Severe Hypodontia: Dental, Dentofacial, Osseous and Genetic Aspects

Severe Hypodontia: Dental, Dentofacial, Osseous and Genetic Aspects

SEVERE HYPODONTIA: DENTAL, DENTOFACIAL, OSSEOUS AND GENETIC ASPECTS Marijn Créton Promotoren: Prof.dr. M.S. Cune & Prof.dr. C. de Putter Colofon © Marijntje Annika Créton ISBN: 978-90-393-5807-8 Cover: Lay-out: Chris Bor, Medische Fotografie en Illustratie, AMC, Amsterdam Printed by: Buijten & Schipperheijn, Amsterdam SEVERE HYPODONTIA: DENTAL, DENTOFACIAL, OSSEOUS AND GENETIC ASPECTS Ernstige hypodontie: dentale, dentofaciale, osseale en genetische aspecten (with a summary in English) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op vrijdag 6 juli 2012 des ochtends te 10.30 uur door Marijntje Annika Créton geboren op 28 september 1973 te Utrecht Promotoren Prof.dr. M.S. Cune Prof.dr. C. de Putter Sponsoring Het drukken van dit proefschrift werd mede gefinancierd door: NVT - Nederlandse Vereniging voor Tandartsen www.nvt.nu NMT - Nederlandse Maatschappij tot bevordering der Tandheelkunde www.tandartsennet.nl NVGPT - Nederlandse Vereniging voor Gnathologie en Prothetische Tandheelkunde www.nvgpt.nl NVVRT - Nederlands Vlaamse Vereniging voor Restauratieve Tandheelkunde www.nvvrt.com BioComp Dental b.v. www.biocomp.eu Straumann B.V. www.straumann.nl Astra Tech Benelux BV www.astratech.com Tandtechnisch laboratorium Oosterwijk www.ttloosterwijk.nl Elysee Dental www.elysee-dental.com NVOI - Nederlandse Vereniging voor Orale Implantologie www.nvoi.nl Prof.dr. P. Egyedi Stichting Paranimfen: M.H. Créton Dr. R.J. Créton Manuscriptcommissie Prof.dr. WPTM Mali, röntgenoloog, UMC Utrecht, voorzitter Prof.dr. R Koole, kaakchirurg, UMC Utrecht Prof.dr. GJ Meijer, kaakchirurg, UMC St. Radboud, Nijmegen Dr. JK Ploos van Amstel, medisch geneticus, UMC Utrecht Prof.dr. AJP Schrijvers, UMC Utrecht Contents Chapter 1 9 General introduction and aims of the study General introduction General aims of the study Specific aims of the study: questions of investigation Chapter 2 29 Patterns of missing teeth in a population of oligodontia patients Chapter 3 41 Dentofacial characteristics of patients with hypodontia Chapter 4 61 Radiographic features of mandibular trabecular bone structure in hypodontia Chapter 5 75 Implant treatment in patients with severe hypodontia: a retrospective evaluation Chapter 6 91 Three-dimensional analysis of tooth dimensions in the MSX1-missense mutation. Chapter 7 109 Mutations in WNT10A are present in more than half of isolated hypodontia cases Chapter 8 131 General discussion and future perspectives General discussion Future research Summary 147 (Dutch summary) Dankwoord 163 Curriculum Vitae 169 Appendix I 173 The Dutch hypodontia database Appendix II 179 Full-Mouth Tooth Agenesis Code in 106 oligodontia patients Appendix III 185 Restorative aspects: clinical decision-making General introduction and 11 aims of the study General introduction The number of teeth is commonly used as an important indicator for oral health. Already in 1992 the World Health Organization has proclaimed that one of their goals for the year 2000 was that people should have a functional, esthetic dentition of at least 20 teeth throughout life and can go without some sort of dental prosthesis.1 This is not just a challenge for underdeveloped countries and an ambitious goal, also considering the fact that in the Chapter 1 Chapter year 1992 an estimated 23% of the Dutch population was fully edentulous in the maxilla and/or mandible. Although this number is rapidly declining, in the years 2000 and 2009 the corresponding numbers were still approximately 16% and 12%, with marked regional and decreasing gender differences (Statline, CBS, 2010).2 11 Most of these patients will have had a full natural dentition at one moment in time and have and aims of the study General introduction lost their teeth because of caries and / or periodontal disease. However, this is not as obvious as it may seem. In some cases teeth may not have developed properly and have been absent from birth. The process of tooth development is called odontogenesis. Odontogenesis is quite a complex process. It consists of a series of events by which teeth develop from embryonic cells that derive from mesenchymal and epidermal tissues and subsequently grow, before erupting into the mouth. Tooth development resembles the development of other organs such as glands and hair, both morphologically and molecularly. Odontogenesis and more specifically tooth morphogenesis (its shape) is regulated through a large number of molecules that are organized in signaling networks.3 These molecules initiate reciprocal interactions between epithelial and mesenchymal cells that cause the ectoderm to thicken, tooth buds to grow and fold and eventually form the complex