Liquid Biopsy in Head and Neck Cancer: Its Present State and Future Role in Africa.

The rising mortality and morbidity rate of head and neck cancer (HNC) in Africa has been attributed to factors such as the poor state of health infrastructures, genetics, and late presentation resulting in the delayed diagnosis of these tumors. If well harnessed, emerging molecular and omics diagnostic technologies such as liquid biopsy can potentially play a major role in optimizing the management of HNC in Africa. However, to successfully apply liquid biopsy technology in the management of HNC in Africa, factors such as genetic, socioeconomic, environmental, and cultural acceptability of the technology must be given due consideration. This review outlines the role of circulating molecules such as tumor cells, tumor DNA, tumor RNA, proteins, and exosomes, in liquid biopsy technology for the management of HNC with a focus on studies conducted in Africa. The present state and the potential opportunities for the future use of liquid biopsy technology in the effective management of HNC in resource-limited settings such as Africa is further discussed.

The genetic determinants of oral diseases in Africa: The gaps should be filled.

Oral diseases are a major health concern and are among the most prevalent diseases globally. This problem is becoming more prominent in the rapidly growing populations of Africa. It is well documented that Africa exhibits the most diverse genetic make-up in the world. However, little work has been conducted to understand the genetic basis of oral diseases in Africans. Oral health is often neglected and receives low prioritisation from funders and governments. The genetic determinants of highly prevalent oral diseases such as dental caries and periodontal disease, and regionally prevalent conditions such as oral cancer and NOMA, are largely under-researched areas despite numerous articles alluding to a high burden of these diseases in African populations. Therefore, this review aims to shed light on the significant gaps in research on the genetic and genomic aspects of oral diseases in African populations and highlights the urgent need for evidence-based dentistry, in tandem with the development of the dentist/scientist workforce.

The challenge of unidentified decedents in Africa: The need for training and research in forensic odontology to strengthen a multidisciplinary approach.

Introduction: The management of unidentified decedents suspected to be undocumented migrants is a growing humanitarian crisis in Africa. Identification of the dead and the right of the family to know the fate of a decedent is a fundamental human right. Forensic odontology methods can provide helpful and assisting information in the identification even in challenging low-resource settings. South Africa and other countries that are part of significant migration routes face the problem of unidentified decedents. Discussion: The fundamental application of forensic odontology relies on the availability of good antemortem dental records. The state of dental records was reported to be suboptimal in South Africa and other African countries. Incorporating forensic odontology into the undergraduate training in the 23 dental schools in Africa will increase the understanding of the value of maintaining accurate dental records and potentially facilitate collaboration with dentists and forensic odontologists in cases where dental features can be used for identification. South Africa offers postgraduate training in forensic odontology, and prospects for research in Africa need to be explored. Conclusion: The development of a forensic odontology career path and research prospects will provide African countries with the potential for building multidisciplinary teams to assist in solving the challenge of unidentified decedents.

Craniofacial, dental, and molecular features of Pyle disease in a South African child.

INTRODUCTION: Pyle Disease (PD), or familial metaphyseal dysplasia [OMIM 265900], is a rare autosomal recessive condition leading to widened metaphyses of long bones and cortical bone thinning and genu valgum. We detail the oro-dental and molecular findings in a South African patient with PD. METHODS: The patient underwent clinical, radiographic and molecular examinations. An exfoliated tooth was analysed using scanning electron microscopy and was compared to a control tooth. RESULTS: The patient presented with marked Erlenmeyer-flask deformity (EFD) of the long bones and several Wormian bones. His dental development was delayed by approximately three years. The permanent molars were mesotaurodontic. The bones, including the jaws and cervical vertebrae, showed osteoporotic changes. The lamina dura was absent, and the neck of the condyle lacked normal constrictions. Ionic component analysis of the primary incisors found an absence of magnesium. Sanger sequencing revealed a novel putative pathogenic variant in intron 5 of SFRP4 (c.855+4delAGTA) in a homozygous state. CONCLUSION: This study has reported for the first time the implication of a mutation in the SFRP4 gene in an African patient presenting with PD and highlights the need for dental practitioners to be made aware of the features and management implications of PD.

Employing the London Atlas in the Age Estimation of a Select South African Population.

