Ankyloglossia

Introduction

Ankyloglossia is the clinical term for the short lingual frenulum, that restricts the range of motion of the tongue, with prevalence in the population ranging between 4.2% and 10.7%.  The lingual frenum connects the ventral side of the tongue to the floor of the mouth.  Occasionally the frenum can attach to the mandibular alveolar ridge.  The morphogenetic basis of ankyloglossia is unknown and there is conjecture to whether it can be described as pathogenic, as it is more likely just individual variation.  It has been shown however to be related to problems associated with breastfeeding and speech. The abnormality seems to be more prevalent in males, with a ratio of 1.5–2.6: 1.0. 1–3

The relationship between structure, function and what is considered the accepted ‘normal’ lingual frenum is still unclear, and the diagnosis of ankyloglossia has varying degrees of subjectivity. Some grading systems for ankyloglossia identify several features including the lingual frenum complex appearance, the range of motion of the tongue relative to maximum interincisal opening or the position of the most anterior attachment of the frenum on the underside of the tongue.  These diagnostic templates include all possible variants of the lingual frenum and can be confusing with the chance that any particular frenum being allocated a grade of ankyloglossia which may be considered "abnormal". Also, the use of these diagnostic templates, together with a lack of understanding of embryological development and the differentiated anatomical structure seems to have contributed to confusion regarding what is "normal” lingual frenum anatomy1,3,6,7

When the infant tongue is dissected and elevated, as depicted in fig 1 it is easy to visualise the midline fold forming the lingual frenulum. The height of the frenum attachment on the ventral surface of the tongue altered the appearance of the frenum when placed under tension.8

Histology of the lingual frenum

The histology of the lingual frenum should help to identify characteristics typical of  a restricted lingual frenal attachment as the example seen in fig 3.

A study by Martinelli and Marchesan in   described the histological characteristics of human lingual frenulum. The children in the study underwent lingual frenectomy and tissue sections were studied. The frenum in these examples show significant bundles of muscle fibers within the dissected frenum.  It is unclear how the precise this dissection was and if these histological photomicrographs are a true representation of a restricted frenum. The muscle fires were scattered on the fold mucosa and had an increased number of collagen type I fibers, compared to controls.

Fig. 3 Photomicrograph of ankyloglossia. Significant bundles of muscle fibers (arrows) were observed in the frenulum with ankyloglossia. Masson's trichrome stain.

Martinelli and Marchesan in 2010

Embryology and Morphogenesis of the floor of the mouth.

The  tongue is derived from the first 4 pharyngeal arches, although the contribution from arch 2 is minimal.  The development of the tongue takes place between the 4th and 10th week gestation (CITATION?). The anterior 2/3 or ‘oral portion’ of tongue develops from three swellings on the lingual side of the first pharyngeal arch. The posterior 1/3 of the tongue is derived from arch 3 while the epiglottis is derived from arch 4. The tongue is composed of ectoderm, endoderm, mesoderm and neural crest-derived mesenchyme. A complex interaction of CNCC (Cranial Neural Crest Cells) and the mesodermal mesenchyme takes place. Parada and Chai 2012 using lineage tracing in mouse models demonstrated that CNCC populate the tongue primordium before the invasion of myogenic progenitors, suggesting that CNCC are the cell type initiating and directing tongue development. The CNCC give rise to connective tissue and vasculature  within the tongue.

Tongue muscle cells originate from the occipital somite’s that migrate to the tongue primordium along the hypoglossal cord.  Therefore, it is likely that muscles in the frenum are also derived from the occipital somites.

Fig.3 legend missing

Fig. 4.Embryonic muscles and their progenitors in 11- and 13.5-day mouse embryos are visualized using a myoid-LacZ transgene. During the interval between these stages, most individual

head muscles, including the tongue muscles and facial muscles, become segregated and arrive at their definitive locations. This is evident especially in the muscles associated with branchial arches 1 and 2 (BA1, BA2). Micrographs provided by David Goldhamer; original data from Kucharczuk et al. (1999). 18

Although no precise embryologic cause of ankyloglossia has been identified, it may be a combination of dysfunctional apoptosis during development anterior-medially of the lingual prominence, over fusion of the lateral lingual prominences, or a lack of anterior tongue length development, which are all under epigenetic influence. The net result may be an exaggerated attachment of mucosa and/or fibromuscular configuration with restricted functional mobility and altered anatomy.  Genetic factors may also play a role in the morphogenesis of the lingual frenum.