shape of a tooth crown.4 The study of these processes is the domain of expertise of developmental biologists. Their field is growing rapidly and new technologies emerge on a constant basis, helping us understand how dental abnormalities come about, and in the future may even help us to grow teeth.5, 6 Because of the many factors involved, odontogenesis is a rather precarious process that can easily be disturbed and disrupted as a result of various endocrine, local, environmental and genetic factors.3 An endocrine, hormonal cause for hypodontia is for example idiopathic (hypo) parathyroidism.7 Trauma or cysts in the apical area of the alveolar process are considered local causes.8 Environmental factors include virus and yeast infections (i.e. Rubella9 and Candida), exposure to certain toxins (i.e. dioxin)10, and radio- and chemotherapy during childhood. For example, nearly all patients from a Dutch population of 40 who underwent allogenic hematopoietic stem cell transplantation for hematological malignancies developed dental disturbances, especially those who were younger than 3 years of age when treatment commenced.11 Also, 50% of surviving children with a rhabdomyosarcoma who had radiation 12 Figure 1 The genetic factors that disturb odontogenesis are comprehensive and mutations in a large and rapidly growing number of genes have been identified as the causes of dental abnormalities such as amelogenesis imperfecta. Amelogenesis imperfecta is a hereditary condition in which the dental enamel does not develop properly in the whole dentition. In this case, the poor condition of the enamel caused chipping with the lower molars and bad esthetics for the front teeth. therapy to the head or neck during childhood present with dental abnormalities.12 It is hard to distinguish between the original illness and the therapeutic measures as the actual cause of the dental sequelae. The genetic factors that disturb odontogenesis are comprehensive and mutations in a large and rapidly growing number of genes have been identified as the causes of dental abnormalities such as amelogenesis and dentinogenesis imperfecta (figure 1), dentin dysplasia’s and anomalies of teeth number.6, 13-15 The latter is the general topic of this thesis and will be discussed in more detail. Numerical anomalies in tooth development: hyperdontia and hypodontia With respect to numerical anomalies in tooth development a distinction between hyper- and hypodontia can be made, either in combination with or not in combination with a syndrome. Hyperdontia (ICD-10: K00.1) occurs singly, in multiples, unilaterally or bilaterally, in the maxilla, in the mandible or both. It has a prevalence in the permanent dentition that varies from 0.1 – 3.8 %, depending on the population studied.16 The most common presentation of hyperdontia is the so-called mesiodens; an extra, peg-shaped tooth that is commonly located between the 2 maxillary central incisors. Extra teeth in the molar area are called paramolar teeth, those located posterior to the third molar are referred to as distomolar teeth. Although cases of multiple supernumerary teeth have been reported they are rare and seldom seen without associated diseases or syndromes caused by genetic disturbances such as Gardner’s syndrome (APC gene), cleidocranial dysostosis (RUNX2 gene) and tricho- a Chapter 1 Chapter b 13 General introduction and aims of the study General introduction c Figure 2a A supernumerary permanent mandibular incisor is a rare finding (2a). b-c A super- numerary right lateral incisor is relatively more common. rhino-phalangeal syndrome (TRPS1 gene).8, 16, 17 In uncommon cases ‘extra’ teeth or tooth like structures can develop outside the mouth (i.e. in the ovaries, lungs or orbit). They are referred to as teratomas. Subjects with supernumerary teeth generally have larger teeth (macrodontia) than controls.18-20 Restorative treatment is usually uncomplicated and may consist of extraction of the supernumerary teeth, although on occasions they fit in reasonably well in the dental arch (figure 2a-c). Hyperdontia falls beyond the scope of this thesis. Hypodontia (ICD-10: K00.0), the congenital absence of one or more permanent teeth, is the most common developmental anomaly in man. It has a prevalence of 5.5% in Europeans, with a preference for women compared to men (1.37:1).21 There are racial differences with 14 respect to the prevalence of hypodontia. In the Caucasian race the second mandibular bicuspid and maxillary lateral incisor are the most common absent tooth type, whereas in Asians the first mandibular incisor is the most frequently congenitally absent tooth.22 In case of anodontia all permanent teeth are missing, which is extremely rare. By definition,

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