Hypodontia is defined as the developmental absence of one or more teeth excluding the third molars. It is one of the most common dental anomalies, and can have a negative impact on function, and also appearance. It rarely occurs in primary teeth (also known as deciduous, milk, first and baby teeth) and the most commonly affected are the adult second premolars and the upper lateral incisors. It usually occurs as part of a syndrome that involves other abnormalities and requires multidisciplinary treatment.
The phenomenon can be subdivided into the following according to the number of teeth concerned: Hypodontia: one to six missing teeth excluding the third molars Oligodontia: six or more missing permanent teeth excluding the third molars Anodontia: complete absence of teeth
Signs and symptoms Typically, all baby teeth will be present by the age of three. As for all adult teeth, they erupt between the ages 6 to 14, with the exception of the third molar, also known as the wisdom teeth which normally erupt between 17 and 25 years of age. If the tooth has yet to erupt by an appropriate age, panoramic x-rays are taken.
Dental features Microdontia may be present in one or more of the other teeth. This means that the teeth appear smaller than normal, may be observed in both the primary and permanent dentition. This condition can be genetically-linked and in severe cases, may present themselves in the form of ectodermal dysplasia, cleft lip or palate or Down syndrome. A delay in tooth development may also serve as an indication, whereby the absence of an adult successor slows down the normal resorption of the roots of the baby teeth, which is the progressive loss of parts of the tooth.
Misplaced (ectopic) positioning of the adult teeth may be discovered upon examination or a radiograph. One of the consequences may be an adult tooth intercepting with a baby tooth, causing premature loss or wrong positioning. This can be due to either the absence of neighboring teeth acting as a guide during eruption or the lack of space in the jaw for them to erupt into because of malocclusion.
Skeletal features Several studies have discovered that anteriorly missing teeth can accompany retrognathic maxilla, also known as an underbite, prognathic mandible, where the lower jaw protrudes out more than normal, and smaller posterior cranial base length. Occurrence of hypodontia can be associated with reduced anterior lower facial height and lip protrusion. This can be linked to lower maxillary to mandibular plane angles.
A more acute mandibular angle and flatter chin may develop as a result. These characteristics become more prominent as the condition becomes progressively severe, particularly when more than one tooth is missing.
Other dental and radiographic features Data derived from principal component analysis of radiographic images show that children with mild hypodontia may display significant increase of the interincisal angle and decrease in the maxillary and mandibular incisor angles.
Cephalometric tracing is commonly used to study a patient's dentofacial proportions in the craniofacial complex. This can aid in predicting growth changes, allowing dentists, especially orthodontists, to develop a suitable treatment plan. Coupled with that, findings consistent among individuals include: Anterior hypodontia associated with hyper divergent craniofacial pattern; A tendency toward a class III malocclusion identified in maxillary hypodontia, and; Reduced lower posterior facial height in children with posterior and mandibular hypodontia.
Associated anomalies
Reduction in coronal or radical dimensions Retained primary teeth Ectopic canine eruption Abnormal morphology such as peg-shaped maxillary lateral incisors and taurodontism, characterized by an enlarged tooth body and roots that are reduced in size Extracted teeth
Cause Several theories regarding the aetiology of hypodontia have been proposed in existing literature. There have been various theories mostly looking into genetic and environmental aspects and how they may both be involved. However, the exact cause remains unclear. The extent of individual influences of genetic and environmental factors is still widely debated.
Theories regarding the mechanism through which hypodontia occurs can be categorised into evolutional or anatomical.
Preliminary studies focused on an evolutionary approach which suggested shortening of the intermaxillary complex and thus shorter arches may contribute to a decrease in number of teeth. This was also suggested in 1945 by Dahlberg using Butler's Field Theory that focused on evolution and development of mammalian teeth into human dentition in an attempt to analyse different of agenesis. In each jaw, four morphological sites were identified (incisors, canines, premolars and molars). The tooth at the end of each region was less genetically stable and hence more prone to absence. In contrast, the tooth most mesial in each region seemed to be more genetically stable. A subsequent theory hypothesised the teeth at the end of each region were possibly "vestigial bodies" that became obsolete during the evolutionary process. At present, it has been theorised that evolutionary change is working to decrease the human dentition by the loss of an incisor, premolar and molar in each quadrant. According to Vastardis (2000), the size of jaws and number of teeth seem to decrease along with human evolution.
Theories focusing on anatomical principle, hypothesised that specific areas of the dental lamina are especially prone to environmental effects during tooth maturation. Svinhufvud et al. (1988) suggested that teeth that were more prone to absence developed in areas of initial fusion of the jaw. For instance, maxillary lateral incisors originate where the lateral maxillae and medial nasal bone processes fuse. In contrast, Kjaer et al. (1994) suggested regions where innervation developed were more sensitive than areas of fusion. Commonly affected regions were found to undergo innervation last, this might imply the developmental relationship between nerve and hard tissue. It is thought to be local nerve development that affects tooth agenesis rather than global development, as brainstem anomalies have not been seen to affect tooth development.