Genetics of Ankyloglossia

There are several syndromes that feature ankyloglossia (Table 1). The three genes causing the syndromes are TBX22, RSPO2, FAMIIIA, and SPECC1L.  The gene most closely associated with ankyloglossia is TBX22 (T box containing transcription 22). This gene is  mutated in families with X-linked cleft palate and ankyloglossia (CPX). TBX22  is expressed in the palatal shelves as well as the lingual frenum (see fig.5) 10,11.  Cleft palate with ankyloglossia is inherited as a semi-dominant X-linked disorder.  

In non-syndromic ankyloglossia, the tongue phenotype is isolated. The candidate gene that has been studied in detail is TBX22. The premise is that a gene that causes a related syndrome may also contribute to phenotypes that are less severe than the syndromic version. Several groups have studied populations with isolated ankyloglossia. In one study, putative missense mutations in TBX22 were identified in patients with isolated ankyloglossia 13. In another study, mutations in the coding region of TBX22 were found in cases with ankyloglossia. 12  Pauws et al 2009, explored mutations outside of the TBX22 coding region which might contribute to the resultant phenotype, where a non-coding upstream exon and its upstream regulatory region was investigated14. No unique mutations were identified, but seven, rare, single nucleotide polymorphisms were noted. These variants segregate into four distinct haplotypes. Individually, two of the SNPs associate significantly with cleft palate, as does the haplotype containing the rare allele of both SNPs. The presence of ankyloglossia segregates with the rare SNPs. The overall risk of being born with a cleft appears to increase with this TBX22 haplotype. Ankyloglossia may be a microform of cleft palate only thus it is important to examine all family members where CP is present (CITE Kantaputra et al., 2011) 14

 Fig 5. The developing nose and palate are the major sites of TBX22 expression, although we see expression in the frenum. TBX22 is expressed in the developing nasal septum but not in the fused palatal shelves 11

Mouse models for CPX

This section was supposed to be added in the written because it was missing in the oral. Pauws et al., 2009. This paper is the best evidence that TBX22 is functionally required for palate fusion and lingual frenum formation.

Clinical treatment options

There are several categories to management of ankyloglossia which include monitoring and assessment of function, non-surgical therapies and finally surgical interventions. The position paper on the contribution of ankyloglossia to breast feeding or speech abnormalities (Canadian Agency for Drugs and Technologies in Health, 2016) says that there is no evidence that surgical intervention improves clinical function.

The role of untreated ankyloglossia on speech, malocclusion16, mandibular incisor irregularity, gingival recession, mandibular growth, and tongue mobility in older children has been considered but there is little supporting evidence.

Nevertheless, if a referral is made to a dentist or physician to perform a releasing procedure, there are several options available including frenotomy/frenectomy with or without myotomy or Z-plasty. In most cases frenotomy is sufficient. A common frenotomy technique involves cutting of the frenum down to the base of the muscle with scissors. Hemostasis is obtained with pressure and sutures.  

Conclusion

Diagnosis and management of ankyloglossia in the infant is still a source of confusion depending on what confirmation biases the clinician may hold. Surgically, frenotomy is a low-risk procedure that is likely to be beneficial to some infants and mothers, but the natural history of untreated ankyloglossia used as a comparison has not been studied.  There is a trend for a restricted frenal attachment and other muscular dysfunction to be blamed for many craniofacial anomalies such as dental malocclusions, craniofacial growth disorders, swallowing disorders, chewing disorders, airway patency and even pediatric sleep apnea17.  That’s not to say it might have some contribution, there is just no current sound evidence to support these theories, especially when we start to understand that the growth of the craniofacial complex is influenced by multiple intricacies at the most basic molecular level.  