Dental age estimation in the living and deceased is a fundamental aspect of forensic sciences, civil cases, medico-legal proceedings and clinical dentistry. Accordingly, this study aimed to validate the accuracy and reproducibility of the London Atlas in a select South African sample of KwaZulu-Natal. In this cross-sectional study, 760 digital panoramic radiographs (n = 760) aged between 5.00 and 23.99 years were retrospectively reviewed through consecutive sampling. Each radiograph was assessed and assigned a dental age in accordance with the London Atlas of Human Tooth Development and Eruption by AlQahtani et al. (2010). The London Atlas overestimated age with a mean difference of -0.85 to -1.26 years in the selected South African sample of KwaZulu-Natal. A statistically significant difference between the chronological and estimated dental ages was recorded. Furthermore, the South African Black and Indian males had a higher overestimation of age than their female counterparts, with a mean difference of 0.13 and 0.07 years, respectively. This overestimation was less in the South African Indian population in comparison to the SA Black population. This outcome resulted in the creation of the KZN population- and sex-specific charts and atlases for the two selected cohorts of KwaZulu-Natal. The KZN Atlases were found to be more accurate in the selected sample, with a mean absolute error of 0.57 years and no statistically significant differences between the chronological and estimated dental ages.

The Application of the Cameriere's Methodologies for Dental Age Estimation in a Select KwaZulu-Natal Population of South Africa.

Background: The estimation of an individual's age is a fundamental component of forensic odontology. Literary reports found that the efficiency of Cameriere methodology for age estimation varied among many population groups. Therefore, this study aimed to determine the applicability of the Cameriere methods to a select South African population of the KwaZulu-Natal (KZN) province. Materials and Methods: This cross-sectional retrospective study was conducted on 840 digital panoramic radiographs that met the inclusion criteria. Dental maturity was determined through the morphometric analysis of the seven left permanent mandibular and maxillary teeth in accordance with Cameriere et al. (2006). Moreover, the dental age was also calculated using the South African Black Bayesian formulae of the Cameriere method by Angelakopoulos et al. (2019). The paired sample t-test or Wilcoxon's signed rank test assessed the significant difference between the chronological age and estimated dental age for the various formulae. A p-value < 0.05 was considered to be statistically significant. Results: The Cameriere et al. (2006) Italian formula and the South African Black Bayesian formulae of the Cameriere method by Angelakopoulos et al. (2019) underestimated and overestimated age in the South African Black and Indian population groups of the KZN province, respectively. Therefore, the authors generated a novel population-specific regression formulae (including and excluding third molars) using "step-wise regression analysis" and a "best-fit model" for the South African Black and Indian population groups of KZN. Conclusion: This study recommends that the population-specific formulae generated in this study be utilized in the KZN population to improve the accuracy of dental age estimation within this region.

Facial imaging to screen for fetal alcohol spectrum disorder: A scoping review.

Facial imaging tools have rapidly advanced in recent years and show potential for use in fetal alcohol spectrum disorder (FASD) screening and diagnosis. This scoping review describes the current state of evidence regarding the use of facial imaging being as a screening tool for FASD at a community level. This review follows the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for scoping reviews and is registered with the Open Science Framework (osf.io/e4xw6). An electronic search of five databases was conducted. The time frame was limited to the period 2006 to 2022. The search included any form of imaging of the head, neck, oral cavity, and dentition. Animal and antenatal studies were excluded, as were those using only brain imaging. The search retrieved 730 unique titles. After title, abstract, and full-text screening, 28 primary studies were included in this review. Most studies were conducted with South African participants. Imaging included 2D photographs, 3D stereophotogrammetry, 3D laser scanning, and radiographs. Various measurements and landmarks were used to discriminate FASD from non-FASD participants, which included anthropometry, face shape analysis, and facial curvatures. Methods of data processing, analysis, and modeling ranged from manual methods to fully automated systems utilizing artificial intelligence. The use of facial imaging to screen for and diagnose patients with FASD is a rapidly advancing field. Most studies in the field remain exploratory, attempting to find accurate, reliable, and consistent landmarks and measures across different populations. For community screening, none of the tools in this review in their current form completely fulfill all the identified properties of an ideal screening tool. More research and development are needed prior to advocating for the use of any tool listed and the ethical implications are yet to be fully explored.

Enamel Renal Syndrome: Protocol for a Scoping Review.

