Problems of Genetic Model Testing in Early Onset Periodontitis

Abstract

Familial aggregation of early onset or juvenile Periodontitis (JP), a disorder that varies in expression and age of onset, has been recognized for some time. Autosomal recessive and X‐linked inheritance patterns have been suggested, and one large pedigree has demonstrated autosomal dominant inheritance. The variability and age limitations in clinical phenotypic diagnosis present several problems to genetic analysis, because information on members of the youngest and older generations may be lost to the analysis. The purpose of the present study was to elucidate the genetic basis of JP by formal pedigree analysis and comparison of competing genetic models. Twenty‐eight families were included, with general and specific autosomal models, and an X‐linked model being compared. The autosomal recessive model provided the most parsimonious explanation of the data, and its likelihood was not significantly different from the more general model. Likelihoods for the sporadic (nongenetic) and X‐linked models were considerably lower than the autosomal models. While comparison of genetic models suggests recessive inheritance of JP, the serious complications to pedigree analysis posed by limitations warns against acceptance of this conclusion, without more exhaustive evaluation of: (1) a more extensive collection of family data, (2) more complete investigation of the effects of age limitations on comparisons among competing models, and (3) elucidation of the importance of diagnosis and phenotype assignment of adults through past dental records.

Risk Factors of Periodontal Disease: Review of the Literature

“…This variability in presentation of significant signs of disease makes diagnosis difficult, not only in declaring if a patient suffers from the disease but also in detecting patients who do not suffer from the disease and differentiating between adult and aggressive forms of periodontitis. The problems associated with the clinical differentiation of periodontal disease are not uncommon in medical genetics, since similar problems arise in the study of other delayed-onset hereditary traits [133]. …”

Genetic Influences in Caries and Periodontal Diseases

“…When the original pedigrees were analyzed redressing for ascertainment bias, they were found to be supportive of autosomal inheritance of EOP (Hart et al, 1992). Both autosomal-recessive inheritance (Saxen and Nevanlinna, 1984;Beaty et al, 1987;Boughman et al, 1988Boughman et al, , 1992 and autosomal-dominant inheritance (Boughman et al, 1986;Marazitta et al, 1991) of early-onset periodontitis are supported by existing data. In the largest study to date (100 families), Marazitta and colleagues (1994) found the strongest evidence for an autosomal-dominant susceptibility gene, with 70% penetrance.…”

Genes and Gene Polymorphisms Associated with Periodontal Disease

“…This variability in presentation of significant signs of disease makes diagnosis difficult, not only in declaring if a patient suffers from the disease but also in detecting patients who do not suffer from the disease, and differentiating between adult and aggressive forms of periodontitis. The problems associated with the clinical differentiation of periodontal disease are not uncommon in medical genetics, since similar problems arise in the study of other delayed-onset hereditary traits (Boughman et al, 1988;Potter, 1989).…”

“…Huntington's chorea is another example of a hereditary disease where the diagnosis is possible only relatively late in life (OMIM 143100). The problems of genetic model testing in aggressive periodontitis (AgP) have been highlighted by Boughman et al (1988), who noted that AgP has a variable age of onset and is often not recognized until after puberty, that the upper age limit of expression of the disease is curtailed (artificially by a diagnostic definition that loss of attachment in patients older than 35 years is attributable to chronic periodontitis), and that difficulties exist in acquiring periodontal disease histories in edentulous family members.…”