Overview

Tongue-Tie (ankyloglossia) is a congenital condition present at birth characterised by the presence of a thin band of tissue (lingual frenulum) connecting the tongue to the floor of the mouth. It affects approximately 4% of the newborn population, resulting in a restriction in tongue mobility in babies.¹ This causes challenges in breastfeeding and difficulties in speech articulation in infants and children.² In order to effectively diagnose and manage this condition, it is essential to understand the underlying causes. This article will aim to explore the genetic predispositions and developmental factors that lead to the development of Tongue-Tie.

Genetic links to Tongue-Tie

Research has documented that there is a significant hereditary component in the development of Tongue-Tie. Studies have indicated that there is a familial link in individuals who develop Tongue-Tie and a high prevalence of the condition among first degree relatives who have the condition such as parents, siblings or children..³ A study published in Archives of Plastic Surgery suggests the presence of a gene in the X chromosome which may be responsible for the inheritance pattern of the condition.⁴

Other studies have indicated an autosomal dominant pattern of inheritance, with the gene being expressed in a variable manner.⁵ This means that, although some individuals with a genetic predisposition may exhibit the pronounced form of the condition, others will have a more subtle presentation or even be asymptomatic carriers. Despite the observation of hereditary links, the exact genetic causes are still unknown.

One mechanism has been identified in the WNT signalling pathway; a complex system of communication within cells that control growth, division and movement of cells. This pathway is important in the development of embryos and tissue maintenance in adults. A study published in the Journal of Biological Chemistry showed that this pathway is crucial in the development of muscle cells in the tongue, indicating the critical role it plays in tongue formation.⁷

Another set of genes which may be implicated in this condition are the HOX genes. These play a role in the development of the face and cranium and may influence the formation of the tongue. A study published in Development found that mutations in these genes have been associated with various structural abnormalities of craniofacial anatomy.⁸ However more research is needed in order to link the HOX gene directly to the development of Tongue-Tie. In fact, the lack of large-scale genomic studies has made it difficult to identify exact genetic links to the development of Tongue-Tie.

While genetic transmission is apparent, it is multifactorial. Interactions between multiple genes as well as epigenetics influence the likelihood of a child inheriting the condition.⁶ And so, while genetic inheritance is evident, the mechanism by which the condition is passed on is still being researched as many factors seem to influence the severity and manifestation of the condition.

Embryological development of Tongue-Tie

In order to discern how the condition manifests, it is important to understand the formation of the tongue. The structure begins to form around the fourth week of embryonic growth due to the merging of various structures in the growing fetus. The tongue develops in sections, with the anterior two-thirds developing from the first pharyngeal arch, and the posterior third arising from the third and fourth pharyngeal arches. Around the eighth week, these components join together with the frenulum in order to guide normal tongue mobility and attach the tongue to the floor of the mouth.⁹ When the frenulum fails to recede, restriction in tongue movement occurs and tongue-tie manifests.

During the development of the fetus, programmed cell death (apoptosis) eliminates unnecessary tongue and frenulum tissue, thereby creating an anatomically correct tongue. If this process does not occur correctly, the frenulum persists causing a restriction in tongue mobility.¹⁰ Studies have shown that individuals with a deficiency in the Sox2 gene, a gene responsible for preventing abnormal oral adhesions, are more susceptible to improper tongue adhesion to the floor of the mouth, which increases the likelihood of tongue-tie.¹¹

Environmental influences on Tongue-Tie development

While genetic factors are believed to play a role, environmental exposures during pregnancy may also contribute to the manifestation of the condition. Certain deficiencies in maternal nutrition determine the occurrence of various congenital conditions. The lack of folic acid, vitamin A and other essential nutrients are well-established causes of improper craniofacial development, including the presence of a pronounced lingual frenulum.¹² Tongue and oral cavity formation is known to be influenced by the presence of sufficient quantity of folic acid in maternal diet in early pregnancy, the lack of which has been associated with not only tongue-tie, but also other orofacial anomalies such as cleft palate.¹³

Maternal exposure to harmful substances and certain medications can affect the development of normal tongue anatomy. In particular, research has shown that prenatal exposure to alcohol and glucocorticoids can interfere with TBX22 expression (a gene responsible for regulating craniofacial development), therefore increasing the likelihood of cleft palate and tongue-tie.¹⁴ Furthermore, maternal exposure to tobacco smoke has been associated with an increased risk of craniofacial abnormalities due to its effect on foetal oxygen levels.¹⁵

Another environmental factor linked to the development of tongue-tie is the presence of gestational diabetes. Studies have demonstrated that maternal diabetes affects insulin and growth factors in the developing foetus, which cause abnormalities in oral structures, including the tongue and frenulum.¹⁶ Also, maternal exposure to endocrine-disruptors such as bisphenol A (BPA) and phthalates have been shown to interfere with developmental signalling pathways, increasing the risk of conditions such as tongue-tie.¹⁷

Conditions associated with Tongue-Tie

Tongue-tie is often associated with other craniofacial and developmental conditions such as cleft palate, a congenital anomaly that manifests as an incomplete roof of the mouth. Both conditions are connected to TBX22 gene mutations, which control the development of the palate and other oral structures.¹⁸ Indeed, some cases of tongue-tie occur along side cleft palate syndromes, where individuals present both an incomplete palate and a short frenulum.¹⁹

Other genetic syndromes have been associated with tongue-tie, such as Beckwith-Wiedemann syndrome (BWS) and Pierre Robin sequence (PRS). BWS is a condition of overgrowth that often leads to macroglossia (abnormally large tongue) as well as, more rarely, a restriction in tongue movement due to a tight frenulum.²⁰ In PRS, characterised by an underdeveloped lower jaw, cleft palate and airways obstruction, there is also the presence of tongue-tie and functional difficulties in certain individuals.²¹

However, functional abnormalities due to tongue-tie are not only responsible for speech challenges and difficulties in feeding in infants, but research has also indicated that tongue-tie can affect oral health. This is due to the increased risk of dental misalignment due to alterations in tongue mobility.²² Additionally, tongue-tie can also exacerbate sleep-disorders such as obstructive sleep apnoea by affecting proper tongue alignment and therefore air flow during sleep.²³

Summary

Tongue-Tie (ankyloglossia) is a congenital condition affecting around 4% of newborns. It causes a restriction in tongue mobility, and issues with breastfeeding and speech. Genetic factors may play a role in the development of the disease as a familial inheritance pattern has been observed. There is some evidence that genes such as TBX22, WNT and HOX are involved in the development of the tongue during foetal growth. However, it is when this process fails, and a pronounced frenulum persists that the condition manifests itself. Various environmental factors, such as maternal dietary deficiencies, exposure to chemicals and gestational diabetes also increase the risk. Tongue-tie is also linked to other congenital conditions such as cleft palate and may contribute to dental misalignment and breathing disorders. While research is still ongoing as to the exact causes of tongue-tie, it is evident that there are genetic as well as environmental factors that contribute to the manifestation of the condition.