article highlights the relevant embryologic developmental stages and normal anatomy and provides a review of various pediatric orbital pathologies and their key imaging features.Learning Objective: To recognize the normal embryologic development, anatomy, and key imaging features of common ocular pathologies in the pediatric population to aid the neuroradiologist in promptly detecting and confidently establishing the diagnosis of pediatric ocular disease

Imaging Features of Ectopic Tissues and Their Complications: Embryologic and Anatomic Approach

Ectopic tissue is an anatomic abnormality in which tissue develops in an area outside its normal location. It is primarily caused by abnormalities during the process of embryologic development. Although the majority of individuals with ectopic tissues remain asymptomatic, various symptoms and associated complications can occur. Failure in normal embryologic development leads to loss of normal physiologic function or may result in harmful functions such as ectopic hormonal secretion in the ectopic pituitary adenoma. Ectopic tissues may also frequently mimic tumors. For example, developmental abnormalities in the pharyngeal pouches may result in an ectopic parathyroid gland and ectopic thymus, both of which are frequently misdiagnosed as tumors. Adequate knowledge of embryology is essential for understanding the differential diagnoses of ectopic tissues and facilitating appropriate management. The authors summarize the embryologic development and pathogenesis of ectopic tissues by using illustrations to facilitate a deeper understanding of embryologic development and anatomy. Characteristic imaging findings (US, CT, MRI, and scintigraphy) are described for ectopic tissues of the brain, head, neck, thorax, abdomen, and pelvis by focusing on common conditions that radiologists may encounter in daily practice and their differential diagnoses. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

The Effect of Huntington's Disease on the Basal Nuclei: A Review.

Huntington’s disease is an autosomal dominant trinucleotide repeat disorder that causes the progressive degeneration of the basal nuclei. This degeneration leads to clinical symptoms affecting voluntary movement, cognitive impairment, and psychiatric disorders. The patient affected by this disease demonstrates anticipation, meaning that even though there is normal embryological development, the signs and symptoms appear at an earlier age as the gene is continually passed throughout subsequent generations. The degeneration occurs due to the accumulation of the protein Huntingtin that destroys the medium spiny neurons located in the caudate and putamen, collectively termed the striatum. Four pathways converge onto the striatum known as the “input” center. These consist of the motor loop, oculomotor loop, association loop, and limbic loop. In each of these loops, the striatum maintains an inhibitory gamma-aminobutyric acid (GABA)-ergic function. The imbalance of the inhibitory versus excitatory input directly relates to the symptoms seen in Huntington’s disease such as the inability to control voluntary movements termed chorea, the inability to control voluntary saccadic ocular movements, the cognitive inability to plan and determine the direction of movement, and the inability to control the emotional and motivational aspects of the movement. There is currently no cure for Huntington’s disease but there is a symptomatic treatment for the chorea and psychiatric conditions. Further research is being done to determine the pathophysiology behind the Hungtintin protein to allow for a targeted treatment regimen while also looking into reliable biomarkers for the progression of Huntington’s disease.

A rare case of isolated dextrocardia

Dextrocardia is a clinical condition in which heart is located on the right side of the chest cavity. Dextroversion is a result of early interruption of normal embryological development and therefore, rarely occurs without other cardiac and noncardiac anomalies. Isolated dextrocardia is a benign condition. It can often be associated with other congenital anomalies which can lead to failure to thrive, breathing difficulties, recurrent infections in new borns and neonates. It presents in situs solitus and situs inversus. Among them Dextrocardia with situs solitus is very rare. We are here presenting a case of dextrocardia with situs solitus.

Partial anomalous pulmonary venous connection: state-of-the-art review with assessment using a multidetector computed tomography angiography.

Pulmonary venous anomalies occur as a result of failure in normal embryological development. These anomalies may present as a spectrum ranging from normal variation to partial anomalous pulmonary venous connection (PAPVC) and total anomalous pulmonary venous connection (TAPVC). Though not rare, PAPVC is an uncommon anomaly in which some of the pulmonary veins abnormally connect and drain into the vascular compartments other than the left atrium (LA); however, the others drain normally into the LA. The clinical presentation and severity of affected patients depend on the morphological heterogeneity of the disease. PAPVC associated with other complex conge-nital cardiac diseases present early and are more severe than isolated PAPVC-associated atrial septal defect only. This radiological review gives a detailed description of PAPVC in terms of morphological variability and associated anomalies along with a discussion of the role of multidetector dual-source computed tomography scan in the diagnostic assessment.

Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors.

Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with concomitant expression of stem-cell markers may facilitate HML-2 expression. Future studies could utilize HML-2 as potential diagnostic criteria, use its expression as a treatment biomarker, and investigate the efficacy of therapies targeting cells with high HML-2 expression.

A Practical Approach to Diagnosis of Spinal Dysraphism.

Spinal dysraphisms (SDs) are congenital malformations of the spinal cord, determined by derangement in the complex cascade of embryologic events involved in spinal development. They represent a heterogeneous group ranging from mild clinical manifestations-going unnoticed or being discovered at clinical examination-to a causal factor of life quality impairment, especially when associated with musculoskeletal, gastrointestinal, genitourinary, or respiratory system malformations. Knowledge of the normal embryologic development of the spinal cord-which encompasses three main steps (gastrulation, primary neurulation, and secondary neurulation)-is crucial for understanding the pathogenesis, neuroradiologic scenarios, and clinical-radiologic classification of congenital malformations of the spinal cord. SDs can be divided with clinical examination or neuroradiologic study into two major groups: open SDs and closed SDs. Congenital malformations of the spinal cord include a wide range of abnormalities that vary considerably in imaging and clinical characteristics and complexity and therefore may represent a diagnostic challenge, even for the experienced radiologist. Online supplemental material is available for this article. ©RSNA, 2021.

Magnetic resonance imaging of the fetal musculoskeletal system.

Diagnosing musculoskeletal pathology requires understanding of the normal embryological development. Intrinsic errors of skeletal development are individually rare but are of paramount clinical importance because anomalies can greatly impact patients' lives. An accurate assessment of the fetal musculoskeletal system must be performed to provide optimal genetic counseling as well as to drive therapeutic management. This manuscript reviews the embryology of skeletal development and the appearance of the maturing musculoskeletal system on fetal MRI. In addition, it presents a comprehensive review of musculoskeletal fetal pathology along with postnatal imaging.

Congenital Heart Defects in the Context of Typical Development and Circulation

Solid foundational knowledge of the normal embryological development of the heart and great vessels is essential for understanding the etiology of various congenital heart defects (CHDs). As an increasingly diagnosed category of pathologies and overall the leading cause of neonatal morbidity, CHDs are often well tolerated when the developing human is in utero. Clinical sequelae, the signs and symptoms of patients with CHDs, become apparent after birth when the fetus no longer has access to a placenta and must use solely its own anatomy to provide and circulate the appropriate blood gases. CHDs can be divided into two major categories: critical, those which are life‐threatening and require surgery in infancy, and non‐critical, those which are not immediately life‐threatening and do not necessarily require surgery immediately or at all. One fundamental piece of information for the diagnosis of any CHD is whether or not the individual is cyanotic, and furthermore which specific tissues are subjected to this oxygen deficiency. Taussig’s classification of congenital heart defects includes those with no shunting of blood, those with a left to right shunt and acyanosis, and those with a right to left shunt and subsequent cyanosis. In the typical fetus, blood enters the right atrium of the heart at fairly high pressure. Some of this blood is entering via the inferior vena cava, which in the fetus contains some highly oxygenated blood via the ductus venosus and some blood of a low oxygenation rate that flowed through the developing liver tissues. Due to higher pressures on the right side of the fetal heart than the left, most blood passes through the foramen ovale and into the left atrium. This is a normal right to left shunt only in the fetus. When the fetus is born and air is introduced to the respiratory system the pressures change. Absent placental circulation leads to a decrease in pressure on the right side of the heart and increased pulmonary blood flow leads to an increase in pressure on the left side of the heart, specifically between the atria. This ex utero pressure differential closes the foramen ovale to form a fossa ovalis and no patent communication between the atria. The normal fetal right to left shunt should no longer be present. Since pulmonary vascular resistance is now lower than systemic vascular resistance, the blood flow in the ductus arteriosus between the pulmonary trunk and arch of the aorta reverses, the shunt constricts, and then forms into the ligamentum arteriosum. When these processes or those of cardiac septation occur incorrectly then the result may be a CHD. Proper identification of the pathological anatomy and etiology is relevant for understanding both normal and abnormal developmental processes in cardiac and great vessel morphology.

Androgen Insensitivity Syndrome: Drawbacks of the Medical Services

The normal embryological development, anatomical structural setup and physiological functionality of the genital system...

Anomalous origins of the coronary arteries: current knowledge and future perspectives.

