Segmental Odontomaxillary Dysplasia: Systematic Review

Abstract

Purpose

This PRISMA-guided and PROSPERO-registered systematic review aimed to summarise the current knowledge on the characteristics (clinical, radiographic, and histopathological) and treatment options for segmental odontomaxillary dysplasia (SOD).

Methods

Descriptive studies, case series, and case reports were searched up to May 2024 in PubMed, Embase, Web of Science, SciELO, and the Cochrane Library databases. Statistical association analyses were performed on clinical variables, using chi-square tests.

Results

The 35 included studies detailed 60 SOD cases in patients with a mean age of 12 ± 9.6 years. 11. Males were more frequently affected than females (62% or 1.6:1 ratio). Most cases involved the right maxilla (55%) and presented facial asymmetry and/or unilateral swelling (78%). Three cases involved both maxillae and mandible; Skin alterations were reported in 50% of the cases. Intraoral alterations such as alveolar process enlargement and gingival hyperplasia were also frequently observed (84% and 58%, respectively). All patients presented tooth alterations and 1st and/or 2nd upper premolars were absent in 80% of the cases. Dense bone and altered trabecular patterns were frequently observed in radiographs. Histopathological exams commonly showed dense trabecular bone and hyperplasic gingival tissue. Only 33 cases reported the SOD treatment, which ranged from follow-up without intervention up to surgery and orthodontics. No significant associations were found between sex and facial asymmetry or continuous lesion growth (p > 0.05). Additionally, no associations were found between intraoral alterations or symptoms and continuous lesion growth (p > 0.05).

Conclusion

This review presents SOD epidemiological, clinical, radiographic and histopathological data. Evidence regarding treatment is scarce.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12105-024-01717-3.

Introduction

Segmental odontomaxillary dysplasia (SOD) unilaterally affects the maxillary bone and is frequently diagnosed during childhood and adolescence [1]. This rare and non-hereditary disorder was originally observed in two patients by Miles et al. in 1987 [2] and was recently included in the World Health Organisation’s (WHO) classification of head and neck tumours [1].

The painless enlargement of the maxillary bone and gingival tissue causes facial asymmetry, tooth absence, displacement, delayed tooth eruption, and root resorption [2–4]. Skin alterations such as hypertrichosis, hyper- or hypopigmentation, melanocytic nevi, and ectopic eyelashes may also be observed [3–8]. The acronym HATS (hemimaxillary enlargement, asymmetry, tooth and skin alterations) was introduced by some authors to describe the manifestations of SOD [8–10].

The current knowledge on the etiopathogenesis of SOD is limited and only a few cases have been reported. It is believed that a non-hereditary genetic alteration in the uterus causes a developmental defect in the first branchial arch [11]. Bacterial or viral infections have also been speculated to trigger SOD [4]. Genetic studies identified PIK3CA mutations in a suspected case of SOD, while mosaic ACTB mutations have been associated with the dermatological manifestations of this disorder [12, 13].

Since standard treatment protocols for SOD are not established, the diagnosis of this disorder requires a comprehensive evaluation of clinical, radiographic, and histopathological findings (1). Moreover, some cases require individualised and multidisciplinary approaches to treat SOD [4, 5, 14, 15]. This systematic literature review aimed to summarise the current knowledge on the characteristics (clinical, radiographic, and histopathological) and treatment options for SOD.

Materials and Methods

Study Design and Eligibility Criteria

This review was registered at the International Prospective Register of Systematic Reviews (PROSPERO - CRD42024539054) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) [16]. The PECO (Population, Exposure, Control, Outcome) approach was used to answer the research question “What are the clinical, radiographic, and histopathological characteristics of as well as the treatment options for SOD?”: (P) children and adults with SOD; (E) Not applicable; (C) Not applicable; (O) clinical, radiographic, and histopathological characteristics and treatment options.

Descriptive studies (prospective or retrospective), case series, or case reports of SOD with detailed information, without restrictions on language, diagnostic methods, or follow-up period were selected. Conversely, editorials, book chapters, narrative reviews, conference abstracts, and duplicate references were excluded.

