Familial Aggregation of Maxillary Lateral Incisor Agenesis rEsEArcH rEPOrts

In spite of recent developments, data regarding the genes responsible for the less severe forms of hypodontia are still scarce and controversial. This study addressed the hypothesis that agenesis of maxillary lateral incisors (MLIA) is a distinct type of hypodontia, by evaluating its familial aggregation and the occurrence of other types of ageneses or microdontia in probands’ relatives. Sixty-two probands with MLIA were identified, and information was collected on 142 first-degree relatives. Relative risk (RR) was calculated and compared by re-assessment of data previously published for the Swedish, Utah, and Israeli populations, for the same trait. A RR of 15 was obtained in the Portuguese, 16 in the Swedish, 12 in Utah, and 5 in the Israeli population. Our results support a significant familial aggregation of MLIA, show that MLIA almost never segregates with other forms of agenesis, and suggest that microdontia of maxillary lateral incisors is part of the same phenotype. KEY WOrDs: hypodontia, microdontia, maxillary lateral incisors, relative risk, familial aggregation. IntrODuctIOn Agenesis of maxillary lateral incisors (MLIA) and mandibular second premolars is the most frequent form of hypodontia, its frequency varying across populations (Grahnén, 1956; Horowitz, 1966; Alvesalo and Portin, 1969; Muller et al., 1970; Thilander and Myrberg, 1973; Magnusson, 1977; Rolling, 1980; Aasheim and Øgaard, 1993; Johannsdottir et al., 1997; Tavajohi-Kermani et al., 2002; Polder et al., 2004). Values between 0.8 and 4.25% have been found for MLIA in permanent teeth. In the Portuguese population, MLIA prevalence was estimated at 1.3% (Pinho et al., 2005). In spite of recent progress, the etiopathogenesis of hypodontia is largely unknown, although there is strong support for the hypothesis of a genetic etiology. There is evidence showing that congenital tooth absence can be the result of environmental or hereditary causes, or their interaction (Vastardis, 2000). Grahnén’s study (1956) in the Swedish population confirmed the hypothesis of a genetic component for hypodontia and attempted to clarify its modes of inheritance. Familial segregation studies suggested that hypodontia showed an autosomal-dominant inheritance in some families, with incomplete penetrance and variable expressivity (Grahnén, 1956; Svinhufvud et al., 1988; Vastardis et al., 1996; Arte et al., 2001); however, modes of transmission linked to the X-chromosome and of polygenic or multifactorial type have also been proposed (Chosack et al., 1975). Grahnén (1956) and Alvesalo and Portin (1969), among others, strongly suggested that peg-shaped incisors are a variable expression of the gene responsible for MLIA, an argument also presented by Arte et al. (2001). Woolf’s study (1971) focused only on MLIA. The identification of phenotypes of tooth absence and hypoplasia in mouse lines null-zygous for different genes, together with the identification of mutations causing hypodontia in a relatively small number of human families (Vastardis et al., 1996; Stockon et al., 2000; van den Boogaard et al., 2000; Nieminen et al., 2001; Frazier-Bowers et al., 2002; Mostowska et al., 2006; Kapadia et al., 2006; Tao et al., 2006; Tarpey et al., 2007), confirmed the relevance of genetic determination of tooth agenesis. However, the role of genes in sporadic and less severe forms of hypodontia has not yet been clarified. Additionally, there is evidence for an extensive clinical and genetic heterogeneity within the “hypodontia” phenotype. Further definition of clinical and genetic subtypes within hypodontia is thus required, and familial aggregation studies are needed to establish a measure of the genetic contribution to different subtypes of congenital tooth absence, as well as their modes of inheritance–a first step toward the identification of causative genes. Familial Aggregation of Maxillary Lateral Incisor Agenesis rEsEArcH rEPOrts clinical JDR OnlineFirst, published on April 16, 2010 as doi:10.1177/0022034510364486