Displasia ectodérmica hipoidrótica é uma doença genética rara, clinicamente caracterizada por alterações envolvendo os dentes, pele e suas estruturas anexas. Manifestações orais comuns incluem anadontia ou oligodontia, dentes conóides e xerostomia. Poucos relatos associam displasia ectodérmica e redução do fluxo salivar. O objetivo desse estudo é analisar possíveis alterações nas glândulas salivares de dez portadores de displasia ectodérmica que fazem acompanhamento no Departamento de Dermatologia Pediátrica da Universidade de São Paulo. Ultrassonografia foi realizada em dez casos em infantes portadores de displasia ectodérmica hipoidrótica nas suas glândulas salivares parótida e submandibular. Três apresentaram alterações na glândula parótida e/ou submandibular. Aplasia ou hipoplasia das glândulas salivares maiores é associada a casos de displasia ectodérmica e sugere-se acompanhamento rotineiro das glândulas salivares maiores usando ultrassonografia para prevenção de alterações decorrentes da hiposalivação na cavidade oral. / Background- Hypohidrotic ectodermal dysplasia is a rare genetic disease, clinically characterized by defects involving skin and their adnexal structures, as well as oral structures such as teeth, and occasionally salivary glands. These latter manifestations include anodontia or hypodontia, conical teeth and xerostomia. Objective- To analyze possible alterations in major salivary glands of ten patients with ectodermal dysplasia, using image exam. Methods- Ultrasonography was performed in ten pediatric cases of hypohidrotic ectodermal dysplasia to investigate the status of parotid and submandibular salivary gland. Results- Three patients presented aplasia/hypoplasia of at least one gland examined. The other 7 patients did not present any alterations in parotid and submandibular glands. Limitations- Although ultrasonography exam is adequate to investigate the presence and status of major salivary glands, other important glands such as sublingual and minor mucous salivary glands are not well-visualized using this technique. Conclusions- Aplasia or hypoplasia of the major salivary gland is strongly related to ectodermal dysplasia and we suggest routine evaluation of the major salivary gland using ultrasound to monitor and manage the possible impact of xerostomia in oral health.

Displasia ectodérmica hipoidrótica é uma doença genética rara, clinicamente caracterizada por alterações envolvendo os dentes, pele e suas estruturas anexas. Manifestações orais comuns incluem anadontia ou oligodontia, dentes conóides e xerostomia. Poucos relatos associam displasia ectodérmica e redução do fluxo salivar. O objetivo desse estudo é analisar possíveis alterações nas glândulas salivares de dez portadores de displasia ectodérmica que fazem acompanhamento no Departamento de Dermatologia Pediátrica da Universidade de São Paulo. Ultrassonografia foi realizada em dez casos em infantes portadores de displasia ectodérmica hipoidrótica nas suas glândulas salivares parótida e submandibular. Três apresentaram alterações na glândula parótida e/ou submandibular. Aplasia ou hipoplasia das glândulas salivares maiores é associada a casos de displasia ectodérmica e sugere-se acompanhamento rotineiro das glândulas salivares maiores usando ultrassonografia para prevenção de alterações decorrentes da hiposalivação na cavidade oral. / Background- Hypohidrotic ectodermal dysplasia is a rare genetic disease, clinically characterized by defects involving skin and their adnexal structures, as well as oral structures such as teeth, and occasionally salivary glands. These latter manifestations include anodontia or hypodontia, conical teeth and xerostomia. Objective- To analyze possible alterations in major salivary glands of ten patients with ectodermal dysplasia, using image exam. Methods- Ultrasonography was performed in ten pediatric cases of hypohidrotic ectodermal dysplasia to investigate the status of parotid and submandibular salivary gland. Results- Three patients presented aplasia/hypoplasia of at least one gland examined. The other 7 patients did not present any alterations in parotid and submandibular glands. Limitations- Although ultrasonography exam is adequate to investigate the presence and status of major salivary glands, other important glands such as sublingual and minor mucous salivary glands are not well-visualized using this technique. Conclusions- Aplasia or hypoplasia of the major salivary gland is strongly related to ectodermal dysplasia and we suggest routine evaluation of the major salivary gland using ultrasound to monitor and manage the possible impact of xerostomia in oral health.

