Branchial Arches Research Articles

Congenital Sternoclavicular Sinus-Case Series of a Rare Lower Neck Deformity.

We encountered patients with a congenital cutaneous sinus tract in the sternoclavicular joint region, which we designate as "congenital sternoclavicular sinus (CSCS)." The aim of this investigation is to enhance recognition of this subtle yet noteworthy entity and develop standardized protocols for its management. Between 2013 and 2023, 172 patients, including 78 males and 94 females, were referred to our institution for the management of CSCS. Clinical charts were retrospectively reviewed. The majority of patients (60.5%) were young children below 3 years of age, with only six adult patients and a median age of 27.5 months. The left side was implicated in 157 cases (91.3%). In 146 cases (84.9%), a faint skin streak was noted above the orifice. Yet, no pharyngeal sinus tracts were detected, either through barium swallow studies or direct laryngoscopy. All skin lesions featured a diminutive orifice near the sternoclavicular joint, with the tract extending deeply into the subcutaneous tissue and terminating blindly, short of entering the joint, after a distance of 10 mm (ranging from 5 to 21 mm). Histopathological analysis revealed that the epithelial lining predominantly consisted of stratified squamous epithelium (87.8%), with ciliated columnar epithelium accounting for the remaining 12.2%. CSCS, though infrequent, presents with distinctive pathological and clinical features. The condition predominantly affects the left sternoclavicular joint region, with the notable "skin streak sign" aiding in diagnosis. We considered CSCS as one disease entity of branchial arch anomalies. Complete surgical excision offers a definitive cure. 4 Laryngoscope, 134:4402-4408, 2024.

Paired fins in vertebrate evolution and ontogeny.

The origin of paired appendages became one of the most important adaptations of vertebrates, allowing them to lead active lifestyles and explore a wide range of ecological niches. The basic form of paired appendages in evolution is the fins of fishes. The problem of paired appendages has attracted the attention of researchers for more than 150 years. During this time, a number of theories have been proposed, mainly based on morphological data, two of which, the Balfour-Thacher-Mivart lateral fold theory and Gegenbaur's gill arch theory, have not lost their relevance. So far, however, none of the proposed ideas has been supported by decisive evidence. The study of the evolutionary history of the appearance and development of paired appendages lies at the intersection of several disciplines and involves the synthesis of paleontological, morphological, embryological, and genetic data. In this review, we attempt to summarize and discuss the results accumulated in these fields and to analyze the theories put forward regarding the prerequisites and mechanisms that gave rise to paired fins and limbs in vertebrates.

Developmental, Physiological and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of sarcomeric myosin heavy chains (MyHCs) that they express and changes in MyHC expression during phylogeny. Myogenic progenitors from the mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles (EOMs) express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB (nmMyH IIB). They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC and cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift toward expressing slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs that they express. Thyroid hormone shifts MyHC 2A toward 2B in jaw muscles, laryngeal muscles and possibly extraocular muscles. This review highlights the fact that the pattern of myosin expression in mammalian craniofacial muscles is principally influenced by the complex interplay of cell lineages, neural impulse patterns, thyroid and other hormones, functional demands and body mass. In these respects, craniofacial muscles are similar to limb muscles, but they differ radically in the types of cell lineage and the nature of their functional demands.

Dyrk1a is required for craniofacial development in Xenopus laevis.

