CASE REPORT |
https://doi.org/10.5005/jp-journals-10005-2539 |
A Rare Incidence of Nonsyndromic Mandibular Incisor Agenesis in a Three-generation Family: Case Report and Literature Review
1Department of Dentistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2Department of Orthodontics, All India Institute of Medical Sciences, Jammu, Jammu & Kashmir, India
3,4Department of Orthodontics and Dentofacial Deformities, Centre for Dental Education and Research, All India Institute of Medical Sciences, Delhi, India
Corresponding Author: Vilas D Samrit, Department of Orthodontics and Dentofacial Deformities, Centre for Dental Education and Research, All India Institute of Medical Sciences, Delhi, India, Phone: +91 9899503560, e-mail: vilassamrit@gmail.com
ABSTRACT
Hypodontia is an inherited condition involving the absence of one to six teeth. The permanent dentition is the most frequently affected; however, it may also affect the primary dentition. A congenitally missing tooth (CMT) is the most common dental abnormality, with the missing mandibular second premolar, maxillary lateral incisor, maxillary second premolar, and mandibular central incisor accounting for 90% of CMT in hypodontia studies. The etiology of CMT has been attributed to environmental and genetic contributing factors, with the latter having a strong influence. It may occur in isolation or in association with syndromes. Congenitally missing mandibular incisor is more common in the Asian population and females. Depending on the number and location of missing teeth, hypodontia may be a considerable issue for the clinician since it may impact occlusal balance, mastication, speech, and esthetics and often requires a multidisciplinary approach. Missing mandibular incisors are of particular interest to orthodontists because of the possibility of mandibular retrognathism, the potential for the development of malocclusion, and difficulty in achieving a balanced occlusion. This case report describes the skeletal and dental features of a nonsyndromic familial occurrence of missing mandibular incisors in three generations. A comprehensive literature search was also performed to review the familial cases with missing mandibular incisors.
How to cite this article: Selvaraj M, Sennimalai K, Samrit VD, et al. A Rare Incidence of Nonsyndromic Mandibular Incisor Agenesis in a Three-generation Family: Case Report and Literature Review. Int J Clin Pediatr Dent 2023;16(2):388–395.
Source of support: Nil
Conflict of interest: None
Keywords: Congenitally missing teeth, Familial tooth agenesis, Hypodontia, Mandibular incisor
INTRODUCTION
Tooth agenesis is one of the most prevalent developmental disturbances of permanent dentition.1,2 Hypodontia (OMIM #106600) is the congenital absence of one to six teeth with a population prevalence of 6.4%.2-4 It is observed that mandibular second premolars are the most commonly missing teeth, followed by maxillary lateral, maxillary second premolars, mandibular central incisors, and mandibular lateral incisors.5 There are ethnic variations reported in prevalence as well as the type of teeth affected. Prevalence is highest in Africa (13.4%), followed by Europe (7%) and Asia (6.3%).6 Mandibular second premolars are most affected in the Caucasian population, whereas mandibular incisors are commonly involved in Asian Populations.7-9 Females have a higher prevalence than males.5 It could be attributed to their smaller jaws, which might interfere with tooth bud formation.10
Congenitally missing teeth (CMT) may occur as an isolated entity or a component of a syndrome. Also >60 syndromes have been known to be associated with this condition.4,11 The etiology of tooth agenesis is often a genetic cause, with an autosomal dominant pattern of transmission, incomplete penetrance, and variable expressivity.12 According to Graber, “It’s the dental clinician’s challenge to recognize the congenital absence of teeth and evaluate other family members for possible manifestations of this primary inheritable condition.”13 With just a few cases previously recorded, hereditary or familial transmission has been considered the main cause of mandibular incisor agenesis.13-15 The other possible causes may include disturbances in mandibular symphysis development leading to congenital absence of lower incisor tooth bud or a manifestation of an evolutionary trend.13,14 Various studies reported mandibular incisor agenesis in two-generation and among siblings.13,16,17 However, only one incidence was reported in the literature with a missing mandibular incisor in a three-generation Japanese family.18 This paper reviews the literature on nonsyndromic familial mandibular incisor agenesis cases and reports the condition in a three-generation family.