BACKGROUND: Enamel renal syndrome (ERS) (OMIM 204690) is a rare autosomal recessive disorder characterized by hypoplastic amelogenesis imperfecta, failed tooth eruption, intrapulpal calcifications, gingival enlargement, and nephrocalcinosis. The rarity of the condition and the variability of the phenotype has led to ERS not being fully characterized. OBJECTIVE: This scoping review aims to account for the range and current state of knowledge on ERS and synthesize these findings into a comprehensive summary, focusing on the pathophysiology, genotype-phenotype correlations, and patient management from a dental perspective. METHODS: The authors will conduct a systematic search of PubMed (MEDLINE), BioMed Central, EbscoHost Web, Web of Science, and WorldCat. We will include all studies with human participants with a confirmed diagnosis of ERS. Articles will be screened in two stages (ie, initially by title and abstract screening and then full-text screening by two independent reviewers). Data extraction will be conducted using a customized electronic data extraction form. We will provide a narrative synthesis of the findings from the included studies. We will structure the results according to themes. RESULTS: This protocol is registered with the Open Science Framework. The electronic search was conducted in July 2020 and updated in April 2021. The research findings will be published in an open access journal. CONCLUSIONS: Dentists should be able to identify patients with clinical features of ERS so that they receive appropriate referrals for renal evaluation, genetic counseling, and oral rehabilitation to increase the patient's quality of life. A scoping review is the most appropriate method to conduct this comprehensive exploration of the current evidence, which may be sparse due to the rarity of the condition. It will also enable us to identify gaps in the research. TRIAL REGISTRATION: Open Science Framework; https://osf.io/cghsa. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29702.

Taurodontism in dental genetics.

Taurodontism is a dental anomaly defined by enlargement of the pulp chamber of multirooted teeth with apical displacement of the pulp floor and bifurcation of the roots. Taurodontism can be an isolated trait or part of a syndrome. A study was conducted to document the dental and craniofacial aspects of genetic thin bone disorders in South Africa. Sixty-four individuals with Osteogenesis imperfecta (OI), one individual with Pyle disease and one with Torg-Winchester syndrome respectively, were assessed clinically, radiographically and at a molecular level. Ten patients with OI XI and those with Pyle disease and Torg-Winchester syndrome had taurodontism. Taurodontism has been identified in several genetic disorders necessitating cognizance of the possible existence and implications of this characteristic when managing patients in the dental environment. Further studies should be directed toward identifying the incidence, etiology, and molecular pathways leading to taurodontism and its relationship to genetic syndromes.

Gordon syndrome: Dental implications and a case report.

AIM: This article describes the craniofacial and dental features of an individual with Gordon syndrome. The dental management implications and considerations of treating patients with Gordon Syndrome and similar conditions resulting in limited mouth opening are discussed. METHODS: A 14-year-old South African male was referred to the Dental Genetics Clinic with the main complaint of carious teeth. His craniofacial characteristics included low set and posteriorly rotated ears, down-slanted palpebral fissures, sloping shoulders, and a broad neck. A prognathic mandible and mild facial asymmetry were noted. He had a significant limitation of mouth opening (2 cm at incisors). Radiographic examination revealed multiple carious teeth, missing mandibular premolars, impacted maxillary premolars, taurodontism of the 44 and 34, and enlarged coronoid processes of the mandible. Dental extractions and restorations have been performed under local anaesthesia. CONCLUSION: Gordon syndrome and similar conditions, may result in limited oral opening and impaired manual dexterity. The severity of limitation of mouth opening determines management. Dental management should focus on ensuring that the patient is able to maintain good oral hygiene by customising homecare for the individual and regular dental visits.

MACRODONTIA: A brief overview and a case report of KBG syndrome.

Macrodontia is a dental condition where a tooth or group of teeth are abnormally larger than average. Functional and aesthetic discrepancies may arise in affected individuals resulting in lowering the quality of life. It has been noted that macrodontia is associated with several genetic and endocrine abnormalities. Among which, KBG syndrome is a rare genetic disorder characterized by developmental and dental abnormalities. This case report provides a brief overview of the significance of macrodontia, along with presenting a case of KBG syndrome with atypical features in a South African, 16-year-old female. The dental manifestations are often overshadowed by other more conspicuous and complex syndromic features. Recognition of both the clinical and oral changes that occur in KBG syndrome facilitates accurate diagnosis and appropriate management of this condition. The authors highlight the importance for clinicians to be cognizant of the clinical implications of macrodontia.

