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Review of Etiology of Posterior Open Bite: Is There a Possible Genetic Cause?

Authors Huang W, Shan B, Ang BS, Ko J, Bloomstein RD, Cangialosi TJ

Received 19 September 2019

Accepted for publication 22 April 2020

Published 25 June 2020 Volume 2020:12 Pages 233—240


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Christopher E. Okunseri

Wei Huang,1,* Bo Shan,2,* Brittany S Ang,1 Jennifer Ko,1 Richard D Bloomstein,1 Thomas J Cangialosi1

1Department of Orthodontics, Rutgers School of Dental Medicine, Newark, NJ 07103, USA; 2School of Public Health, Rutgers University, Newark, NJ, 07103, USA

*These authors contributed equally to this work

Correspondence: Wei Huang
Assistant Professor, Department of Orthodontics, Rutgers School of Dental Medicine, 90 Bergen Street, Orthodontics/D884/Wei Huang, Newark, NJ 07103, USA
Tel +1 973-972-7895
Fax +1 973-972-0526

Abstract: Posterior open bite (POB) is one of the most severe malocclusions that can impair patients’ masticatory functions, yet it is also a condition that is poorly understood and not well studied. Most reported cases are either sporadic or idiosyncratic with a diverse yet poorly understood etiology. Although primary failure of eruption (PFE), lateral tongue thrust, and certain medical syndromes or pathology of the temporomandibular joints have all been shown to cause POB, the complex interplay of environmental and genetic factors makes its etiopathogenesis a difficult subject to understand and investigate. Here, we provide a comprehensive review of the etiology of posterior open bite. Additionally, a genetic cause for POB is proposed through a report of an apparently non-syndromic familial case series with high POB penetrance across two generations. Further investigations of the gene(s) and mechanism(s) involved can not only provide a unique opportunity to better understand POB and the intricate muscular-occlusal relationship, but also offer powerful insight into the most effective approaches to clinical management of these (and potentially other) malocclusions.

Keywords: posterior open bite, etiology, genetic, malocclusion

Etiology of Posterior Open Bite

Posterior open bite (POB) is one of the most difficult to treat clinical entities that can severely impair a patient’s masticatory function. However, it is also a condition that is not well understood and has not been well studied. It is described as a lack of posterior occlusal contact and frequently is accompanied by facial asymmetry,13 failure of teeth to erupt,49 temporomandibular disorders,2,10-12 or medical syndromes.13,14 The prevalence of POB is unknown but low, and despite its severe functional consequences the etiology remains unclear. Most reported cases are sporadic, idiosyncratic, or caused by primary failure of eruption (PFE). Here, we provide a comprehensive overview of the etiology of POB.

Failure of Tooth Eruption

POB can be a consequence of eruption failure of teeth, including mechanical failure of eruption (MFE) and PFE.6 MFE is most often caused by ankylosis, where the cementum is fused to the alveolar bone resulting in a tooth eruption defect. It usually affects one tooth and may respond to surgical luxation and orthodontic forces.8 PFE, on the other hand, is incomplete eruption of non-ankylosed teeth due to a defective eruption mechanism.4 PFE typically affects multiple posterior teeth with all teeth distal to the most mesially affected tooth exhibiting similar infraocclusion.4 Bilateral manifestation of PFE appears to be less than two times more frequent than unilateral.15 These teeth will become ankylosed if there is an attempt to extrude them orthodontically.4 Therefore, treatment options for PFE often include extraction followed by prosthetic replacement or possible segmental osteotomy. Mutations in several genes, such as parathyroid hormone receptor 1 (PTH1R)15,16 and histone methyltransferase 2C (KMT2C), have been identified to be strongly associated with PFE.17 Thus, for suspected PFE cases, genetic screening is recommended to facilitate diagnosis and treatment decisions.

Tongue and Masseter

A lateral tongue-thrusting habit may be a direct environmental cause of POB. Its presence has been described in several case reports and postulated to be etiological to regional POB.1820 However, many of these cases also present with another POB contributor such as unilateral mandibular hyperplasia or Class III skeletal relationship with posterior crossbite. Therefore, it can be difficult to determine whether the POB is due to the tongue thrust or the tongue is just malpositioned as a secondary effect of existing POB due to the lack of contact with the posterior teeth, as frequently seen in edentulous patients. Controlled studies are still lacking to address this question. Nonetheless, the tongue-thrusting habit creates a mechanical interference in posterior tooth eruption.21 Therefore, control of the habit and myofunctional therapy are generally needed for successful treatment and retention for many POB cases.21

Interestingly, the masseter muscle with or without a tongue habit may play an important etiological role in certain rare POB conditions. Duchenne muscular dystrophy (DMD) is a progressive genetic neuromuscular disorder characterized by deterioration of muscle strength and increasingly difficult ambulation starting in early childhood.22,23 Patients with DMD show a high percentage of POB occurrence without vertical skeletal aberrations.22,24 Their decreased tonus of masseter and enlarged hypotonic tongue are likely the cause of the POB.23,24 In a case report of post-traumatic trigeminal neuropathy caused by an orbital stab wound, unilateral POB was observed to be correlated with the atrophy of the ipsilateral masseter muscle,25 indicating a possible role of masseter in POB etiology.