CASE DESCRIPTION
An 11-year-old boy of North Indian ethnicity and the first child of healthy nonconsanguineous parents presented to the orthodontic clinic with the chief complaint of spacing between the upper and lower teeth. Medical history was noncontributory, and the patient’s dental history was uneventful. In addition, there was no history of infection, trauma, or drug therapy throughout the mother’s pregnancy. There was a history of normal delivery at term, and neonatal history was noncontributory. The family history revealed that both his father and grandfather have agenesis of permanent mandibular incisors and retained deciduous teeth.
The patient’s height, weight, and build on general examination correlated with his chronological age. There was no delay in achieving the developmental milestones. History revealed mouth breathing habits, particularly during sleep. The extraoral features showed an apparently symmetrical face with potentially competent lips, a deep mentolabial sulcus, and a prominent chin. Intraoral examination revealed that the patient was in the late mixed dentition stage. The maxillary incisors were proclined with generalized spaces between them. The mandibular central incisors were missing clinically with an over-retained deciduous incisor. The molar was in half-cusp Class II relation bilaterally. There was a 9 mm overjet and a traumatic deep bite (100% overbite) with lower incisors impinging on the palatal surface (type 1 Akerly classification). The dental arches were symmetrical. The palate was deep, with an exaggerated curve of Spee in the mandibular arch. The frenal attachments were normal, with no soft tissue abnormalities. The oral hygiene was satisfactory except for proximal caries in the deciduous maxillary left second molar. The panoramic radiographic confirmed the congenital absence of the mandibular central incisors and all the third molar tooth buds. The lateral cephalogram showed enlarged adenoids, retrognathic mandible, steep mandibular plane, proclined upper incisors, prominent chin, and retrusive lips (Fig. 1).
Figs 1A and B: (A) Extraoral and intraoral clinical photographs and panoramic radiograph of the patient (proband); (B) cephalometric radiograph and tracing of the patient
The patient’s 41-year-old father had a congenitally missing permanent mandibular central incisor with a retained deciduous mandibular incisor tooth that was mobile. The molar relation was Angle’s Class I with proclined incisors. The skeletal base was Class I with a prominent chin button, deep mentolabial sulcus, and retrusive lips (Fig. 2). Likewise, the patient’s 66-year-old grandfather had congenitally missing permanent mandibular central incisors and a mobile retained deciduous mandibular incisors. The molar relation was Angle’s Class I bilaterally with age-related changes such as attrition of teeth and interdental spacing. The skeletal bases were in Angle’s Class I relationship with a flat mandibular plane. The incisors were retroclined, and the lips were thin and retrusive (Fig. 3). Both were medically fit, and no contributing history or condition was present that was relevant to their missing permanent mandibular central incisors. The pedigree analysis revealed that the trait that is, congenitally missing mandibular incisors, was present in all three generations with the male-to-male transmission, essentially showing an autosomal dominant inheritance pattern. The developmental history and a thorough dysmorphic physical examination by a clinical geneticist did not reveal any other congenital deformity; therefore, a provisional diagnosis of a nonsyndromic condition was made in all three cases. Further, the family was not made to undergo additional genetic testing due to financial constraints.
