Molecular-based phenotype variations in amelogenesis imperfecta

Amelogenesis imperfecta (AI) is one of the typical dental genetic diseases in human. It can occur isolatedly or as part of a syndrome. Previous reports have mainly clarified the types and mechanisms of nonsyndromic AI. This review aimed to compare the phenotypic differences among the hereditary enamel defects with or without syndromes and their underlying pathogenic genes. We searched the articles in PubMed with different strategies or keywords including but not limited to amelogenesis imperfecta, enamel defects, hypoplastic/hypomaturation/hypocalcified, syndrome, or specific syndrome name. The articles with detailed clinical information about the enamel and other phenotypes and clear genetic background were used for the analysis. We totally summarized and compared enamel phenotypes of 18 nonsyndromic AI with 17 causative genes and 19 syndromic AI with 26 causative genes. According to the clinical features, radiographic or ultrastructural changes in enamel, the enamel defects were basically divided into hypoplastic and hypomineralized (hypomaturated and hypocalcified) and presented a higher heterogeneity which were closely related to the involved pathogenic genes, types of mutation, hereditary pattern, X chromosome inactivation, incomplete penetrance, and other mechanisms.The gene-specific enamel phenotypes could be an important indicator for diagnosing nonsyndromic and syndromic AI.