Literature Search Strategy and Article Selection

Health sciences descriptors (DeCS), medical subject headings (MeSH), entree terms (Embase Subject Headings), and the boolean operators “AND” and “OR” were used to create search strategies on (Supplementary material 2) PubMed, Embase, Web of Science, SciELO, and the Cochrane Library databases up to May 2024 and updated in September 2024 (Supplementary material 1). The selection of articles for full-text reading was independently performed by two authors (ACAL and MQSS) and resolved by a third author (AF) in case of disagreement. The selected articles were imported to a reference manager (Rayyan, Qatar Computing Research Institute, Qatar) [17].

Data Collection and Results Synthesis

Two authors (ACAL and MQSS) independently evaluated the texts and images of the selected articles to gather the following data: authors, publication year, country, gender, age, ethnicity, symptoms, skin alterations, facial alterations, intraoral alterations, location, tooth alterations, bone alterations, maxillary sinus involvement, biopsy location, and histopathological characteristics, immunohistochemical findings, additional examinations, types of treatment, and follow-up period.

Unerupted teeth without apparent barriers as well as those impaired by primary or permanent teeth were classified as impacted teeth. In comparison to the non-affected facial side, a disproportionate and continuous lesion growth was documented.

A descriptive analysis of the main characteristics (age mean and standard deviation, absolute and relative frequencies for significant findings) was presented. A valid relative frequency of each characteristic was calculated by excluding those cases that did not inform that information. Statistical association analyses were performed on clinical variables using chi-square tests, with significance set at p < 0.05. The analyses were conducted using Jamovi (version 2.5).

Individual Risk of Bias

The assessment of bias risk and methodological quality of each article was independently performed by two authors (ACAL and MQSS) and resolved by a third author (MP) in case of disagreement. The Joanna Briggs Institute Critical Appraisal Tools [18] were used on the following questions: Q1) Were the patient’s demographic characteristics clearly described? Q2) Was the patient’s history clearly described and presented as a timeline? Q3) Was the current clinical condition of the patient on presentation clearly described? Q4) Were diagnostic tests or assessment methods and the results clearly described? Q5) Was the intervention(s) or treatment procedure(s) clearly described? Q6) Was the post-intervention clinical condition clearly described? Q7) Were adverse events (harms) or unanticipated events identified and described? Q8) Does the case report provide takeaway lessons? Not available or unclear information was considered as a “no” answer. The risk of bias rating of each article was based on the percentage of “yes” answers: high – up to 49%; moderate – between 50% and 69%; or low – over 70% [18].

Results

Study Selection

A total of 114 duplicates were excluded after initial screening of 213 records. Then, 70 out of 99 records were excluded after eligibility assessment and one record could not be retrieved [19]. After full-text reading of 30 records, seven records were excluded since they did not describe individual SOD findings [12, 20, 21], were conference papers [22, 23], referred to segmental odontomaxillary hypoplasia [24], or reported an alteration in the maxillary middle line [25].

Articles were also manually searched on the reference lists of the 23 studies that met the established inclusion and exclusion criteria [2–7, 11, 15, 26–36]. Then, 12 were additionally included in this review [8–10, 14, 37–44]. Although one study described 12 case reports, only a single case that reported the particular characteristics of SOD was included [31].

Characteristics of the Included Studies

The articles published between 1987 and 2024 detailed a total of 60 cases of SOD distributed in Brazil [27], Brazil and Chile [3], Denmark [4], Ireland [37], Israel [6], Italy [35], Jordan [44], Saudi Arabia [10], Turkey [30], United Kingdon [5, 45, 46], Uruguay [29], India [26, 34] Spain [15, 28] Canada (2,31,42), and United States of America [7, 11, 13, 14, 32, 33, 36, 38–41, 43, 47].

Individual Risk of Bias

Most of the articles showed a moderate risk of bias due to the lack of information on patients’ ethnicity (Q1) as well as treatment type and follow-up period (Q5, Q6, and Q7). Two articles did not clearly describe the diagnosis criteria (Q4) [42, 43]. The Q7 was not applicable in two articles that considered follow-up as treatment (Table 1).

Table 1.

