Dental Anomalies: Genetics

Abstract

Development of teeth is under strict genetic control, which ensures the formation and renewal of a certain number of teeth with specific shapes and positions in a reproducible timetable. Gene mutations can disturb normal dental development and affect tooth number, shape, eruption or formation of the hard tissues, enamel, dentin or cementum. These anomalies are often observed as isolated, that is, only dentition is affected, and especially failure to develop all teeth, tooth agenesis or hypodontia is extremely common. Different dental anomalies are also observed in numerous rare developmental syndromes because the genes and genetic networks that regulate tooth morphogenesis and differentiation are also active in the development of other organs and tissues. Tooth anomalies are especially associated with other ectodermal defects and orofacial clefts. Many examples indicate that teeth are often most sensitive to a reduced activity of a specific genetic pathway which is related to the complexity and self‐organising features of dental development.

Key Concepts:

  • Teeth are specialised ectodermal organs.

  • Development of dentition is regulated by cell interactions by same signalling pathways that are active in other organs and requires modulation of signalling by antagonist factors.

  • Tooth agenesis (failure to develop all teeth) is one of the most common developmental anomalies.

  • Most cases of tooth agenesis and supernumerary teeth are caused by reduced rather than complete inactivation of gene activity.

  • Dental anomalies are often diagnostic indications of a heritable syndrome or systemic disease.

  • Dental hard tissues do not regenerate after an injury and their development involve unique mechanisms.

  • Studies into congenital enamel defects are revealing functions for novel proteins that are involved in cellular regulation in ameloblasts and other cells.

Keywords: tooth agenesis; hypodontia; oligodontia; ectodermal dysplasia; cleft lip; cleft palate; enamel; dentin; tooth eruption

Figure 1.

Schematic presentation of genetic regulation of early tooth morphogenesis. Signalling molecules mediate cellular communication within and between the epithelium and the mesenchyme (epithelial signals, upper arrows; mesenchymal signals, lower arrows). The signals belong to conserved families that regulate the development of practically all tissues and organs (BMP, bone morphogenetic protein; FGF, fibroblast growth factor; SHH, sonic hedgehog; and WNT, homologues of Drosophila Wingless). Placodes and enamel knots are signalling centres in the epithelium which express locally more than 10 different signals regulating morphogenesis. Inactivation of the function of many different genes in mice leads to an arrest in tooth development at a specific stage, and their expression is typically regulated by the signals. Mutations in several of these genes have been shown to cause dental anomalies in humans.

Figure 2.

Radiographs and photographs of dentitions with tooth agenesis or supernumerary teeth. Asterisks mark the missing teeth. (a) Dentition with the common incisor–premolar hypodontia. Mandibular (lower) second premolars and maxillary (upper) right third molar (wisdom tooth) are missing. (b) Dentition with the common incisor–premolar hypodontia. Maxillary lateral incisor on the left side is missing and the one on the right side is peg shaped (arrow). Reproduced with permission from Nieminen . (c) An example of severe taurodontia (apical displacement of the root bifurcation) in molars (arrows). (d) Oligodontia caused by a mutation in PAX9. Missing permanent and second deciduous molars in a 7‐year‐old boy. Also, three of the second premolars as well as the upper lateral incisors are missing. (e) Oligodontia caused by mutations (compound heterozygote) in WNT10A. 15 permanent teeth are missing and the maxillary lateral incisor is peg shaped (arrow). Deciduous maxillary right canine and mandibular incisors and canines are retained at the age of 13 years. (f) Dentition of a boy with HED/EDA. Most of the permanent teeth are congenitally missing. Reproduced with permission from Nieminen . (g) Dentition of a patient diagnosed with Rieger syndrome. Nine permanent teeth are missing and the deciduous upper central incisors persist. Maxillary lateral incisors are peg shaped (arrows). (h) Supernumerary incisor, mesiodens, in an inverted position between the maxillary central incisors of a 9‐year‐old girl (arrow). (i) Dentition in a 15‐year‐old girl with cleidocranial dysplasia. Supernumerary teeth were depicted with arrows. (a), (b), (e), (f), (g) and (i) Courtesy of Sirpa Arte, (c) courtesy of Tiina Kuittinen, (d) courtesy of Satu Alaluusua, (h) courtesy of Ulla‐Maija Wesander.

Figure 3.

Radiographs and photographs of aberrations of dental hard tissues. (a) Panoramic tomogram of the dentition of a 12‐year‐old girl affected by dentinogenesis imperfecta type II as a result of a mutation in DSPP. Tooth crowns have a bulbous shape as the cervical regions are constricted and the pulp chambers have been obliterated, that is, filled with mineralising dentin. Attrition is observed in several teeth (arrows). (b) Upper dentition of the previous patient. Enamel has chipped off in several teeth and severe attrition is evident. (c) Panoramic tomogram of the permanent right molars of a 22‐year‐old woman with dentin dysplasia type II. Only a typical thistle‐shaped pulp chamber remains. Reproduced with permission from Nieminen et al.. (d) Schematic presentation of the DSPP gene and the consequences of different types of mutations. Mutations concentrate in exon–intron boundaries and in the code for dentin phosphoptein (DPP). Black arrows and text denote dentinogenesis imperfecta II and blue arrows and text dentin dysplasia II. All types of mutations prevent export and secretion of the DSPP protein. (e) AI, X‐linked hypoplastic type with hypoplastic stripes in the enamel of a 17‐year‐old girl. (f) AI, hypomaturation type. Teeth of an 11‐year‐old girl have a chalky opaque appearance. (g) AI, hypocalcified type. Teeth of a 10‐year‐old girl have a brownish discolouration. (a), (b), (e), (f) and (g) courtesy of Satu Alaluusua, (c) courtesy of Sirpa Arte.

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Web Links

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Nieminen, Pekka(Mar 2013) Dental Anomalies: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006088.pub2]