Tooth agenesis patterns and phenotype variation in a cohort of Belgian patients with hypodontia and oligodontia clustered in 79 families with their pedigrees.

BACKGROUND Even though tooth agenesis is the most common developmental anomaly of the human dentition, its genetic background and pathogenic mechanism(s) still remain poorly understood. Syndromic and isolated forms of hypodontia have been described and can occur sporadically or in families. OBJECTIVES We describe and analyse the hypo-/oligodontia phenotype variations in families. The index patient suffers from severe or mild hypodontia; case-parents/sib records are available. Furthermore, we aim to evaluate whether the different agenesis patterns in the pedigrees are predictive of mutations in specific genes based on reported genotype-phenotype associations. MATERIALS AND METHODS Dental records and pedigrees were collected from 79 families. In 67 families, the index patient presented with oligodontia while in 12 families with hypodontia. The phenotype data of 66 oligodontia index patients were analysed with the Tooth Agenesis Code software. RESULTS Nine families counted two members; one family counted three members affected with oligodontia. Twenty-four oligodontia families respectively had one (n = 17), two (n = 4), three (n = 2) or four (n = 1) additional family members presenting with hypodontia. Of the 77 oligodontia cases, two showed the same tooth agenesis pattern, while 75 patients showed unique tooth agenesis patterns. CONCLUSIONS Despite familial aggregation and expected Mendelian segregation, the number of missing teeth in the familial hypo-/oligodontia phenotypes and the tooth agenesis patterns are highly variable between the affected family members. Therefore, we hypothesize that tooth agenesis is not (always) a simple monogenic condition, but additional genetic or environmental factors can modify the expression of the phenotype.