Risk of bias and methodological quality of included articles

Article	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Risk of bias
Agrawal et al. [14]	-	✓	✓	✓	-	-	-	✓	moderate
Alakeel et al. [20]	-	✓	✓	✓	-	-	-	✓	moderate
Allen, et al. [46]	✓	✓	✓	✓	✓	✓	✓	✓	low
Alshaiji et al. [8]	-	✓	✓	✓	✓	-	-		moderate
Armstrong et al. [37]	-	✓	✓	✓	-	-	-	✓	moderate
Azevedo et al. [27]	✓	✓	✓	✓	✓	✓	-	✓	low
Becktor et al. (2002)	-	✓	✓	✓	-	-	-	✓	moderate
Bhatia et al. [5]	✓	✓	✓	✓	✓	✓	NA	✓	low
Castaño et al. [15]	-	✓	✓	✓	-	-	-	✓	moderate
Danforth et al. [11]	✓	✓	✓	✓	-	-	-	✓	moderate
DeSalvo et al. [7]	✓	✓	✓	✓	-	-	-	✓	moderate
Drake [38]	✓	✓	✓	✓	-	-	-	✓	moderate
Friedlander-Barenboim et al. [6]	✓	✓	✓	✓	✓	✓	✓	✓	low
Gavalda, (2004)	-	✓	✓	✓	-	-	-	✓	moderate
Gibson, et al. (2020)	✓	✓	✓	✓	✓	✓	-	✓	low
González-Arrigada et al. [3]	-	✓	✓	✓	-	-	-	✓	moderate
González et al. [3]	✓	✓	✓	✓	✓	✓	✓	✓	low
Heggie et al. (2019)	-	✓	✓	✓	-	-	-	✓	moderate
Jones & Ford [39]	-	✓	✓	✓	-	-	-	✓	moderate
Koenig et al. [40]	-	✓	✓	✓	-	-	-	✓	moderate
Kuklani & Nair (2010)	-	✓	✓	✓	✓	✓	NA	✓	low
Miles et al. [2]	-	✓	✓	✓	-	-	-	✓	moderate
Minett & Daley [42]	-	✓	✓	✓	-	-	-	✓	moderate
Ozpınar et al. (2008)	✓	✓	✓	-	✓	✓	✓	✓	low
Packota et al. [31]	-	✓	✓	✓	-	-	-	✓	moderate
Paticoff et al. [32]	-	✓	✓	✓	✓	-	-	✓	moderate
Porwal et al. (2008)	-	✓	✓	-	✓	✓	✓	✓	low
Prusack et al. [33]	-	✓	✓	✓	-	-	-	✓	moderate
Rai et al. [34]	-	✓	✓	✓	-	-	-	✓	moderate
Rossi et al. [35]	-	✓	✓	✓	-	-	-	✓	moderate
Smith et al. [36]	-	✓	✓	✓	-	-	-	✓	moderate
Thang et al. [45]	-	✓	✓	✓	-	-	-	✓	moderate
Whitt et al. [14]	-	✓	✓	✓	✓	-	✓	✓	low
Welsch & Stein [9]	✓	✓	✓	✓	✓	✓	✓	✓	low
Yassin & Rihani [44]	-	✓	✓	✓	-	-	-	✓	moderate

NA: not applicable

Synthesis of Outcomes

The age of the patients diagnosed with SOD ranged from 1 to 47 years (Mean of 12 ± 9.6 years). In 8 cases, the signs of the disease were noticed before diagnosis (signs were observed since birth in 5 cases). Males were more frequently affected than females (62% or 1.6:1 ratio) (Table 2). Only 20 cases reported the patient’s ethnicity: 18 Caucasian and two African American.

Table 2.

Main clinical and radiographic characteristics of SOD cases

		n	%
Gender (n = 59)	Male	36	62
	Female	23	38
Affected side (n = 60)	Right	33	55
	Left	27	45
Continuous lesion growth (n = 29)	No	17	59
	Yes	11	38
	Up to 26 years of age	1	3
Symptoms (n = 46)	No	42	91
	Yes	4	9
Facial alterations (n = 51)	Asymmetry and/or unilateral swelling	40	78
	Skin	26	50
	Lip	20	40
Intraoral alterations (n = 58)	Alveolar process enlargement	49	84
	Gingival hyperplasia	34	58
Tooth alterations (n = 60)	Absence of 1st and/or 2nd upper premolars	48	80
	Delayed teeth development and eruption	19	30
	Crown morphology	18	30
	Root morphology	18	30
	Primary tooth root resorption	16	27
	Tooth displacement	36	61
Bone alterations (n = 52)	Increased density	36	69
	Altered Trabecular pattern	36	69
	Vertically oriented trabecular bone	14	27
Maxillary sinus involvement (n = 46)	Yes	41	89
	No	5	11
Treatment (n= 33)	Teeth extaction	10	30
	Orthodontics	12	36
	Implant	4	12
	Endodontics	1	3
	No treatment	7	21

Cases without available information were excluded from the analysis

Most SOD cases occurred in the maxilla and 55% affected the right side. Three cases reported similar alterations both in the maxilla and mandible, in the same side [13, 45]. Continuous lesion growth was observed in 11 cases, while growth proportional to the patients’ normal facial development was reported in 17 cases. One patient presented with continuous lesion growth until the age of 26 [11]. The great majority of the cases (91%) were asymptomatic. Two patients reported pain, gingival swelling, and drainage [29, 33]. In two cases pain was reported [46, 47].

