Family History: Unraveling the Genetic Impact on Myopia and Supernumerary Teeth

Genetics has played a significant role in my life since birth. I am an identical twin, a living example of the fascinating ways genetics can affect an individual. The expression of genes creates an imperfect science. While some gene expression results in normal human health characteristics, other times, it causes health issues and problems. Using the family genogram in Appendix A, I will examine two genetically-linked disorders, myopia and supernumerary teeth, their influence on my own familial and personal health, and what these disorders could mean for my children and subsequent generations.

Myopia

Myopia is an ocular condition where the eye grows too long from front to back, creating a spherical equivalent refraction where the lens of the eye focuses light in front of the retina, causing relative blindness. (National Eye Institute, 2017). Myopia is caused by mutations in the visually-evoked signaling cascade, causing erroneous ocular development (Flitcroft et al., 2018). Myopia is diagnosed through optic nerve and retina imaging and can be corrected using corrective lenses. Refractive surgeries such as keratomilasis (reshaping of the cornea) or keratectomy (surgical removal of part of the cornea) can better focus light and information on the retina, correcting the refraction (National Eye Institute, 2017). Once myopia is diagnosed, subsequent ocular examinations are performed to evaluate spherical equivalent refraction.

Genetic Risk Factors for Myopia

According to Verhoeven et al. (2013), the exact pathogenesis of myopia is mainly unknown, but it has been correlated to at-risk genes associated with the visually-evoked signaling cascade during embryonic development and autosomal single nucleotide polymorphisms or mutations. Flitcroft et al. (2018) advise that a single polymorphism or mutation can affect a gene’s expression leading to variations in refractive error and producing tissue issues in the eyes and other organs. Studies have identified many genes that are at risk for potential refraction error (Verhoeven et al., 2013), which include GJD2, RASGRF, GRIA4, A2BP1, and retinoic acid (RORB, CYP26A). These genes regulate neurotransmission in the retina during ocular tissue growth and development (Jiali & Qingjiong, 2017). The GJD2 gene forms gap junctions between retinal neuronal cells allowing for active extracellular matrix remodeling, which, if altered, can result in the relative lengthening of the eye. RASGRF is a nuclear exchange factor that allows for the exchange of GDP/GTP in photoreceptor responses within synapses. GRIA4 occurs in many retinal cells, mediating fast-excitatory neurotransmission and aiding in retinal light-signaling. A2BP1 is an RNA-splicing regulator modulating cell membrane excitability. Retinoic acid (RORB, CYP26A) contributes to the remodeling and cell differentiation of the extracellular matrix, leading to scleral matrix remodeling and malformation. Verhoeven et al. (2013) stress that many other regulatory genes have yet to be researched for association with myopia. While those genes remain unknown, the identification of the above-mentioned genes holds promise for further research.

Personal and Future Generation Risk for Myopia

I have a family history of myopia on both sides of my family. One of my paternal uncles and three of my maternal uncles were diagnosed with myopia in childhood. They were treated with corrective lenses and did not have any further ocular complications. My twin sister and I were born prematurely and were diagnosed with myopia prior to discharge from the neonatal intensive care unit following our birth. According to Holmstrom and Larsson (2005), prematurity increases the prevalence of myopia. We were both monitored through childhood via ocular examination until our Vision was determined stable.

Myopia risk is increased in children whose parents have myopia (Xiaoya et al., 2015). The odds ratio of a child having myopia is 1.53 if one parent has myopia and 2.13 if both parents are affected. This is important information for those affected by myopia to keep in mind for their own children. Currently, the pathogenesis of myopia is still being studied, with the hope that the studies will illuminate possible interventions to prevent myopia or avert the severest of related disorders (Xiaoya et al., 2015). Until such interventions are established, careful examination at regular intervals of the refractive errors guides treatment. According to Holmstrom and Larsson (2005), retinoscopies performed at six months, 2.5 years, and then ten years of age can be used to trend refraction error progression. The retinoscopic measurements of the refraction error at 2.5 years of age can help predict the measurements at ten years of age. This tool can help parents of myopic children anticipate the potential progression of the child’s disease.

Supernumerary Teeth

The condition of supernumerary teeth is an anomaly characterized by an excessive number of teeth in relation to the normal dental formula (Subasioglu et al., 2015). Supernumerary teeth can either occur as an isolated condition or accompany other dental or connective tissue disorders. The cause of supernumerary teeth can be environmental or a congenital genetic disorder due to the loss of regulation in tooth morphogenesis. The presence of extra teeth can be asymptomatic. However, it usually presents with clinical complications, such as eruption failure or the rotation of permanent teeth (Subasioglu et al., 2015). Supernumerary teeth are diagnosed through a general oral exam and imaging to confirm extra unruptured teeth. The extra unruptured teeth are removed surgically to minimize the risk of further complications. Further imaging is recommended to evaluate for other connective tissue and dental anomalies, such as impaction, overcrowding, rotated permanent teeth next to the extra teeth, and formation of follicular cysts (Xi et al., 2017).

