Craniofacial and dental development in Costello syndrome.

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n = 41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development.

Hypoplasia-associated severe early childhood caries--a proposed definition.

We propose a new classification of severe early childhood caries (S-ECC): hypoplasia-associated severe early childhood caries (HAS-ECC). This form of caries affects mostly young children living at or below poverty, characterized by structurally damaged primary teeth that are particularly vulnerable to dental caries. These predisposing developmental dental defects are mainly permutations of enamel hypoplasia (EHP). Anthropologists and dental researchers consider EHP an indicator for infant and maternal stresses including malnutrition, a variety of illnesses, and adverse birthing conditions. Differentiation of HAS-ECC from other forms of early childhood caries is warranted because of its distinct etiology, clinical presentation, and eventual management. Defining HAS-ECC has important clinical implications: Therapies that control or prevent other types of caries are likely to be less effective with HAS-ECC because the structural integrity of the teeth is compromised prior to their emergence into the oral cavity. By the time these children present to the dentist, the treatment options often become limited to surgical management under general anesthesia. To prevent HAS-ECC, dentists must partner with other health providers to develop interventions that begin with pregnant mothers, with the aim of eliminating or ameliorating the covariates accompanying poverty, including better pre- and post-natal care and nutrition.

Cytomegalovirus induces stage-dependent enamel defects and misexpression of amelogenin, enamelin and dentin sialophosphoprotein in developing mouse molars.

Of the approximately 8,400 children born each year in the US with cytomegalovirus (CMV)-induced birth defects, more than one third exhibit hypoplasia and hypocalcification of tooth enamel. Our prior studies indicated that CMV severely delayed, but did not completely interrupt, early mouse mandibular first molar morphogenesis in vitro. The aim of the present study was to examine the effects of CMV infection on progressive tooth differentiation and amelogenesis. Since initial CMV infection in human fetuses can occur at different developmental times, we varied the stage of initial viral infection (that is, Cap stage, Early Bell stage and Bell stage), as well as the duration of infection. CMV infection of embryonic mouse mandibular first molars in vitro induces tooth dysmorphogenesis and enamel defects in a developmental stage- and duration-dependent manner. Cap stage- and Early Bell stage-infected molars exhibit enamel agenesis and Bell stage-infected molars exhibit enamel hypoplasia. This viral-induced pathology is coincident with stage-dependent changes in Amelx, Enam and Dspp gene expression, distribution of amelogenin, enamelin and DSP proteins, cell proliferation localization and dedifferentiation of secretory ameloblasts. Importantly, our data indicate that specific levels of Amelx and Dspp gene expression define whether mouse CMV induces enamel agenesis or hypoplasia.

[Morphological changes in the primordia of the deciduous teeth during an exacerbated course of the antenatal period]. / Morfologicheskie izmeneniia zachatkov vremennykh zubov pri otiagoshchennom techenii antenatal'nogo perioda.

Histologic examination of 380 rudimentary deciduous teeth of 91 stillborn babies or corpses of newborns dead within 16 days after birth and comparison of the results with clinical data brought the authors to a conclusion that the diagnosis of enamel hypoplasia is erroneous because all dental tissues are involved during this condition. Pathohistologic changes in the enamel, dentin, and tissues adjacent to dental rudiment are described in detail, all these tissues developing under unfavorable conditions of antenatal odontogenesis.