Most cases (78%) were characterized by facial asymmetry and/or unilateral swelling. Among the 26 patients that presented with skin alterations, hyperpigmentation and pigmented nevus were respectively reported in 10 and 3 cases (Supplementary material 3). Hypertrichosis and erythematous areas were observed in 18 and 6 patients, respectively. Twenty patients presented with some type of lip alteration: swelling (6), commissural clefting (4), upper lip hypopigmentation (4) or hyperpigmentation (2), indistinct mucocutaneous upper lip border (2), upper lip asymmetry and protrusion (3). two patients did not present facial alterations, and this information was not reported in nine cases (Supplementary material 3).

Intraoral alterations mainly comprised unilateral maxillary alveolar process enlargement (84%) and gingival hyperplasia (58%). All patients presented with tooth alterations, and the absence of the 1st and/or 2nd upper premolars was reported in 44 cases (80%). Absences of primary and permanent molars and canines were also observed (Supplementary material 4). Delayed teeth development and eruption were reported in 18 cases (30%). Tooth displacements were reported in 36 cases (61%), in which abnormal tooth spacing and distalization were observed in 31 patients. Alterations in the crown morphology (mainly enamel hypoplasia) were observed in 18 cases. Alterations in the root morphology and atypical root resorption in primary teeth were observed in 18 patients (30%). The radiographic appearance of the maxillary bone was mainly described as a dense area (69%). Trabecular pattern alteration and trabecular vertical orientation were reported in 36 (69%) and 14 (27%) patients, respectively. Alteration of the maxillary sinus contour or volume reduction was present in 41 cases (89%) and absent in five cases (12%).

Biopsy was performed to diagnose 39 cases, which was mostly performed in the alveolar bone and soft tissue and revealed dense trabecular bone with prominent reversal lines, absence of osteoblast and osteoclast activity, absence of inflammation, fibrous and myxoid stroma, and gingival tissue hyperplasia (Supplementary material 4). The involved teeth were biopsied in two cases and revealed an irregular dentin outline near the pulp chamber [27, 42] The biopsy of the hyperpigmented skin area revealed acanthosis and increased basilar hyperpigmentation [9, 39]. In one case, the biopsy of a hyperpigmented patch was suggestive of Becker’s nevus [10].

Seven patients were only followed up without intervention and 26 cases reported some type of treatment [3–5, 33, 41], which included endodontic treatment [36], tooth extraction [3, 4, 14, 27, 30, 32, 36, 46, 47], orthodontics [13, 14, 29, 32, 36, 43], genioplasty [6, 14], surgical reduction of alveolar bone volume [8, 14], implants [4, 8, 14], and prosthetic rehabilitation [27, 30, 43]. Three cases treated with implants reported normal osseointegration [4, 14] while one study did not report the implant treatment outcome [8]. Six out of 12 cases reported no complications or adverse events during orthodontic treatment [3, 13, 14, 29, 36, 43]. In three cases, gingivoplasty was required to place orthodontic appliances [14, 36]. The involved teeth moved slowly in one case [14] and the alveolar bone did not follow the traction-induced tooth extrusion in another case [29]. The orthodontic treatment outcome was not reported in two cases [14, 32]. Follow-up was reported in 19 cases and ranged from 0.5 to 21 years (mean of 6.9 ± 5.4 years).

It was possible to perform association analyses between some of the evaluated variables. No statistically significant association was found between gender and the presence of facial asymmetry (p > 0.05). Similarly, there was no statistically significant association between gender and continuous lesion growth (p = 0.242). The association between the affected side and continuous lesion growth also did not reach statistical significance (p = 0.083), suggesting that the available data are not sufficient to confirm this relationship conclusively. Additionally, no statistically significant association was observed between the presence of intraoral alterations and continuous lesion growth (p = 1.0). Similarly, the analysis between the presence of symptoms and continuous lesion growth indicated that these variables are independent of each other.