The purpose of this review is to survey the contemporary literature surrounding congenital anomalies of origin of the coronary arteries and to identify remaining gaps in knowledge. In recent years, lineage tracing analyses and mechanistic studies in model organisms have enhanced our understanding of the normal embryologic development of the coronary arteries, and how disruption of this intricate process can lead to congenital coronary anomalies. The true incidence of these anomalies remains unknown. Although a majority of cases are believed to be clinically silent, clinical presentation varies widely, from asymptomatic to sudden cardiac death. Cardiac computed tomography angiography and/or magnetic resonance angiography are the mainstay diagnostic modalities. Management of anomalous coronary arteries depends on the morphology and clinical presentation. Surgery is the gold-standard treatment for anomalous left coronary artery arising from the pulmonary artery and anomalous aortic origin of a coronary artery with intramural or interarterial course. Several large multicenter initiatives are currently underway and should help address some of the numerous knowledge gaps surrounding the evaluation and management of anomalous coronary arteries.

Evaluating Learning Strategies for Independent Lifelong Learning Approaches

Students in integrated basic science courses in which normal and abnormal human embryological development is taught were given the option of using different learning tools to achieve competency of the assigned developmental topics. The goal of this investigation was to use a student survey to assess the value of each learning tool for the student, and whether any of these learning tools were of value to them in developing potential life‐long learning approaches. The available learning tools for the students included: assigned textbook reading, Word document handout of material with directed learning objectives/questions, video presentation of significant material, in‐class powerpoint lecture, self‐assessment multiple‐choice quiz questions, and self‐assessment multiple‐choice vignette questions. All learning tools were available to the students. A brief student survey was developed to assess the value of each recommended learning tool using a value scale of 0–5, with 5 being the highest value. In addition, students were asked to describe briefly why they found a specific learning tool beneficial to their learning of the subject material. A second question asked if any of these learning tools helped them develop potential life‐long learning approaches, and if so, which of these learning tools was most beneficial. When assessing the value of each learning tool to the student's learning, the students valued the quiz and vignette questions highest because it directed their learning to the clinical relevance of the topic covered in the Word document handout and the lecture information given via the video recording or powerpoint presentation. The textbook was valued lowest, but it was assessed to be valuable as a resource for more detailed information. When assessing the various learning tools for developing lifelong learning approaches, the use of clinical quiz and vignette questions was valued twice that of handouts or lecture type presentations. Written comments indicated that the questions were valued highly because the clinical scenarios emphasize the need to understand basic developmental processes. Use of a textbook for life‐longing learning was rated very low; however, searching the internet for answers was given as an alternative. The survey strongly suggests that clinical cases focusing on the learning objectives for a topic greatly raise the desire to learn, and that the use of multiple‐choice quiz and vignette questions significantly strengthens learning of the important topics.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Normalized second and fourth finger lengths in male and female partners and IVF cycle outcomes.

Hox genes are involved in limb formation during normal embryological development. Their modulation by circulating maternal oestrogens and androgens determines the length of the second and fourth fingers of the adult hand. Do these same intrauterine hormone levels also determine fertility outcomes in the adult? To study the association between the length of the second and fourth fingers of both partners undergoing IVF (as a surrogate of their previous intrauterine exposure to oestrogens and androgens) with treatment outcome after IVF, data corresponding to 256 IVF cycles were analysed. Finger length was normalized to the individual height. In the female partner, a longer normalized second finger length of the left (2DLN) hand, reflecting a high intrauterine exposure to oestrogens, was independently and significantly (P = 0.011) associated with obtaining at least one top-quality embryo in a multivariate model. Conversely, in the male partner a longer normalized fourth finger length of the left hand (4DLN), reflecting a high intrauterine exposure to androgens, was independently and significantly (P = 0.032) associated with obtaining at least one top-quality embryo in the same multivariate model. In the female partner, 2DLN was inversely and significantly (P = 0.01) associated with achievement of pregnancy. Intrauterine exposure to high levels of oestrogens and androgens in females and males, respectively, predisposes to the production of higher-quality embryos under in-vitro conditions during adulthood. Paradoxically, this also seems to result in a lower pregnancy rate.

Branchial cleft cysts: a pictorial review.

Cystic masses of the neck may represent a wide variety of pathological conditions. Among these, branchial anomalies are the commonest paediatric congenital lesions of the head and neck. This article intends to review this condition under the same headings, as well as facilitate their diagnosis with the help of appropriate radiological findings of patients diagnosed with these anomalies. In order to make an accurate diagnosis, it is imperative to have an idea about the possible differentials, and the normal embryological development of the branchial arches, as well as their anomalies, in the form of sinuses, fistulae, and cysts, with their features and subtypes. The medical history of the patient and clinical manifestations helps in suspecting branchial cleft cysts; confirmatory imaging modalities include computed tomography, magnetic resonance imaging, ultrasonography, and fine-needle aspiration. The mainstay of management is usually by surgical excision. The location, clinical picture, and radiological correlation, along with a strong degree of suspicion for the condition, facilitates the diagnosis of this relatively common embryological anomaly.

