Tuberous Sclerosis-associated enamel pitting and gingival fibromas: Familial vs. sporadic disease; genotype-phenotype correlations

Abstract

The purpose of this investigation was to study the incidence of enamel pitting and gingival fibromas in patients with tuberous sclerosis complex (TSC) and relate these findings to other physical findings of TSC, to sporadic and familial disease, and to specific TSC2 mutations. Methods: A total of 104 patients between 1 and 51 years of age were examined for enamel pits and gingival fibromas. All study subjects had a definitive diagnosis of TSC and were participants in a related study that provided results from MRI scans of the brain, echocardiography, renal ultrasound, neuropsychological assessments, and retinal examinations. Blood samples were obtained from each participant for DNA extraction and subsequent TSC mutational analysis. Results: Enamel pitting was seen in 29% of patients between 1 and 6 years of age, in 90% between 6 and 13 years of age, and in 100% of patients in the permanent 113 dentition. The majority of the pits were pinpoint sized and primarily affected the maxillary anterior arch. The maxillary central incisor was the most often affected permanent tooth and the maxillary canine was the most often affected primary tooth. Gingival fibromas were apparent in 47% of subjects in the mixed dentition and in 70% of subjects in the permanent dentition. Only one patient out of 31 in the primary dentition had a gingival fibroma. The majority of fibromas affected the interdental papilla of the maxillary anterior arch. There were few significant findings relating the degree and/or severity of enamel pitting and/or gingival fibromas to other physical findings of TSC. Enamel pitting in primary as well as permanent teeth were found to be strongly related to the presence of facial angiofibromas and a somewhat weaker association was seen with cardiac arrhythmias. Gingival fibromas were strongly related to the presence of facial angiofibromas and more weakly related to retinal lesions. There were no distinctions apparent between oral findings in sporadic and familial TSC nor were there any genotype-phenotype correlations between oral findings and TSC2 mutations. Conclusion: The combination of enamel pitting and gingival fibromas, as minor features of TSC, should raise the suspicion level regarding tuberous sclerosis as a diagnosis. Both are important minor features frequently seen which may help in establishing a definitive diagnosis. Scanning the dentition and gingiva is noninvasive, is inexpensive, and should be included in evaluating all patients suspect of a diagnosis of tuberous sclerosis.