Genetic Risk Factors for Supernumerary Teeth

Supernumerary teeth disorders arise from a decline in the expression of the adenomatous polyposis coli (APC) gene during the embryonic phase of development (Fang et al., 2018). Such a decline is most often caused by congenital genetic disorders, as well as environmental fetal infection or trauma (Fang et al., 2018). The APC gene is responsible for the regulation of cell expression, proliferation, and differentiation (National Eye Institute, 2017). A decline in APC expression causes an upregulation of the bone morphogenesis protein, fibroblast growth factor, and tumor necrosis factor (Xi et al., 2017). This upregulation affects the signal pathways of the epithelium and ectomesenchyme of the maxilla and mandible, causing dental lamina hyperactivity. Dental lamina hyperactivity leads to the formation of supernumerary teeth.

Personal and Future Generation Risk for Supernumerary Teeth - Family History

My maternal grandmother was the first on my mother’s side to be diagnosed with supernumerary teeth. She was in her early twenties and had an extra set of incisors growing behind her permanent teeth. At the time, her overall dentition was poor, so the treatment was to remove all her adult teeth, along with the supernumerary teeth. She has worn dentures since that surgery. None of her children had supernumerary teeth or other dental anomalies. My paternal uncle was the first known person on my father’s side diagnosed with supernumerary teeth. He was a teenager at the time of his diagnosis, and the teeth were removed with no other issues. My twin sister and I were diagnosed with supernumerary teeth, with no other dental anomalies, at age 7. We each had an extra set of incisors which were subsequently surgically removed. Our permanent incisors would not descend, and braces were eventually placed, and the adult teeth pulled down mechanically over the course of 6 years.

According to Fang et al., the genetic predisposition of supernumerary teeth can possibly be linked to a disorder of a dominant, autosomal gene. However, the exact link is unknown. Researchers hope to find inheritance criteria to possibly help guide prenatal diagnosis of supernumerary teeth. In examining my own familial history of supernumerary teeth, a prenatal diagnosis is potentially exciting. Supernumerary teeth can cause other dental issues, some more severe than others, such as the formation of follicular cysts. The diagnoses of certain connective tissue disorders can follow supernumerary teeth diagnosis. If a prenatal diagnosis of supernumerary teeth becomes a possibility in the future, it would greatly benefit those with the disorder. A prenatal diagnosis of supernumerary teeth and an established inheritance pattern would mitigate potential complications from the disorder and guide clinicians to appropriate interventions.

Conclusion

Both myopia and supernumerary teeth are genetically-linked disorders that can have meaningful health implications and sequelae. Unfortunately, it remains unknown if there are ways to avert the genetic expression of these disorders. My twin sister and I have unusual health histories because we inherited genetic disorders from both sides of the family, each disorder expressed identically between the two of us. Fortunately for previous generations of our family, neither myopia nor supernumerary teeth caused or were found to correlate to any other disorders of the eyes or teeth. The future of genetically-linked disease diagnosis, intervention, and management is improving with every new study conducted.

References

1. Fang, Y., Wenping, C., Beizhan, J., Laijun, X., Shangfeng, L., & Shouliang, Z. (2018). Mutation of the adenomatous polyposis coli (APC) gene results in the formation of supernumerary teeth. Journal of Cellular and Molecular Medicine, 22(1), 152-162. doi: 10.1111/jcmm.13303.
2. Flitcroft, D. I, Loughman, J., Wildsoet, C., F., William, C., & Guggenheim, J. A. (2018). Novel myopia genes and pathways identified from syndromic forms of myopia. Investigative Ophthalmology and Visual Science, 59(1), 338-348. doi: 10.1167/iovs.17-22173.
3. Holmstrom, G. E. & Larsson, E. K. (2005). Development of spherical equivalent refraction in prematurely born children during the first ten years of life: A population-based study. Archives of Ophthalmology, 123(10), 1404–1411. doi:10.1001/archopht.123.10.1404.
4. Jiali, L., & Qingjiong, Z. (2017). Insight into the molecular genetics of myopia. Molecular Vision, pp. 23, 1048–1080. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757860/.
5. National Eye Institute. (2017). Facts about Myopia. Eye Health Information: Refractive Errors. Retrieved from https://nei.nih.gov/health/errors/myopia.
6. Subasioglu, A., Savas, S., Kucukyilmaz, E., Kesim, S., Tagci, A., & Dundar, M. (2015). Genetic background of supernumerary teeth. European Journal of Dental Education, 9(1), 153-158. doi 10.4103/1307-7456.149670.
7. Verhoeven, V. J., Hysi, P. G., Wojciechowski, R., Fan, Q., Guggenheim, J. A, Hohn, R.,...Kemp, J. P. (2013). Genome-wide meta-analyses of multi-ancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics, 45(3), 314–318. doi: 10.1038/ng.2554.
8. Xi, L., Fang, Y., Junjun, L., Wenping, C., Yumei, Z., Shouliang, Z., & Shangfeng, L. (2017). The epidemiology of supernumerary teeth and the associated molecular mechanism. Organogenesis, 13(3), 71-82. Doi 10.1080/15476278.2017.1332554.
9. Xiaoya Z., Xinhua, Q., & Xingtao, Z. (2015). Association between parental myopia and the risk of myopia in a child. Experimental and Therapeutic Medicine, 9(6), 2420–2428. doi 10.3892/etm.2015.2415.

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