Presently, the role of polygenic and environmental factors on hypodontia is recognised in most theories.
Environmental factors Environmental factors can be classified into two main groups, invasive and non-invasive. These factors act additively or independently, ultimately affecting positioning and physical development of the tooth.
Invasive environmental factors potentially affect tooth development and positioning leading to hypodontia and impaction. Examples include jaw fractures, surgical procedures and extraction of the preceding deciduous tooth. Treatment such as irradiation has been shown to have severe effects on developing teeth. In a smaller capacity, chemotherapy was also found to have a similar effect. Thalidomide (N-phthaloylglutamine) was also discovered to have a causative effect on mothers who took the drug during pregnancy, resulting in congenitally missing teeth in their children. A link was found between systemic diseases, endocrine disruption (i.e. idiopathic hypoparathyroidism and pseudohypoparathyroidism) and ectodermal dysplasia. However, a definite etiological relationship has yet to be established. Examples of infections include rubella and candida. Exposure to PCBs (such as dioxin), allergies, and toxic epidermal necrolysis following a drug reaction may also be contributing factors.
In a recent study assessing environmental risk factors for hypodontia, it was established that maternal smoking does play a causative role in hypodontia. Passive smoking and caffeine were also assessed but showed no statistical significance.
The Journal of the American Dental Association published preliminary data suggesting a statistical association between hypodontia of the permanent teeth and epithelial ovarian cancer (EOC). The study shows that women with EOC are 8.1 times more likely to have hypodontia than are women without EOC. The suggestion therefore is that hypodontia can serve as a "marker" for potential risk of EOC in women.
Genetics Genetic causes also involve the genes MSX1 and PAX9.
Genetic associations for selective tooth agenesis ("STHAG") include:
Type OMIM Gene Locus STHAG1 MSX1 4p16 STHAG2 ? 16q12 STHAG3 PAX9 14q12 STHAG4 WNT10A 2q35 STHAG5 ? 10q11 STHAG6 LTBP3 11q12 STHAGX1 EDA Xq13.1
Failure of tooth formation due to disturbances during the early stages of development could be the cause of congenital missing teeth; this is also known as tooth agenesis. A variety of studies show that missing teeth are commonly associated with genetic and environmental factors. Some literature also shows that a combination of both factors may contribute to the occurrence of hypodontia.
Most craniofacial characteristics are influenced by both genetic and environmental factors through complex interactions. The variable expressivity of traits can be either completely genetically determined, environmentally determined, or both. That genetics plays an important role in hypodontia is shown in many different cases. There are hundreds of genes expressed and involved in regulating tooth morphogenesis. Although a single gene defect may contribute to hypodontia, more studies propose that hypodontia is the result of one or more points of closely linked genetic mutations, or polygenic defects.
The pattern of congenitally missing teeth seen in monozygotic twins is different, suggesting an underlying epigenetic factor, which may be due to the simultaneous occurrence of two anomalies. This multifactorial aetiology involves environmental factors which trigger the genetic anomalies, resulting in the occurrence of dental agenesis. Common environmental factors include infection, trauma and drugs which predispose to the condition. In hereditary cases, evidence of dental germ developing after surrounding tissues have closed the space required for development may be a large contributing factor, as well as such genetic disorders as Down syndrome, ectodermal dysplasia, cleidocranial dysplasia, and cleft lip and cleft palate.
MSX1 MSX1 (muscle segment homeobox 1) is involved in condensation of ectomesenchyme in the tooth germ. Among the members of homeobox genes, MSX1 and MSX2 are crucial in mediating direct epithelial-mesenchymal interactions during tooth development by expressing in regions of condensing ectomesenchyme in the tooth germ. MSX1 mutations have been identified as a contributing factor in missing second premolars, third molars, and a small percentage of first molars. MSX1 is less likely to cause anterior agenesis.
Heterozygous mutations in PAX9 (paired box gene 9) could arrest tooth morphogenesis as it plays a role of transcription the gene expressed in tooth mesenchyme at the bud stage during tooth development. A study showed that single nucleotide polymorphisms in PAX9 were highly associated with missing upper lateral incisors.
AXIN2 The AXIN2 (AXIS inhibition protein 2) gene is a negative regulator of the Wnt signalling pathway, which is important in regulating cell fate, proliferation, differentiation and apoptosis. Its polymorphic variant may be associated with hypodontia such as missing lower incisors or in a more severe form of agenesis like oligontia (lack of six or more permanent teeth).
EDA EDA provides instructions for making a protein called ectodysplasin A. It encodes transmembrane protein that is part of TNF (tumour necrosis factor) family of ligands. EDA gene defects cause ectodermal dysplasia, which is also known as X-linked hypohidrotic ectodermal dysplasia. Common dental features of ectodermal dysplasia are multiple missing teeth and microdontia.