Literature Review of the Aetiology of MIH (Dissertation Sample)

Literature Review of the Aetiology of MIH First and Last Name Department and Academic Institution Course Name and Number Instructor Due Date Literature Review of the Aetiology of MIH Introduction Molar-incisor hypomineralization (MIH) is described as a common but perplexing and multifactorial developmental dental condition that is characterised by enamel defects that affects one or more first permanent molars and accompanying incisors (Elhennawy et al., 2016). The condition is caused by the reduction of the mineral and inorganic composition of the enamel which results in discolouration and fracturing of the teeth and increased sensitivity to temperature (Elhennawy et al., 2016). Until now, the main causes or aetiology of MIH has remained relatively unclear, although recent studies have theorized and suggested that it develops from a complex interplay between generic predispositions of individuals and environmental (Exposure) variables, particularly those related to early childhood exposures. Historically, MIH was thought to primarily be influenced or caused by genetic predisposition of individuals as well as medical complications during different stages of pregnancy (Jeremias et al., 2013), however, recent studies have found that environmental variables also contribute significantly to the occurrence of the condition (Silva et al., 2019). Among these environmental variables, the influence of environmental toxins, dietary habits, systemic diseases, and prenatal factors has been extensively studied and debated within the scientific community. These environmental factors influence tooth development during various stages, including prenatal (before birth and during fetal development), perinatal (immediately before and after birth, typically from the 20th to the 28th week of gestation to 1 to 4 weeks after birth), and postnatal (following birth, encompassing infancy and early childhood) periods of tooth development. Ultimately, these studies have suggested that further research involving more accurate, larger and more diverse populations is necessary for a comprehensive understanding of the multifactorial nature of MIH and the significance of both the genetic and environmental variables in its aetiology. According to Smith et al., 2020, while a majority of MIH research work has in the past focused on the genetic predisposition of individuals as their area of concern in the occurrence of MIH, emerging evidence suggests that environmental/exposure variables may play a more crucial role in the susceptibility to the condition. Therefore, although the understanding of candidate gene studies and genome-wide association studies have been crucial in identifying the genetic variants associated with MIH and shedding light on the complex interplay between genetic variables and enamel development (da Silva et al., 2021), it is as well crucial to understand and incorporate the significant impact of environmental(exposure) variables to better elucidate underlying mechanisms, identify at-risk populations, and inform personalized prevention and treatment strategies. This literature review aims to comprehensively examine the current body of evidence regarding the impact of environmental (exposure) variables on the etiology of MIH, providing updated evidence, critical analysis and insights to enhance our understanding of this intricate condition. We will investigate the influence of prenatal, perinatal, and postnatal environmental/exposure variables on MIH susceptibility, considering recent research findings and methodological considerations. By synthesizing evidence from environmental perspectives, this review aims to provide insights into the multifactorial aetiology of MIH and guide future research directions in this field. Genetic Variables and the Development of MIH Given the complex and multifactorial nature of the aetiology of MIH, it is obvious that the genetics of an individual plays a crucial role in whether or not they get affected by the condition. Recent studies estimate that close to 20% of MIH in an individual can be attributed to the genetic composition of the said individual (Vieira, 2019). 1 Candidate Gene Studies Other studies have gone as far as purporting that there is a gene in chromosome twenty-two in an area referred to as the "SCUBEI" which is associated with the Metalloproteinase 20 (MMP-20), the AMBN, the ENAM, and the Amelogenin (AMELX) genes that are responsible for the pathogenesis of MIH (Jeremias et al., 2013). These genes are also the ones responsible for the formation of the enamel. 