The variability in treatment outcomes and presentation of ankyloglossia indicate that the complexity of infant feeding mechanisms and tongue development is not fully encapsulated in simplistic ankyloglossia etiology framework as suggested by many in the “tongue-tie” industry. Consistent terminology with emphasis on symptomatic ankyloglossia and a uniform grading system will help with a sound protocol to diagnose and treat appropriately.

Closer to home, a study based on population data from British Columbia, the incidence rate of interventive frenotomy increased by 89% from 2004 to 2013, rising from 2.8 to 5.3 per 1000 live births. This suggests an increased awareness and associated treatment, hopefully not unwarranted! 18

1. Walsh, J. & Tunkel, D. Diagnosis and Treatment of Ankyloglossia in Newborns and Infants: A Review. Jama Otolaryngology Head Neck Surg (2017). doi:10.1001/jamaoto.2017.0948

2. Charisi, C., Koutrouli, A., Moschou, A. & Arhakis, A. Aetiology, Diagnosis and Treatment of Ankyloglossia. Balkan J Dent Medicine 21, 141–145 (2017).

3. Ricke, L. A., Baker, N. J., Madlon-Kay, D. J. & DeFor, T. A. Newborn Tongue-tie: Prevalence and Effect on Breast-Feeding. J Am Board Fam Pract 18, 1–7 (2005).

4. Kapoor, V., Douglas, P. S., Hill, P. S., Walsh, L. J. & Tennant, M. Frenotomy for tongue‐tie in Australian children, 2006–2016: an increasing problem. Med J Australia 208, 88–89 (2018).

5. Kotlow, L. Ankyloglossia (tongue-tie): a diagnostic and treatment quandary. Quintessence Int Berlin Ger 1985 30, 259–62 (1999).

6. Yoon, A. et al. Toward a functional definition of ankyloglossia: validating current grading scales for lingual frenulum length and tongue mobility in 1052 subjects. Sleep Breath 21, 767–775 (2017).

7. Hong, P. et al. Defining ankyloglossia: A case series of anterior and posterior tongue ties. Int J Pediatr Otorhi 74, 1003–1006 (2010).

8. Mills, N., Keough, N., Geddes, D. T., Pransky, S. M. & Mirjalili, A. S. Defining the anatomy of the neonatal lingual frenulum. Clin Anat (2019). doi:10.1002/ca.23410

9. Parada, C. & Chai, Y. Current Topics in Developmental Biology. Part 1 Craniofacial Morphog Regen Cells Tissues Organs 115, 31–58 (2015). 

10. Braybrook, C. et al. The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia. Nat Genet 29, 179–183 (2001).

11. Braybrook, C. et al. Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients. Hum Mol Genet 11, 2793–2804 (2002).

12. Klockars, T., Kyttänen, S. & Ellonen, P. TBX22 and Tongue-Tie. Cleft Palate-craniofacial J 49, 378–379 (2011).

13. Kantaputra, P. N. et al. Cleft Lip with Cleft Palate, Ankyloglossia, and Hypodontia are Associated with TBX22 Mutations. J Dent Res 90, 450–455 (2010).

14. Pauws, E., Moore, G. & Stanier, P. A functional haplotype variant in the TBX22 promoter is associated with cleft palate and ankyloglossia. J Med Genet 46, 555 (2009).

15. Klockars, T. Familial ankyloglossia (tongue-tie). Int J Pediatr Otorhi 71, 1321–1324 (2007).

16. Yoon, A. et al. Ankyloglossia as a risk factor for maxillary hypoplasia and soft palate elongation: A functional – morphological study. Orthod Craniofac Res 20, 237–244 (2017).

17. D’Onofrio, L. Oral dysfunction as a cause of malocclusion. Orthod Craniofac Res 22, 43–48 (2019).

18. Noden, D. M. & Francis‐West, P. The differentiation and morphogenesis of craniofacial muscles. Dev Dynam 235, 1194–1218 (2006).

19. Canadian Anklyoglossia Blueprint.  Frenectomy for the Correction of Ankyloglossia: A Review of Clinical Effectiveness and Guidelines 2015


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