Many pathological changes of the temporomandibular joints (TMJ) can lead to POB as a result of displacement of the mandibular condyle. A sudden appearance of POB can be caused by joint effusion from mandibular trauma or an acute episode of rheumatoid arthritis,10 as well as hemarthrosis from anticoagulant therapy26 or hemophilia.27 Posterior disc displacement,28,29 posterior displacement of the posterior fragment after a TMJ disc fracture12 and increased posterior thickness of the retrodiscal tissue11 can all cause a mandibular closing disturbance just before complete mouth closure, hence the occurrence of POB.

Unilateral condylar hyperplasia is a condition characterized by excessive growth and enlargement of one mandibular condyle.30 When the vertical overgrowth of the affected side is met with incomplete compensatory downward growth of the maxilla, ipsilateral POB may occur.2

Certain TMJ-related therapies such as arthroscopic disc repositioning and placement of an anterior repositioning splint have been shown to have a common occurrence of POB.31,32 While surgical overcorrection of the displaced disc and misshapen disc is the possible reason for post-arthroscopy POB,31 recapture of the disc in the correct position at mouth closing is considered causal for POB in some splint cases.32

Mandibular Advancement Therapy

Patients who use functional mandibular advancement appliances to manage obstructive sleep apnea/hypopnea syndrome often present with a POB side effect.33 Although the occurrence ranges anywhere from 0% (6 months treatment) to 51% (11 years treatment), it appears that the longer the treatment, the higher the POB incidence among these patients.3439 As these appliances hold the mandible in a forward and vertically opened position to prevent the pharyngeal airway from collapsing,34 transient contracture of the inferior lateral pterygoid muscle, forward and downward positioning of lower arch and protrusion of mandibular incisors have been suggested to contribute to the occurrence of POB.3436,40

Syndromes and Class III

Patients with amelogenesis imperfecta (AI),41,42 achondroplasia,14 Apert Syndrome,13 and DMD22,23 have all been reported to have POB as part of their craniofacial manifestations. AI in particular shows a high percentage of POB occurrence.41,42 However, the mechanisms related to these conditions remain unknown.

Additionally, several case reports have documented concomitant POB in Class III malocclusions (skeletal and/or dental).1,3,18,20,43-46 The POB, however, occurs often in the presence of other factors such as tongue thrust habits,18,20 vertical underdevelopment of the dentoalveolar process,18 a narrow maxilla with mandibular asymmetry,1 a history of cleft palate,46 perioral muscle strain,43 and multiple missing teeth.44

Proposing a Genetic Cause of Posterior Open Bite

Despite all the reported cases of POB, the etiology seems diverse and not well understood. The interplay between genetics and environmental factors often complicates the study of its underlying causes. In addition, it is unclear how much of a role genetics actually plays. Can genetics be a more direct etiological factor for POB without causing any other major craniofacial defects as seen in many syndromic conditions? Although there is no report so far on any genetic cause of POB in the literature (except for those indirectly caused by PFE), the possibility exists.

A Family of POB Cases

In the orthodontic clinic at Rutgers School of Dental Medicine, there is an interesting pedigree of POB cases with high penetrance across two generations but no syndromic conditions are reported. All patients have given their written consent for the publication of their case details. Institutional IRB approval has been granted by Rutgers University. Patient MM1, MM2 and MM3 are three Caucasian siblings all affected by POB. Their age at initial records was 16 years 1 month, 20 years 9 months and 24 years 9 months, respectively. As shown in Figures 13, all siblings presented with straight to mildly concave profiles, with moderately to severely retruded upper and lower lips. Their facial proportions (thirds and fifths) were relatively well balanced, but their lip muscle tones were high both in appearance and upon clinical examination. Lateral tongue thrust was detected among all three patients with clear scalloped dental marks on both sides of the tongue. The size of the tongue appeared to be within normal limits. All siblings had a Class II molar and canine relationships with significantly retroclined upper and lower incisors, a constricted upper arch, deep overbite, and mild to severe crowding. Patient MM2 and MM3 both presented with a mild Class II skeletal relationship while patient MM1 had a very mild Class III skeletal pattern. Patient MM1 was hypodivergent, MM2 normodivergent, and MM3 hyperdivergent vertically. The patients denied having any medical conditions or syndromes. However, patient MM1 was reported to have had failure to thrive as a newborn.

Figure 1 Pre-treatment records of patient MM1: (A) extraoral and intraoral photos; (B) panoramic radiograph; (C) cephalometric radiograph; (D) cephalometric measurements.

Figure 2 Pre-treatment records of patient MM2: (A) extraoral and intraoral photos; (B) panoramic radiograph; (C) cephalometric radiograph; (D) cephalometric measurements.