2 Genome-Wide Association Studies (GWAS) GWAS have identified novel genetic loci associated with MIH susceptibility, providing insights into the polygenic nature of this condition. For example, a recent GWAS conducted by Kühnisch et al. (2014) identified several genetic variants in genes involved in calcium ion binding and enamel mineralization pathways that were significantly associated with MIH risk. These findings underscore the complex interplay of genetic variables in the aetiology of MIH. 3 Epigenetic Mechanisms In addition to genetic variations, epigenetic modifications, such as DNA methylation and histone acetylation, may contribute to the development of MIH. Epigenetic alterations can influence gene expression patterns and protein function, potentially impacting enamel formation and mineralization processes. Further research is needed to elucidate the role of epigenetic mechanisms in MIH pathogenesis (da Silva et al., 2021). Criticism of Genetic Studies on the aetiology of MIH While genetic studies have provided valuable insights into the aetiology of MIH, several criticisms and limitations warrant consideration. Small Sample Sizes Many genetic studies on MIH have been limited by small sample sizes, reducing statistical power and potentially leading to false-positive findings. Larger, well-powered studies are needed to confirm the associations observed and identify novel genetic risk factors for MIH (Ghanim et al., 2020). Population Heterogeneity MIH is a heterogeneous condition with variable clinical presentations and severity. Genetic studies often lack adequate representation of diverse populations, limiting the generalizability of findings and potentially overlooking population-specific genetic risk factors (da Silva et al., 2021). Gene-Environment Interactions Genetic predisposition to MIH may interact with environmental variables, such as fluoride exposure and nutritional status, in complex ways. Studies often fail to account for these gene-environment interactions, leading to an incomplete understanding of the underlying mechanisms driving MIH development (Ghanim et al., 2020). Genetic studies have shed light on the complex aetiology of MIH, implicating multiple genetic variables in disease susceptibility. While promising, these findings must be interpreted with caution and validated in larger, more diverse cohorts. Addressing the limitations of existing genetic studies, including small sample sizes, population heterogeneity, and gene-environment interactions, is essential for advancing our understanding of MIH pathogenesis and informing targeted prevention and treatment strategies. Environmental (Exposure) Variables and the Aetiology of MIH Environmental variables are another source of complication that results in the formation of molar-incisor hypomineralization. Studies have provided evidence that suggests that environmental exposures during critical periods of tooth development may also play a significant role in the aetiology of MIH. These variables can be categorised into prenatal, perinatal, and postnatal environmental exposures to MIH. In this section, we examine the influence of these environmental variables on MIH and critically evaluate the strengths and limitations of existing studies. Pre-natal Variables Maternal Health Conditions Maternal health during pregnancy can impact fetal development, including tooth mineralization. Conditions such as gestational diabetes, pre-eclampsia, and maternal infections during pregnancy all play a significant role in influencing foetal development, including enamel formation. These prenatal variables result in the disruption of the intricate processes involved in the mineralisation of the enamel which in turn results in the development of MIH in the offspring. In a study conducted on Swedish Children by Jälevik et al. (2005) which examined the relationship between maternal illnesses during pregnancy and the occurrence and severity of MIH, it was discovered that the first trimester in a pregnancy which is accompanied by high fever was strongly associated with an increased risk of the development of MIH in the children. This demonstrated that maternal health conditions or illness during foetal development had significant influences on the development of MIH. Similarly, a study by Silva et al., (2019) emphasised this fact by pointing out that lack of or deficiency of maternal Vitamin D during pregnancy was linked to inadequate formation of the enamel and by extension the occurrence of MIH in the offspring. Maternal Nutrition In the foetal development process, proper nutrition for the mother during pregnancy is essential. Nutrition is important in the prevalence and/or severity of the MIH condition as it is crucial in dental enamel formation. A study by Dantas-Neta et al. (2020) emphasised this fact while investigating the association between maternal nutrition status and the prevalence of MIH in Brazilian Children. In the study, it was found that maternal anaemia during pregnancy was a significant contributor to the increase in the risk of the development of MIH in offspring. This underscores the value of proper maternal nutrition during pregnancy. Maternal Smoking and Substance Abuse Maternal smoking and substance abuse during pregnancy have been associated with an increased risk of MIH in offspring. A study by Alalu...