Loss of function variations in the dual specificity tyrosine-phosphorylation-regulated kinase 1 A (DYRK1A) gene are associated with craniofacial malformations in humans. Here we characterized the effects of deficient DYRK1A in craniofacial development using a developmental model, Xenopus laevis. Dyrk1a mRNA and protein were expressed throughout the developing head and both were enriched in the branchial arches which contribute to the face and jaw. Consistently, reduced Dyrk1a function, using dyrk1a morpholinos and pharmacological inhibitors, resulted in orofacial malformations including hypotelorism, altered mouth shape, slanted eyes, and narrower face accompanied by smaller jaw cartilage and muscle. Inhibition of Dyrk1a function resulted in misexpression of key craniofacial regulators including transcription factors and members of the retinoic acid signaling pathway. Two such regulators, sox9 and pax3 are required for neural crest development and their decreased expression corresponds with smaller neural crest domains within the branchial arches. Finally, we determined that the smaller size of the faces, jaw elements and neural crest domains in embryos deficient in Dyrk1a could be explained by increased cell death and decreased proliferation. This study is the first to provide insight into why craniofacial birth defects might arise in humans with variants of DYRK1A.

A new species of trout from the Köprüçay River, a drainage of Mediterranean Sea, Türkiye (Salmoniformes, Salmonidae)

Salmo ekmekciae, new species, is described from the Köprüçay River, a drainage of Mediterranean Sea. It is distinguished from Salmo species in adjacent water by having 9–10 parr marks on flank; 11–13 scale rows between end of base of adipose-fin and lateral line; 22–24 gill rakers on first gill arch; a shorter distance between adipose-fin and caudal-fin base; a slenderer caudal peduncle; and a slenderer body at adipose-fin origin. According to the Bayesian, and maximum likelihood analyses, Salmo ekmekciae cyt b gene resulted in coherent trees supported by high bootstrap values.

A Rare Case of Bilateral Second Arch Branchial Fistulae; A Case Report.

Branchial arch anomalies are considered congenital defects that can occur during fetal development. They may present as cysts, sinuses, or fistulae. Anomalies of the second branchial arch are the most common. The existence of bilateral complete fistulae is exceptionally rare. In this case report, a 5-year-old boy presented with recurrent episodes of bilateral neck swelling and watery discharge from openings on the anterolateral sides of his neck since birth. He was diagnosed with bilateral branchial fistulae after confirmation via a contrast-enhanced CT scan. Surgery was performed to entirely excise the fistula tracts bilaterally. Additionally, a bilateral tonsillectomy was performed to help prevent recurrence.

Neglected Preauricular Sinus Abscess Extending to the Scalp: A Case Report of Complications and Management Challenges

Preauricular sinus, a congenital malformation resulting from incomplete fusion of the first and second branchial arches, is a relatively common condition with a reported prevalence of 0.1% to 0.9%. While mostly asymptomatic, it can lead to abscess formation when infected. We present a unique case of a neglected preauricular sinus abscess that extended to the scalp, causing significant complications. The report discusses the clinical presentation, diagnostic approach, treatment modalities, and potential complications associated with this unusual and severe presentation. Prompt and appropriate management, combined with conservative treatment and surgical intervention, led to successful outcomes. This case highlights the importance of recognizing potential risks and implementing a systematic approach in managing recurrent preauricular sinus abscesses.

Effect of valproic acid on the formation and migration of cranial neural crest cells at the early developmental stages in rat embryos.

Cranial neural crest cells (NCCs) are critical for craniofacial development. The administration of valproic acid (VPA) to pregnant females causes craniofacial malformations in offspring. However, the in vivo influence of VPA on mammalian cranial NCCs remains unclear. In this study, we aimed to elucidate the developmental stage-specific effect of VPA on cranial NCCs through the administration of a single dose of VPA to pregnant rat females immediately prior to the formation of the cranial neural crest (NC). We performed whole-mount immunohistochemistry or in situ hybridization to examine localization changes of gene transcripts associated with the epithelial-mesenchymal transition of the cranial NC (i.e., cranial NCC formation) and cranial NCC migration. The results showed that Hoxa2 mRNA was abnormally detected and Sox9 mRNA expression was decreased in the midbrain-rhombomere (R) 1/2 NC, which forms cranial NCCs that migrate to the frontonasal mass (FNM) and branchial arch (BA) 1, through VPA administration, thus reducing the formation of SNAI2-positive NCCs. Hoxa2-positive NCCs were detected normally in BA2 and abnormally in FNM and BA1, which are normally Hox-free, implying VPA-induced abnormal cranial NCC migration. In vitro verification experiments using the whole embryo culture system revealed that midbrain-R4 NCC migration was abnormal. These results indicate that VPA reduces the formation/delamination of the midbrain-R1/2 NCCs in a developmental stage-specific manner and subsequently causes the abnormal migration of R4 NCCs, which suggests that the abnormal formation and migration of cranial NCCs contribute to the inhibition of axonal elongation in the trigeminal nerve and a reduction in head size.