Discussion

The analysis and synthesis of the available evidence of SOD is essential to understand its main characteristics (clinical, radiographic, and histopathological) and describe treatment options. This study systematically reviewed 60 SOD cases with a mean patient age of 12 years and that mainly affected Caucasian males. All SOD cases occurred in the maxilla and presented with tooth alterations. Although a few cases reported pain, gingival swelling, and drainage, most patients were asymptomatic, and signs were often observed before diagnosis. A dense maxillary bone appearance, trabecular pattern alterations, vertical trabecular orientation, and reduction of the maxillary sinus volume were the main radiographic findings in most of the cases. Moreover, skin pigmentation and texture alterations were observed in 50% of SOD cases.

Due to overlapping symptoms, it is very important to address the differential diagnosis between SOD and fibrous dysplasia (FD) since their treatment is fundamentally different [11, 41]. FD can cause tooth displacement, malocclusion, and eruption delay, while SOD is frequently associated with the absence of upper premolars, alterations in teeth crowns and roots, and tooth displacement [4]. The continuous lesion growth induced by both disorders can cause facial asymmetry, maxillary bone expansion, and swelling [14]; in addition, an increased bone density and altered trabecular patterns are observed in radiographs [41].

FD potentially affects multiple bones (long bones, ribs, and skull) while SOD is restricted to a specific segment of the maxillary bone [11, 14]. Histologically, SOD does not display the typical features of FD in which irregularly shaped individual bony trabeculae are formed in a rather cellular, loosely arranged fibrous stroma [4]. In FD cases, normal bone is replaced by fibrous tissue containing irregular trabeculae of vital woven bone, which resembles “Chinese characters” without numerous reversal lines and typically presents significant osteoid rimming [41]. Conversely, SOD presents dense trabecular bones with prominent reversal lines and without significant osteoblastic or osteoclastic activity and inflammation [41].

Detailed knowledge of SOD allows clinicians to diagnose early and plan appropriate treatments for aesthetic needs resulting from facial asymmetry and unilateral swelling [2, 4–9, 11, 14, 26, 28, 31–34, 37, 39, 41]; in addition, tooth alterations such as premolars absence and teeth displacements can lead to chewing and speaking difficulties that also require adequate treatments [3, 5, 6, 11, 14, 33, 36].

Due to the variability of clinical signs and the lack of specific treatment protocols [41], the management of SOD cases ranges from follow-up without intervention [3–5, 33, 41] up to invasive dental treatments such as endodontics of primary teeth [36], tooth extractions [3, 4, 14, 27, 30, 32, 36], orthodontics [14, 29, 32, 36, 43], and surgery for alveolar bone volume reduction [8, 14]. Implants were also placed and showed normal osseointegration in three out of four cases [4, 8, 14]. However, the varied approaches and patient responses highlight the need for individualised treatments; in addition, clinicians must be aware of possible complications such as continuous adjustments during orthodontic treatment [14, 29, 32, 36, 43]. Definitive treatment is often postponed until after the pubertal growth spurt and the few number of cases involving adults suggests spontaneous regression with age [41]. Detailed reporting and long-term following-up of SOD cases are needed to improve scientific evidence regarding etiology and complications as well as to develop effective treatment protocols.

One limitation of this study is related to the fact that the WHO only recently established diagnostic criteria for SOD [1]. Consequently, the diagnoses of the cases included in this systematic review did not follow uniform criteria. Nonetheless, all the cases exhibited clinical and radiographic features consistent with those originally described by Miles et al. in 1987 [2]. Another limitation is that this review includes only cases where individual characteristics were sufficiently detailed to allow for statistical analysis. As a result, the number of cases reported here may not represent the full spectrum of cases documented in the literature. All excluded cases have been detailed in the results section to ensure transparency.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Author Contributions

All authors contributed to the study conception and design. Literature search and data collection and analysis were performed by A.L., G.L., M.M., A.F. and M.S. The first draft of the manuscript was written by A.L. Research was supervised by J.L.C.J and M.Q.S.S. All authors read and approved the final manuscript.

Funding

This study was not supported by any funding.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Ethical Approval

This article does not contain any studies with human participants performed by any of the authors.

Consent to Participate

For this type of study informed consent is not required.

Consent for Publication

For this type of study consent for publication is not required.

Competing Interests

The authors declare no competing interests.