Sella turcica morphology in patients with genetic syndromes: A systematic review.

The sella turcica is an important anatomical reference used in orthodontics for the evaluation of craniofacial growth. Studies have found variations in the sella turcica morphology in patients with syndromes affecting the craniofacial complex. This review aims to determine whether genetic syndromes involving the craniofacial complex are associated with abnormal radiographic sella turcica morphology and whether there is a pattern of malformation which is consistent within each syndrome. An electronic database search was conducted to identify relevant studies. We included primary studies describing the morphology of the sella turcica on lateral radiographs in human subjects with genetic syndromes involving the craniofacial complex. No restrictions were placed on language or timeframe. PROSPERO registration CRD42019148060. Thirty-eight studies were included in this review. A 'J'-shaped sella was found in patients with Hutchinson-Gilford-Progeria syndrome and other syndromes. A bulbous dorsum sellae was highly prevalent Cleidocranial dysplasia, and a bulbous dorsum sellae and uneven contours of the clivus was found in Cri du chat syndrome. A steep clivus was described in patients with Axenfeld-Rieger syndrome. An oblique anterior wall was the most frequent malformation found in Down's syndrome. Genetic syndromes affecting the craniofacial complex are associated with abnormal morphology of the radiographic sella turcica. Clinicians should be observant of abnormal sella turcica morphology which can be a sign of undiagnosed or subclinical syndromes. More high-quality studies are needed which use standardized and objective methods of determining the morphology of the sella turcica.

The evolution of the nosology of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a relatively common genetic skeletal disorder with an estimated frequency of 1 in 20 000 worldwide. The manifestations are diverse and although individually rare, the several different forms contribute to the production of a significant number of affected individuals with considerable morbidity and mortality. During the last decade, there have been extensive molecular investigations into the etiology of OI and these advances have direct relevance to the medical management of the disorder, and the purpose of this review is to document the history and evolution of the nosology of OI. The current nosology, based on molecular concepts, which are crucial in the identification of genotype-phenotype correlations in persons with OI, is also outlined. The successive revisions of the nosology and classification of OI have highlighted the importance of the nomenclature of the condition in order for it to be recognized by clinicians, scientists and patient advocacy groups. In this way, improved counseling of patients and individualized, tailored therapeutic approaches based on the underlying pathophysiology of the individual's type of OI have been facilitated.

Sella Turcica Morphology in Patients With Genetic Syndromes: Protocol for a Systematic Review.

BACKGROUND: The sella turcica is an important anatomical reference used in orthodontics and the evaluation of craniofacial growth. Studies have found an association between variations in sella turcica morphology in patients with certain syndromes affecting the craniofacial complex. It is hypothesized that each related syndrome or pathological condition is associated with a specific pattern of malformation of the sella turcica. OBJECTIVE: This study outlines the protocol for a systematic review that aims to determine if genetic syndromes involving the craniofacial complex are associated with abnormal radiographic sella turcica morphology and if there is a pattern of malformation that is consistent with each syndrome. METHODS: An electronic database search was conducted using a planned search strategy to identify relevant studies. We included primary studies evaluating the morphology of the sella turcica based on imaging from a lateral view. Specifically, only studies with postnatal human participants with genetic syndromes involving the craniofacial complex were included in this review. We placed no restrictions on the language or time frame of these studies. Based on the search findings, studies were further screened for relevance and eligibility by two independent reviewers. Data were extracted from the selected studies. We assessed the selected studies for risk of bias and quality by using risk of bias tools from the Joanna Briggs Institute. We will provide a narrative synthesis of our findings and a structured summary based on prespecified themes. RESULTS: The protocol is registered with PROSPERO (#CRD42019148060) and approved by the University of Western Cape Biomedical Science Research Ethics Committee (BM205/3). The literature search was conducted in September 2019 and updated in July 2020. The study was completed in August 2020, and the findings will be published in an open-access journal. CONCLUSIONS: The results of this systematic review are expected to provide a comprehensive list of morphological variations of the sella turcica, which will aid in the identification of syndromes associated with the craniofacial complex. We also expect to identify patterns of sella turcica morphology that highlight genotype-phenotype correlations, thus adding to the body of evidence relating to genetics and craniofacial malformations. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42019148060; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148060. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/16633.

CHARGE syndrome: genetic aspects and dental challenges, a review and case presentation.