Identification of new amoebae strains in rainbow trout (Oncorhynchus mykiss, Walbaum) farms affected by nodular gill disease (NGD) in Northeastern Italy.

Nodular gill disease (NGD) is an emerging condition associated with amoeba trophozoites in freshwater salmonid farms. However, unambiguous identification of the pathogens still must be achieved. This study aimed to identify the amoeba species involved in periodic NGD outbreaks in two rainbow trout (Oncorhynchus mykiss) farms in Northeastern Italy. During four episodes (February-April 2023), 88 fish were euthanized, and their gills were evaluated by macroscopic, microscopic and histopathological examination. The macroscopic and microscopic severity of the lesions and the degree of amoebae infestation were scored and statistically evaluated. One gill arch from each animal was put on non-nutrient agar (NNA) Petri dishes for amoeba isolation, cultivation and subsequent identification with SSU rDNA sequencing. Histopathology confirmed moderate to severe lesions consistent with NGD and mild to moderate amoeba infestation. The presence of amoebae was significantly correlated with lesion severity. Light microscopy of cultured amoebae strains and SSU rDNA analysis revealed the presence of a previously characterized amoeba Naegleria sp. strain GERK and several new strains: two strains from Hartmannelidae, three vannelid amoebae from the genus Ripella and cercozoan amoeba Rosculus. Despite the uncertainty in NGD etiopathogenesis and amoebae pathogenic role, identifying known and new amoebae leans towards a possible multi-aetiological origin.

Branchial Arch Remnants in the Pediatric Patient Under Local Anesthesia

Objective: Branchial arch remnants are a well-encountered pathology in pediatric patients. In the majority of cases, these vestiges are superficial and benign, save for minor cosmetic deformity or discomfort. Although branchial arch remnants in the form of skin vestiges are commonly removed, there remains a lack of in-depth study regarding appropriate protocol and experience under local anesthesia. Design: A retrospective review of subjects undergoing first branchial arch vestige excision utilizing local anesthesia was conducted (2017-2021). Demographics were recorded, including age, sex, comorbidities, vestige location, presence of tracts, post-operative complications, and significant associations. Results: A total of 178 subjects were identified for inclusion. The mean patient age during the procedure was 18.4 ± 38.3 months. A total of 34 patients presented with a current or prior comorbidity (24.7%). The most common location of the branchial remnant was the preauricular region (79.2%). Most patients were without complication (96.1%). Secondarily developed branchial anomalies were significantly associated with complications as compared to congenital anomalies (22.2% vs 3.0%, P < .042). Additionally, patients with a past medical history were significantly more likely to develop a post-operative complication (71.4% vs 22.6%, P < .13). Conclusion: In-office branchial remnant removal is a safe procedure in the young pediatric patient. Complication rates are low; patients with a significant past medical history may be more likely to incur postoperative complications. Additionally, patients with secondary vestige development may also be more likely to develop complications. Further in-office procedures are encouraged.

Mechanistic study of transcription factor Sox18 during heart development

Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.