La dysplasie ectodermique hypohidrotique liée à l’X (DEX) est consécutive à la mutation du gène Eda. Ce projet de recherche avait pour but d’étudier les dysmorphoses cranio-faciales chez le mutant murin Tabby représentant l’équivalent phénotypique de la DEX. La forme des mandibules en vue latérale a été étudiée à partir d’approches quantitatives associant μ-CT, traitement d’images, analyses de Fourier elliptique et analyses métriques. Une première étude ex vivo menée sur 39 spécimens Tabby et 35 souris wild-type adultes a permis de mettre en évidence un hypo-développement mandibulaire chez Tabby. Deuxièmement, une étude longitudinale in vivo de la croissance mandibulaire mise en place sur une cohorte de 23 individus (12 WT et 11 Tabby) a montré que les individus Tabby présentaient cet hypodéveloppement dès le 1er mois et qu’il se maintenait à la fin de la première année de vie. Les défauts du gène Eda affectent ainsi le développement de la mandibule en plus des dérivés ectodermiques. / The X-linked hypohidrotic ectodermal dysplasia (XLHED) is the result of Eda gene defect. This research project studied the cranio-facial dysmorphoses in Tabby murin mutant which having a similar phenotype to the XLHED. A association of mutiple quantitive approachs (μ-CT, images processing, elliptical Fourier analyse and metric analyses) permitted to study the mandible’s shape in a lateral view. A first ex vivo study led on 39 specimens Tabby and 35 WT mice allowed to highlight a mandibular hypodevelopment in Tabby. Secondly, a longitudinal in vivo study of mandibular growth, based on 23 specimen (12WT and 11 Tabby), showed that Tabby presented this hypodevelopment from the 1st month and that it remained at the end of the first year of life. The Eda gene affects the development of mandible and ectodermal structures.

La Dysplasie Ectodermique Hypohidrotique liée à l'X (DEX) est une maladie génétique liée à une mutation du gène EDA. Le phénotype exprimé par le modèle murin Tabby est l'équivalent de celui observé dans l'espèce humaine et présente des anomalies dentaires, cranio-faciales, vertébrales et des défauts de trabéculation osseuse. Dans ce contexte, une cartographie de ces anomalies chez le mutant Tabby était nécessaire et l'analyse de l’impact de la mutation Eda/Ta sur la croissance du squelette crânien et post-crânien a été étudiée. Un suivi longitudinal d'une cohorte d'individus murin Tabby (5 mâles hémizygotes EdaTa/Y, 6 femelles hétérozygotes EdaTa/+) et sauvages (n=12) a été réalisé à partir d’une succession d’acquisitions TDM pendant plus de 2 ans. L'observation des profils de croissance et de leurs paramètres a montré des anomalies de croissance du complexe crânio-facial, de la base du crâne (hypo-développement crânien) et un déficit de croissance relatif des os longs (fémur et humérus) chez les souris hémizygotes EdaTa/Y. Ces résultats mettent pour la première fois en évidence des anomalies de développement des os longs et confirment le rôle d’EDA-A dans la formation normale du squelette. Ces données constituent un pré-requis essentiel pour tester l’efficacité de tentatives de réversion phénotypique à partir de protéines recombinantes. / X-linked Hypohidrotic Ectodermal Dysplasia (XLHED) is a genetic disorder due to a mutation of the EDA gene. The phenotype expressed by Tabby mice, murine model of XLHED, is equivalent to that observed in humans including dental anomalies, craniofacial and vertebral trabecular bone defects. In this context, a mapping of these anomalies in Tabby mice was necessary and the impact of the EdaTa mutation on cranial and post -cranial skeletal growth was studied. A 2 years (112 weeks) μCT follow-up of Tabby mice (5 hemizygous males EdaTa/Y, 6 heterozygous females EdaTa/+) and Wild Type group (n = 12) hasbeen performed. The observation of growth patterns and parameters showed a relative cranial hypodevelopment, abnormal growth of the craniofacial complex and a relative hypo-development of appendicular skeleton (femur and humerus) in Tabby mice. These results allowed for the first time to highlight appendicular developmental abnormalities, confirming the role of EDA-A in the normal formation of the skeleton. While enriching the phenotypic picture of this syndrome, in a therapeuticperspective, all of these data are an essential prerequisite to test the effectiveness of attempts to phenotypic reversion from recombinant proteins.