Figure 3 Pre-treatment records of patient MM3: (A) extraoral and intraoral photos; (B) panoramic radiograph; (C) cephalometric radiograph; (D) cephalometric measurements.

Upon inquiry into the family history, the mother and aunt of the three siblings also had similar POB, although their dental records were not available. None of the family members on the father’s side demonstrated any POB. Patient MM2, MM3, the mother and aunt received orthodontic treatment years ago with successful closure of the POB, but relapse occurred in patient MM2 and the mother at the time MM2 presented for initial records which was the reason for MM2’s second orthodontic treatment request.

This interesting family tree (Figure 4) of POB shows high generation penetrance and strongly indicates that there is a dominant genetic etiopathogenic factor involved. Because patient MM2, MM3 and the mother have all received previous treatment with successful closure of their POB, PFE and ankylosis can be excluded as an etiologic factor. The striking similarity of retruded upper and lower lips, increased lip muscle tones, significantly retroclined upper and lower incisors and lateral tongue thrust among the three siblings leads to our hypothesis that a dramatically increased lip muscle tone might be the direct target effect of the suspected genetic causal element. Increased lower lip pressure/activity has been well known to cause upper incisors retroclination in Class II Division 2 patients.47,48 Therefore, taut lip muscles could well cause retroclination of both upper and lower incisors, which would in turn reduce the anterior-posterior length of both arches. Shortened arches could restrain the tongue to a more posterior and lateral position leading to increased lateral tongue pressure, lateral tongue thrust/posture and ultimately POB. Alternatively, the genetic factor could also lead to the POB through a different mechanism while the tongue thrust/posture could simply be a secondary effect. Further studies through genetic linkage analysis or whole genome sequencing may help identify the underlying genetic factor of this pedigree of POB, and lay the foundation for better understanding of the mechanisms.

Figure 4 Pedigree of the M family.


Genetic studies of the etiology of malocclusion have been mostly focused on syndromic conditions. Many single gene syndromic disorders present with craniofacial and oral manifestations, such as Apert’s syndrome, Treacher Collins syndrome and cleidocranial dysplasia, caused by mutations in fibroblast growth factor receptor 2 (FGFR2), treacle ribosome biogenesis factor 1 (TCOF1) and Runt-related transcription factor 2 (RUNX2), respectively.49,50 Frequently, malocclusions which occur in these disorders are part of and secondary to a complex pattern of multiple dentofacial defects. Although no syndrome has been reported for the POB subjects reported here, it is possible that a syndromic condition with high penetrance and very low expressivity might be involved.

Non-syndromic mandibular prognathism is one of the few malocclusions that appears to have a strong genetic component without any other medical and/or dental defects.51 Chromosomes 1, 4, 6, 14 and 19 have all been shown to harbor genes that confer susceptibility,5255 with Matrilin-1,56 ADAMTS1,57 COL2A158 and EPB4159 known to be strongly associated with the condition. Many of the genetic components have been reported to be involved in craniofacial bone development as well as in the function of masticatory muscles, the condyles and growth hormones.55,56,60-62 This has shed light on the multi-mechanistic nature of many mandibular prognathism conditions, and has provided important indications for the multi-focus (rather than just the bone) approach to clinical treatment and retention.

The complex interplay of genetic and environmental factors makes the pathogenic mechanisms of malocclusion a difficult matter to dissect. Therefore, unusual hereditary non-syndromic malocclusions, such as this familial POB case series, offer a rare and unique opportunity for pinpointing important etiopathogenic factors, biochemical pathways, and mechanisms that would have been otherwise impossible to identify. Discovering the gene(s) involved and its function can thus not only advance our understanding of the cause and mechanisms of POB and help lay the foundation for better treatment strategies and outcomes. It could also provide powerful insight into the function of other gene products that interact with the identified gene(s). This, in turn, can help identify critical pathogenic pathways that are utilized by other non-genetic etiological factors for POB as well as many other malocclusions or oral conditions. A great example of how the study of a rare genetic disorder can have much broader applications is the early work on familial hypercholesterolemia, which led to the development of statins, the blood cholesterol-lowering drugs that are now among the most widely prescribed drugs in medicine.6365 With today’s vast information on human genome sequences, large databases and advanced genetic and molecular tools, the knowledge gleaned from a seemingly isolated familial POB series may impact the understanding of physiology and pathogenesis in ways which were unfathomable previously.


POB is one of the most challenging clinical entities that can severely impair a patient’s masticatory functions. The etiology of POB appears diverse and poorly understood with mostly case reports. Several conditions including PFE, ankylosis, tongue habits or masseter dystrophy, TMJ-related pathology and treatment, mandibular advancement therapy, as well as certain syndromes such as AI can all contribute to the occurrence of POB. Additionally, we report a non-syndromic familial case series with high POB penetrance across two generations and propose a possible genetic cause or predisposition for POB.


Wei Huang and Bo Shan are co-first authors for this study. The authors report no conflicts of interest in this work.


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