A Case of Auricle Deformity With 2nd Branchial Cleft Anomaly in Patient With Branchio-Otic Syndrome

Branchio-oto-renal (BOR) Syndrome is a rare autosomal dominant genetic disorder characterized by features such as branchial arch anomalies, hearing loss, preauricular fistula, auricular malformations, and renal abnormalities. Also, BOR syndrome without renal anomalies is referred to as branchio-otic syndrome. In this report, we present a case of a 50-year-old female patient with bilateral type 2 branchial arch anomalies, both preauricular fistula, bilateral inner ear malformations, bilateral sensorineural hearing loss, and right auricular malformation. The patient underwent surgical treatment. This report is the first documentation in Korea of auricular malformation in BOR syndrome, where the patient’s family exhibited a typical autosomal dominant inheritance pattern.

Management of Lateral Canthal Coloboma in Goldenhar Syndrome: A Rare Case Report

Introduction : Goldenhar syndrome is a rare congenital disorder characterized by a wide range of physical anomalies affecting the face, ears, eyes, and spine.
 Case Illustration : Patient, female 19-year-old, complained of growing mass and blurry vision on right eye since childhood. The patient also has an asymetric face with the right side being smaller then left. She also has hearing disorder on her right ear. Ophthalmology examination revealed right eye's visual acuity is 6/120, lateral canthus coloboma , trichiasis and mass on the inferior palpebral, and conjunctiva attached to the cornea. Left eye is within normal limit. The right ear appears deformed, with no ear canal and preauricular skin tags. Patient underwent conjungtiva tumor excision and given labia mucosa graft with canthoplasty. Histology examination revealed benign lipomatous tumor. Patient feels more confident after oculoplasty surgery.
 Discussion : Goldenhar syndrome is a rare condition caused by abnormal development of the first and second branchial arches. It is characterized by a wide range of ocular features, including eyelid and iris coloboma, conjungtiva dermoid or dermolipoma, and more. Beside ocular features, other features are ear malformations, facial asymmetry, cleft lip or palate, and vertebral anomalies. It was unique case because an unformed canthus was found due to a large of conjunctival fornix mass. Appropriate management is necessary for a fulfilling life, though the disorder can have significant psychosocial effects.
 Conclusion : Goldenhar syndrome is a rare disease with numerous symptoms and its management is crucial for individuals to have a fulfilling life despite its potentially significant psychosocial impacts.

Loss of Neogenin alters branchial arch development and leads to craniofacial skeletal defects.

The formation of complex structures, such as the craniofacial skeleton, requires precise and intricate two-way signalling between populations of cells of different embryonic origins. For example, the lower jaw, or mandible, arises from cranial neural crest cells (CNCCs) in the mandibular portion of the first branchial arch (mdBA1) of the embryo, and its development is regulated by signals from the ectoderm and cranial mesoderm (CM) within this structure. The molecular mechanisms underlying CM cell influence on CNCC development in the mdBA1 remain poorly defined. Herein we identified the receptor Neogenin as a key regulator of craniofacial development. We found that ablation of Neogenin expression via gene-targeting resulted in several craniofacial skeletal defects, including reduced size of the CNCC-derived mandible. Loss of Neogenin did not affect the formation of the mdBA1 CM core but resulted in altered Bmp4 and Fgf8 expression, increased apoptosis, and reduced osteoblast differentiation in the mdBA1 mesenchyme. Reduced BMP signalling in the mdBA1 of Neogenin mutant embryos was associated with alterations in the gene regulatory network, including decreased expression of transcription factors of the Hand, Msx, and Alx families, which play key roles in the patterning and outgrowth of the mdBA1. Tissue-specific Neogenin loss-of-function studies revealed that Neogenin expression in mesodermal cells contributes to mandible formation. Thus, our results identify Neogenin as a novel regulator of craniofacial skeletal formation and demonstrates it impinges on CNCC development via a non-cell autonomous mechanism.