Doctor Scientiae (Odontology) - DSc(Odont) / Investigations of pathoses of the oral cavity encompass a relatively wide spectrum of diseases, abnormalities, tumours and tumour-like conditions affecting and occurring in the dental hard tissues and supportive structures, the bony skeleton of the face and the soft tissues of the. mouth. It involves a study of the normal - oral biology - and the abnormal - oral pathology. Oral pathology is a relatively new specialized field of dental science and practice. In South Africa, prior to the nineteen-fifties, research in oral pathology was primarily directed towards dental disease. Two people - Julius Staz of the University of the Witwatersrand and Tony Ockerse of the University of Pretoria - were the doyens in this field and made major contributions to dental science. Staz reported on the status of dental caries and tumorous malformations of teeth and Ockerse on the prevalence and severity of fluorosis in South Africa. During the fifties a second generation of dental surgeons, who were interested in soft tissue, bone and tumour pathology, emerged. They ,were Bertie Cohen, George Baikie, Mervyn Shear and John Lemmer who, at that time, were all from the University of the Witwatersrand. Bertie Cohen later joined the Royal College of Surgeons of England. Mervyn Shear led the field with his research on cysts of the oral cavity. The practice of oral pathology, moulded on anatomical pathology, was established in the early sixties and Mervyn Shear and the author, from the University of Pretoria, became known as oral pathologists. Research at that early stage comprised clinical and histological observations of oral lesions, diseases, tumours and tumour-like conditions. Observation techniques became more sophisticated during the sixties and seventies with the advent of histochemistry and electronmicroscopy. The next major development which blossomed in the seventies and early eighties was the application of epidemiological methods in the study of disease. Epidemiological principles enabled the correct recording of profiles of oral pathoses in the community. Much was learnt about the prevalence and distribution of oral conditions. The application and use of experimental models, especially laboratory animals, became popular in the eighties. Amongst others, a germfree animal unit was established in the Faculty of Dentistry of the University of Stellenbosch enabling workers to study the microbiological aetiology of dental and oral disease. Morphological observations of tumours and mucosal lesions were further enhanced during this period with the development of immunocytochemistry Experimental cell studies by means of cell culture techniques, commenced late in the eighties and was established in the early nineties. These models fostered molecular biology techniques which have become useful tools for the investigation of the aetiology of disease at a cellular and molecular level. At present molecular techniques are also popular in other spheres of oral pathology such as microbiological, immunological and oncological research. The author's first contact with oral pathology as a subject, forming an important and interesting part of dentistry, was the prescribed textbook "Oral and Dental Diseases", 2nd ed., 1951., by HH Stone of the University of Liverpool in the United Kingdom. Subsequently an enduring interest in the subject and research was cultivated by three teachers and colleagues, Ivor Kramer, Robert Bradlow and Mervyn Shear. Ivor Kramer, Professor of Oral Pathology in the Eastman Dental Institute of the University of London was a superb postgraduate teacher of oral pathology, and revelled in research. The Dean of the Institute, Professor Sir Robert Bradlow was a clinician and splendid diagnostician. He correlated the clinical and histopathological features of oral diseases. These two teachers set the course in oral pathology for the author during his postgraduate studies. In the sixties, after a spell at the University of Pretoria, the author joined Professor Mervyn Shear at the University of Witwatersrand. It was here that the author could further his skills of presenting lectures and research papers in an orderely manner and strengthen his love of research. The research carried out by the author reflects to a large extent the development of research in oral pathology in South Africa since 1960.. It includes studies of diseases and lesions of the oral mucosa, the dental hard tissues, tumours of the oral cavity and jaws and forensic odonto-stomatology. To date 139 articles have been published and accepted in scientific journals of which I was the first or co-author. The research presented here, however, comprises only those studies related to pathoses of the oral mucosa as it occurs in South Africa. Fifty-four papers and two abstracts are submitted. The papers are grouped into two divisions which include studies on (I) normal human oral and ectocervical mucosa and (II), those related to pathoses of the oral mucosa. The latter is subdivided into sections on: the profile of lesions of the oral mucosa in the community; cytological, clinical and morphological features of lesions of the oral mucosa; and studies on the aetiology of lesions of the oral mucosa. Each division and section is preceded by a declaration as to the contribution of the author or co-authors and a précis of the aims, objects and research findings. In the introduction of the précis statements are made explaining the aims of the study. These statements are not referenced because they appear in the respective articles.