Figs 2A and B: (A) Extraoral and intraoral clinical photographs and panoramic radiographs of the patient’s father; (B) Cephalometric radiograph and tracing of the patient’s father
Figs 3A and B: (A) Extraoral and intraoral clinical photographs and panoramic radiographs of the patient’s grandfather; (B) cephalometric radiograph and tracing of the patient’s grandfather
LITERATURE REVIEW
The literature search on familial cases of mandibular incisor agenesis was conducted using various databases (PubMed, Embase, Scopus, Web of Science, and Ovid MEDLINE) till March 2022 with no language or time restrictions. The search terms used in various databases were (“lower incisor” or “mandibular incisor” or “mandibular anterior” or “lower anterior”) and (hypodontia or “missing” or “agenesis” or anodontia or oligodontia or absent) and (congenital or familial or genetic or hereditary) and (“nonsyndromic” or non-syndromic). Only articles with the familial occurrence of missing mandibular incisors were included in this study. In addition, articles in which patients had a history of extracted permanent mandibular incisors, impacted mandibular incisors, missing primary mandibular incisors, history of facial trauma, craniofacial anomalies, and syndromes were excluded. A search through various databases yielded a total of 292 studies. Out of these 292 articles, 115 articles were screened after removing duplicates. Based on titles and abstracts, 33 full-text articles were reviewed. Of these 33 articles, 29 had nonfamilial/generation, syndromic, and multiple missing teeth and did not meet the selection criteria. Lastly, four articles were considered after a full-text review (Flowchart 1).13,16-18 The following data were extracted—author, year of publication, number and age of patients, gender, race/ethnicity, missing teeth, malocclusion, affected family members, and other findings (Table 1). The two authors (MS and KS) performed the study identification and data extraction and were reviewed by the senior authors (VS and RD).
Flowchart 1: Flow diagram illustrating the search process
| Author (Year) | Generations affected | Family members affected | Race | Age | Missing teeth | Other findings |
|---|---|---|---|---|---|---|
| Miller et al. (1941)18 | Three generations | Grandmother, mother and one son and daughter | Japanese | Not known | Single mandibular lateral incisor in all the three generations | Not known |
| Newman et al. (1998)13 | Two generations | Mother and three daughters | Indian | 9 years (daughter 1) | Two mandibular incisors | Third molars absent |
| 10 years (daughter 2) | Mandibular left central incisor | – | ||||
| 12 years (daughter 3) | Mandibular left incisor | Third molars absent | ||||
| 26 years (mother) | Mandibular left incisor | – | ||||
| Frazier-Bowers et al. (2003)16 | Eleven families (16 out of 20 patients had at least one first degree relative affected) | Variable | Vietnamese | Age ranging from 5 to 32 years | Around 10 patients had bilateral mandibular incisor missing. Remaining 10 patients had single incisor missing | Third molar absent in one patient. Class III molar relation in most of the patients |
| Korkut et al. (2016)17 | Two generations | Daughter, siblings and father | Not reported | 9 years (daughter–proband) | Bilateral mandibular central incisors | Premature birth missing second premolars and molars and upper first molar |
| Not reported (siblings) | Bilateral mandibular central incisors | – | ||||
| Not reported (father) | Bilateral mandibular central incisors | – | ||||
| Two generations | Son and father | Not reported | 9 years (son–proband) | Bilateral mandibular central incisors | – | |
| Not reported (father) | Mandibular central incisors | – | ||||
| Current study | Three generations | One family (grandfather, father, and son) | Indian | 11 years (son–proband) | Bilateral mandibular central incisor | Retained deciduous mandibular incisor and Class II skeletal base |
| 41 years (father) | Mandibular central incisor | Retained deciduous mandibular incisor | ||||
| 66 years (grandfather) | Bilateral mandibular central incisor | Retained deciduous mandibular incisors |