ONTOGENETIC TRANSFORMATIONS OF THE FACIAL RUDIMENTS OF THE SKULL BONES IN THE FIRST TRIMESTER OF PRENATAL HUMAN ONTOGENESIS

The purpose of the research – to clarify the sources and terms of the rudiments, to findout the age-specific dynamics of changes and features of the morphogenesis of the bonesof the facial part of the skull in the first trimester of intrauterine development (IUD).Material and methods. Serial microspecimens of 20 embryos (4.0-13.5 mm parietalcoccygeal length (PCL)) and 25 prefetuses (14.0-80 mm PCL) covering the period fromthe 4th to the 12th weeks of the IUD were studied. A complex of methods of morphologicalresearch is applied: creation of series of consecutive histological sections, microscopy,morphometry, three- dimensional reconstruction.The results. The rudiments of the bones of the facial part of the skull are the mesenchyme ofthe five facial outgrowths of 4-week-old human embryos. The rudiment of the anterior partof the ectomeningeal capsule has a neuroectodermal origin, and its outer layer forms thesplanchnocranium – the rudiments of the frontal, zygomatic, nasal, lacrimal bones, vomer,and jaws. In 5-week-old embryos, the process of fusion of the frontal process, the medialand lateral nasal processes of maxillar process and mandibular process of the I branchialarch and the hyoid branchial arch begins, resulting in the formation of nasal pits and the primary nasal cavity. In 6-week-old embryos, the rudiments of the mandible are formed.During the 7-8th week of IUD, the cartilaginous rudiment of the skull becomes a continuousstructure. The mesenchyme of the mandibular branchial arch is the source of the developmentof the frontal, lacrimal, nasal bones, vomer, and premaxillary part of the maxilla. The sourcesof development of the maxilla and zygomatic bone are the mesenchyme of the maxillaryprocess of the I branchial arch, while the mandible and the tympanic part of the temporal boneare formed from the mesenchyme of the mandibular process of this branchial arch.Conclusions. Violation of the proliferation of processes of the I branchial arch, theirconsolidation and transformation of the branchial apparatus at the end of the embryonic period(5-6th week of IUD) can lead to the appearance of severe congenital defects of the face. Also,the 7th and 10th weeks of IUD are critical periods of the morphogenesis of the rudiments of thehuman skull, the time of the possible appearance of variants of the structure or birth defects.

Management of a recurrent third branchial arch fistula using combined endoscopic and open approach

Branchial cleft anomalies are rare, congenital lesions, that occur due to the maldevelopment of the branchial apparatus, during fetal maturation. Anomalies of the third and fourth arch contribute to a very small proportion of these. Most cases are detected in childhood, either as a cyst, sinus or fistula in the neck. Some of the common treatment approaches to third branchial cleft fistulas include endoscopic cauterization, open cervical fistulectomy and, in cases of recurrence, selective neck dissection. Here, we present a case of recurrent branchial fistula of the third arch, wherein we used a combined cervical and intraoral approach, conserving the thyroid cartilage, to achieve a complete excision of the fistula tract.

Live imaging of Fibronectin 1a-mNeonGreen and Fibronectin 1b-mCherry knock-in alleles during early zebrafish development

Within the developing embryo, cells assemble and remodel their surrounding extracellular matrix during morphogenesis. Fibronectin is an extracellular matrix glycoprotein and is a ligand for several members of the Integrin adhesion receptor family. Here, we compare the expression pattern and loss of function phenotypes of the two zebrafish fibronectin paralogs fn1a and fn1b. We engineered two fluorescently tagged knock-in alleles to facilitate live in vivo imaging of the Fibronectin matrix. Genetic complementation experiments indicate that the knock-in alleles are fully functional. Fn1a-mNeonGreen and Fn1b-mCherry are co-localized in ECM fibers on the surface of the paraxial mesoderm and myotendinous junction. In 5-days old zebrafish larvae, Fn1a-mNeonGreen predominantly localizes to the branchial arches, heart ventricle, olfactory placode and within the otic capsule while Fn1b-mCherry is deposited at the pericardium, proximal convoluted tubule, posterior hindgut and at the ventral mesoderm/cardinal vein. We examined Fn1a-mNeonGreen and Fn1b-mCherry in maternal zygotic integrin α5 mutants and integrin β1a; β1b double mutants and find distinct requirements for these Integrins in assembling the two Fibronectins into ECM fibers in different tissues. Rescue experiments via mRNA injection indicate that the two fibronectins are not fully inter-changeable. Lastly, we examined cross-regulation between the two Fibronectins and find fn1a is necessary for normal Fn1b fibrillogenesis in the presomitic mesoderm, but fn1b is dispensable for the normal pattern of Fn1a deposition.