BACKGROUND: CHARGE syndrome (CS) is a rare genetic condition (OMIM #214800). The condition has a variable phenotypic expression. Historically, the diagnosis of CHARGE syndrome was based on the presence of specific clinical criteria. The genetic aetiology of CS has since been elucidated and attributed to pathogenic variation in the CHD7 gene (OMIM 608892) at chromosome locus 8q12. CASE PRESENTATION: A South African female of mixed ancestry heritage, aged 4 years, was referred for dental assessment to the Faculty of Dentistry, University of the Western Cape, in 2018. She had a diagnosis of CHARGE syndrome confirmed by a Medical Geneticist from the Division of Molecular Biology and Human Genetics at the University of Stellenbosch. The patient had a long prior history of health and developmental problems, with the correct diagnosis becoming apparent over time. She presented with many oral and craniofacial features warranting consideration by the dentist including micrognathia, hypoplastic nasal bones, cranial nerve dysfunction, bruxism, craniofacial anomalies and compromised sensory perception. The treatment was mainly preventive and, although she fed through a percutaneous endoscopic gastrostomy tube (PEG), maintenance of her oral hygiene was necessitated. CONCLUSION: CS is a multisystem condition and the optimal care for an individual is with a specialist multidisciplinary team. The numerous systemic problems affecting these individuals take precedence in their care, and often there is neglect of their dental concerns. Given the abnormalities frequently present in the oral and craniofacial region, the authors recommend that a team of dental and other medical specialists be involved in the management of individuals with CS.

Use of flow cytometry in the phenotypic diagnosis of hodgkin's lymphoma.

Hodgkin's lymphoma (HL) has a unique immunophenotype derived from immunohistochemistry (positive for CD15, CD30, and Pax-5; negative for CD3, CD20 in most cases, and CD45). The knowledge gained over recent years enables better diagnosis, prognosis, and treatment of HL. Flow cytometry as a tool for the diagnosis of classic HL has not been useful in the past due to the difficulty in isolating Reed-Sternberg cells as they are admixed in a rich inflammatory background which consists mainly of T cells, B cells, eosinophils, histiocytes, and plasma cells. However, in the recent past, several studies have tried to identify Reed-Sternberg cells using flow cytometry on fine needle aspiration or tissue biopsy of lymph nodes to confirm or supplement immunohistochemistry staining in diagnosis. Newer and more sensitive tools such as flow cytometry can be used for diagnosis, technology that may have been difficult in the past for diagnosis of this lymphoma subtype. Using flow cytometry, diagnosis is faster and could lead to point-of-care technology especially where we have typical immunophenotype signatures. © 2018 International Clinical Cytometry Society.

Hodgkin's lymphoma and its association with EBV and HIV infection.

Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis. The present paper discusses the role of viral infection in African countries, as HL is considered to be a malignant disease characterized by an inflammatory reaction to an aberrant B cell clone that is well known as the Reed-Sternberg cell (HRS).

Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10.

BACKGROUND: A relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment. OBJECTIVE: To delineate the molecular basis for the condition. METHODS: Molecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population. RESULTS: Following polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation. CONCLUSION: The burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.

Craniofacial manifestations in osteogenesis imperfecta type III in South Africa.

OBJECTIVES: Osteogenesis imperfecta type III (OMIM 259420) is a severe autosomal recessive disorder. Affected individuals have multiple fractures, develop limb deformities with spinal malalignment and stunted stature. MATERIALS AND METHODS: The frequency of Osteogenesis imperfecta type III (OI III) is relatively high in the indigenous Black African population of South Africa. A review of the literature revealed a paucity of information regarding the craniofacial manifestations of the disorder in this ethnic group. The findings in 64 affected persons are documented. RESULTS: These abnormalities are related to the abnormal bone matrix which results in a deformed skull and dental malocclusion. The physiological process of swallowing may be an aetiological factor in the progressive development of a flattened palate. Mild changes in the shape of the head of the mandibular condyle and a lack of cortical bone on the joint surfaces were observed on cone beam computed tomography (CBCT) images. Affected persons had marked variations in the paranasal sinuses, including sinus hypoplasia and partial opacification. Cranial base anomalies were diagnosed from cephalometric radiographs and lateral skull radiographs. Platybasia and a 'J' shaped sella turcica were observed. CONCLUSION: The craniofacial abnormalities emphasize the importance of a raised level of awareness in terms of dental management and the challenges.