Miller et al. reported three generations of missing one mandibular incisor in a Japanese family. Based on pedigree analysis, autosomal dominant inheritance was suggested. The congenital absence of missing teeth was confirmed using an intraoral periapical radiograph.18 Newman et al. reported a case of an Indian mother and her three daughters with congenitally missing mandibular incisors. All of them displayed a relatively balanced facial profile on extraoral assessment; however, the cephalometric study revealed the lower jaw to be retruded. Besides, one of the daughters had an Angle’s Class III subdivision molar relationship, while the others had Angle’s Class I molar relationships. The treatment of missing mandibular incisors by orthodontic space closure was described.13 Frazier-Bowers et al. screened records of 700 people of Vietnamese descent in the age group of 5–49 years. A total of 20 patients were identified, comprising eight male and twelve female patients. A total of 16 patients had a familial history of at least one affected first-degree relative. Around 10 patients showed bilateral mandibular only one presented with missing maxillary third molars. The affected patients also showed morphological variations—12 had shovel-shaped incisors, and one presented with a fusion of primary teeth (72 and 73). Fifteen patients had a Class III occlusal relationship, possibly due to mesial migration of the mandibular posterior teeth consequent to incisor hypodontia. Pedigree analysis showed an autosomal dominant inheritance with incomplete penetrance. Based on the mutational analysis of paired box 9 (PAX9) and msh homeobox 1 (MSX1), it was uncertain whether these genes caused mandibular incisor agenesis in this population.16 Korkut et al. presented two cases (one male and one female) with the familial transmission of a bilaterally missing mandibular incisor. Father and siblings were also affected by the same condition. Additionally, the female patient presented with multiple congenitally missing teeth.17
DISCUSSION
Congenitally missing teeth (CMT) is a dental disability affecting personal appearance, functional problems and overall quality of life.19,20 Several explanations have been proposed to explain the cause of tooth agenesis. The most mesial tooth in each field are considered more genetically stable, but the teeth at the end of each field are less genetically stable and thus more likely to get affected.21 Role of evolution has also been proposed, which states that the evolutionary process produces a steady decline in human dentition as each quadrant loses a tooth.10,22 Apart from the genetic influence and evolutionary mechanism, environmental factors such as endocrine disorders, local trauma, and radiation have been implicated in the etiology of hypodontia.3 Early odontogenesis is influenced by several overlapping molecular processes during the signal transduction between the epithelium and neural-crest-derived mesenchyme.23,24 High levels of oxidative stress can affect the neural cells, disrupting these odontogenesis processes.25 Children receiving radiation and chemotherapy have also been linked to the occurrence of hypodontia.26 Additionally, thalidomide embryopathy (7.7%) has a higher prevalence than normal children (0.4%).27,28
Nonsyndromic tooth agenesis is one of the most common dental problems; however, it can also be associated with various syndromes, including van der Woude syndrome, ectodermal dysplasia, oromandibular limb hypogenesis syndromes and hypoglossia-hypodactyly or Hanhart’s syndrome.29,30 Selective tooth agenesis is known to be associated with variants of PAX9, ectodysplasin A (EDA), MSX1, ectodysplasin A receptor (EDAR) associated death domain, wingless-type Mouse mammary tumor virus integration site family member 10A (WNT10A), bone morphogenetic protein 2 (BMP2), EDAR, axis inhibition protein 2 (AXIN2), DAN family BMP antagonist (GREM2) and gremlin 2.7,27,29,31,32 Defects in MSX1 and PAX9 appear particularly sensitive to posterior teeth.33 On the other hand, it has been demonstrated that autosomal-dominant AXIN2 mutations can lead to a severe type of multiple-tooth agenesis. In contrast, EDA variants can cause hypo-hidrotic ectodermal dysplasia, and nonsyndromic tooth agenesis favors the anterior dentition.3,34 During the bell stage of lower incisor formation, BMP2 is expressed, and single nucleotide mutations in the gene are thought to enhance the chance of mandibular incisor agenesis.7 As a result, the varying sensitivity of distinct dentition types could be influenced by the variable expression of associated genes, indicating differing roles for these genes during normal tooth development.