Large Epidermoid Cyst in Submental Region: A Rare Case Report

Epidermoid cyst, specially in large size is one of the rare lesions of maxillofacial region, affects submental and sublingual region. The cyst develops from the entrapment of pluripotent ectodermal and mesodermal primordia, in the embryonic lines of fusion, when first and second branchial arches of each fuse in the midline, between third and fourth weeks of intrauterine life. After entrapment, this tissue shows gradual proliferation and ultimately transform to a cyst. A 19-year-old-boy presented with such a midline painless large swelling in the submental and sublingual region with diagnosis of epi dermoid cyst. After enucleation, the patient didn’t show any recurrence after 2 years follow up. J Bangladesh Coll Phys Surg 2024; 42: 92-96

Airway Challenges in a Child with Treacher Collins Syndrome having Ventricular Septal Defect, Oculofacial Malformations and Oesophageal Atresia: A Case Report

Treacher Collins Syndrome (TCS), also known as Franceschetti syndrome, is an autosomal dominant condition marked by various developmental anomalies confined to the head and face. It primarily affects craniofacial structures derived from the first and second branchial arches. Patients usually present with down-slanting palpebral fissures, mandibular hypoplasia, lower eyelid colobomas, external ear malformations, and hearing loss. Congenital heart defects and cryptorchidism are two other unusual anomalies. It is typically a bilateral condition. The symptoms and physical features of TCS can vary greatly from person to person. Some individuals may be affected so mildly that their condition goes undiagnosed, whereas others may develop serious, lifethreatening complications. Individuals with TCS may require specialised airway management due to a narrow mouth aperture and micrognathia. They are best served by an interprofessional team that can coordinate all aspects of their care. Timely detection and management can improve the quality of life for these patients. The present case report presents the airway challenges in an eightyear-old child with TCS who has congenital malformations and presented with swallowing difficulty, which was later diagnosed as oesophageal atresia.

Blockbuster Laryngeal Mask Airway as a Rescue Device in Paediatric Patient with Retrognathia Posted for Microtia Reconstruction Surgery: A Case Report

The first and second branchial arches, along with the first branchial cleft, contribute to the development of ear and mandible. Children with microtia can have retrognathia or micrognathia and have challenging airway management. Managing the airway in these patients presents a significant challenge for anaesthesiologists as they have the potential for upper airway obstruction and challenging tracheal intubation because of facial deformities. Although awake fiberoptic intubation is a well-accepted method for handling difficult intubations, it can be uncomfortable and stressful for paediatric patients. Moreover, it demands expertise and is unsuitable for patients unwilling to undergo awake intubation. This case report highlights the use of the blockbuster Laryngeal Mask Airway (LMA) in an 11-year-old retrognathic child with microtia with anterior larynx scheduled for auricular reconstruction surgery. There was a failure to secure the airway with multiple attempts at traditional intubation and the supraglottic airway device i-gel, as the child had an anterior larynx and Cormack Lehane (CL) grading of 4 on direct laryngoscopy. The blockbuster LMA, distinguished by its innovative design facilitating both ventilation and intubation through an integrated channel, emerged as a pivotal alternative. The supraglottic device is not the technique of choice, but it can definitely be an alternative and could be life-saving in situations where fiberoptic bronchoscopy and tracheostomy are not available.