A Case of Bilateral Craniofacial Cleft From Amniotic Band Syndrome

Amniotic band syndrome [ABS] or amniotic disruption complex is defined as a destructive process of fetal damage in a random non symmetrical distribution, which is not attributable to aberrations in normal embryologic development processes .The mechanism has been considered to be initiated in rupture of the amnion, with the fetus then coming into contact with the chorionic surface of the amniotic membrane ,to which it adheres or becomes entwined by fibrous strands .As the fetus grows ,The tethered regions are progressively distorted, leading to constrictions, amputations ,Slash defects, and body wall or cranial defects .The severity varies from a single constrictive ring of a digit to lethal thoraco abdominal eviscerations or craniofacial distruction.ABS is a rare disorder in which bands of mesoderm that emanate from the chorionic side of the amnion and insert on the fetal body can lead to a wide variety of disfiguring and disabling malformations[1,2] . ABS results in the amputation of the fingers or limbs, associated with a wide spectrum of congenital anomalies usually involving the trunk and craniofacial regions including the skull. AbBS is in general sporadic and the incidence is approximately 1 in 15,000 live birth. Characterized by a destructive fetal process that is initiated by rupture of the amnion. Proposed as a sequel of intrauterine rupture of the amnion resulting in oligohydramnios and passage of fetus to chorionic cavity .The fetus subsequently becomes adherent to intertwined in, and tethered by fibrous mesodermic bands .As the fetus grows, its anatomy is distorted .This may lead to cranial or body wall defects or and although been reports of associated malformations of internal structures. [3, 4] ABS that involves craniofacial region may present as cleft lip or palate , oblique or transverse facial cleft .These craniofacial anomalies in ABS are typically often bizarre and frequently non-embryological .The exact cause of ABS is still unknown .This lack of direct evidence has led to the proposal of two main etiological theories. The extrinsic and the intrinsic 4. The extrinsic theory states that the band of ruptured amnion causes an extrinsic compression which then results in constriction rings and other deformities of the developing fetus, while the intrinsic theory holds that germ cell deficiencies result in the malformation of the affected parts [4]. Treatment is usually carried out after birth when plastic and reconstructive surgery is considered to treat the resulting deformities. [4, 5] (Ethiopian Journal of Reproductive Health 2016; 8:50-55)

Rete mirabile associated with pial arteriovenous fistula: imaging features with literature review

A rete mirabile is a vascular network of intercommunicating small arteries or arterioles that replace the definitive adult artery supplying the brain. It supplies the brain in lower mammals but...

The Developing Skull Base: Anatomical and Surgical Issues for Hearing Implants

In this roundtable discussion, the developmental aspects of the inner ear, as well as the anatomical conditions of young children's skulls, are presented in order to make the different malformations of the inner ear understandable and to give hints for insertion procedures of the cochlear implants. The normal embryologic development of the inner ear, as well as of the middle ear, is explained and the typical disturbances are discussed. In the next part, two different classification schemes (Jackler, Sennaroglu) of the labyrinthine malformations are given and related to the developmental processes. The following entities are discussed: complete labyrinthine aplasia (Michel dysplasia), common cavity, cochlear aplasia, labyrinthine hypoplasia, cochlear and vestibular hypoplasia, and incomplete partition. Especially it will be outlined that malformations of the facial nerve must be expected if malformations of the inner ear are present. The special anatomical conditions of young children's skull are outlined and demonstrated. The following conclusions from the presentation can be summarized: Embryology is important to understand the malformations, skin incisions should not harm the facial nerve, which is superficially positioned directly under the skin in young children, an injury of the dura, sigmoid sinus or surface of the brain or the cerebellum is easily possible due to the very thin osseous structures, and furthermore the growth potential of the osseous skull can be responsible for lost or dislocation of the electrodes of cochlear implants. For this growth potential, especially the sutures and the mastoid fontanelle are responsible.

Congenital prepubic sinus: A case report and review of the literature

Abstract Congenital prepubic sinus (CPS) is an extremely rare anomaly, which is often associated with purulent discharge from a midline opening overlying the pubis. CPS was first described by Campbell et al. in 1987 and they suggested that it might represent a variation in normal embryological development. Several theories have been proposed regarding the pathogenesis of CPS. However, the etiology of CPS is still unclear because the anatomical and pathological features of CPS often differ from each other. We report a case of CPS and review the literature to improve the global understanding of CPS.