In Chinese individuals with nonsyndromic hypodontia, Wang et al. discovered two unique missense variants in the PAX9 gene. Both mutations (G6R and S43K) are found in PAX9’s paired domain and are likely to disrupt amino acid residues that are highly conserved. G6R mutations were linked to missing mandibular incisors, while S43K mutations were related to multiple missing teeth.35 Yamaguchi et al. determined the genetic causes of selective mandibular incisor agenesis (SMIA), which is common in Asian populations. Exome analysis revealed variations in the genes EDA, AXIN2, PAX9, BMP2, WNT10A, and EDAR linked to tooth agenesis. In addition, the lately discovered genes such as family with sequence similarity 65 member A, nuclear factor of activated T-cells 3, and cadherin-related 23 gene have been linked to SMIA.7
Mandibular incisor agenesis significantly impacts the growth and shape of the mandibular symphysis. The constant growth of the mandibular symphysis, which results in vertical and horizontal development, is facilitated by tooth eruption.36 A disruption in tongue-lip pressure balance and a loss of lingual support are also outcomes of agenesis of both mandibular incisors, further leading to mandibular retrognathia associated with a severe anterior deep bite.14 Noncoinciding dental midline and often broad spacing in the anterior area contribute to an unattractive appearance. In different studies, the association between tooth agenesis and craniofacial morphology has generated conflicting results. However, sagittal skeletal relationships are minimally affected by missing mandibular incisors.37 Disturbances in tooth morphology and size, hypoplastic enamel, delayed eruption, prolonged retention of primary teeth, tooth impaction or eruption, and transposed teeth due to migration abnormalities are often associated with dental malformations linked with hypodontia.11
Our report describes a rare familial occurrence of mandibular incisor agenesis in three generations of people with intact retained deciduous incisors. There was no syndromic relationship in the clinical evaluation of the patient and their family members. However, the importance of genome sequencing in detecting any abnormalities cannot be overlooked. In such cases, genome sequencing aims to detect any AXIN2 gene-like variations linked to intestinal polyposis and colorectal cancer.7 The proband patient showed the features of mandibular retrognathia. However, the facial balance in the father and grandfather revealed that the mandibular retrognathia in the proband patient could be due to environmental causes such as increased resistance in nasal breathing leading to chronic mouth breathing.38 The interception of habit followed by unlocking the mandible is the first line of treatment in such patients. Calculating the Bolton ratio and virtual setup may help orthodontic treatment planning and predict future arch coordination.39 If orthodontic space reopening is performed, a temporary removable partial denture may be advised to serve the purpose of retainer and space maintainer until a definitive prosthesis is planned. The congenital absence of mandibular incisors can result in atrophy of the anterior alveolar bone ridge, which could be disadvantageous to placing an endosseous prosthetic implant.40 For this reason, orthodontic space opening for prosthetic placement is avoided during the mixed dentition stage. Treatment planning should be based on the patient’s age, facial morphology, the amount of molar and incisor correction required, alveolar bone status, and the patient’s desire.
CONCLUSION
A familial case of congenitally missing mandibular incisors is a sporadic condition. The cause of nonsyndromic tooth agenesis is multifactorial but most commonly due to genetic variation; however, the specific genes responsible for mandibular incisor agenesis have not been identified. A prompt diagnosis based on history, clinical examination, radiographic evaluation, and the patient’s realistic expectations should be the foundation for treatment planning. Genetic testing may be warranted in cases showing familial tooth agenesis to exclude any syndromic association or predict risk for disease such as adulthood neoplasms.
ETHICAL STATEMENT
Informed written consent was obtained from the patients and guardians to publish their photographs and radiographs.
ORCID
Madhanraj Selvaraj https://orcid.org/0000-0002-2150-6022
Karthik Sennimalai https://orcid.org/0000-0001-6926-3691
Vilas D Samrit https://orcid.org/0000-0002-1475-4407
Ritu Duggal https://orcid.org/0000-0002-2480-6039
ACKNOWLEDGMENTS
We thank the patients for consent to use their treatment records.
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