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| CASE REPORT |
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| Year : 2022 | Volume
: 34
| Issue : 4 | Page : 484-487 |
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“Fruit in a tooth” - A rare non - Syndromic anomaly - 2 rare case reports with a genetic analysis
Arul Jothi Murugan, G Anuradha, A Kannan, Krithika Chandrasekar Lakshmi
Department of Oral Medicine and Radiology, SRM Dental College, Ramapuram, Chennai, Tamil Nadu, India
| Date of Submission | 11-Mar-2022 |
| Date of Decision | 13-Jun-2022 |
| Date of Acceptance | 23-Oct-2022 |
| Date of Web Publication | 09-Dec-2022 |
Correspondence Address:
Arul Jothi Murugan
Department of Oral Medicine and Radiology, SRM Dental College, Ramapuram, Chennai, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jiaomr.jiaomr_84_22
 Abstract | | |
Tooth agenesis is one of the most common developmental anomalies affecting function and aesthetics. Genetic mutations cause non-syndromic tooth agenesis and involve the interaction of genes of tooth epithelium and mesenchyme odontogenesis. This article is the first in the literature to present non-syndromic cases of two siblings reported with mulberry molars, morphological changes in teeth (hypodontia and microdontia), and a genetic study performed to substantiate the involvement of Paired box gene 9 in tooth agenesis and morphogenesis.
Keywords: Developmental defect, genetic mutation, mulberry molar, PAX9Key Message: Genes interact with the tooth epithelium and mesenchyme during their development, and genetic mutation can cause non-syndromic tooth anomalies and agenesis.
How to cite this article:
Murugan AJ, Anuradha G, Kannan A, Lakshmi KC. “Fruit in a tooth” - A rare non - Syndromic anomaly - 2 rare case reports with a genetic analysis. J Indian Acad Oral Med Radiol 2022;34:484-7 |
How to cite this URL:
Murugan AJ, Anuradha G, Kannan A, Lakshmi KC. “Fruit in a tooth” - A rare non - Syndromic anomaly - 2 rare case reports with a genetic analysis. J Indian Acad Oral Med Radiol [serial online] 2022 [cited 2023 Jan 28];34:484-7. Available from: http://www.jiaomr.in/text.asp?2022/34/4/484/363038 |
| Introduction | |  |
Non-syndromic (NS) tooth agenesis is the most common congenital disorder, with a prevalence of 2.2% to 10.1% in the general population, when third molars are excluded.[1] Evidence is available that environmental and genetic factors are responsible for tooth agenesis. Mutations of several genes have been identified in patients with tooth agenesis. Among the many genes, Heterozygous mutations of PAX9 show several familial, non-syndromic cases.[2]
This article focuses on reporting the rare occurrence of mulberry molars in a non-syphilitic, non-syndromic condition of two siblings with gene workup.
Timeline history:
| Case Report | | |
An 18-year young female reported the unaesthetic appearance of upper front teeth from childhood. Extraoral examinations and medical and personal history were non-contributory. The patient gave a history of hyperhidrosis, and her mother denied any history of Congenital syphilis and other infection during pregnancy. Her family history was positive with her younger sister, aged 15. Morphological changes were noted from the time of eruption of the first permanent molar teeth.
Case 1
Intraoral examination revealed multiple globular projections in permanent molars, irregular shovel-shaped incisors, multiple retained deciduous teeth, a few congenitally missing permanent teeth, and microdontia. The premolars resembled molars with extra cuspal projections. No soft tissue abnormalities were found [Figure 1]a, [Figure 1]b, [Figure 1]c. | Figure 1: (a) Jpg shows an intraoral picture of Case 1 – the unaesthetic appearance of upper front teeth. (b and c) Jpg shows an intraoral picture showing globular cusps, shovel-shaped incisors
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Case 2
Sibling also showed the presence of mulberry permanent molars, microdontic teeth, retained primary lower central incisors and missing permanent lateral incisors, and upper right second molar teeth [Figure 2]a, [Figure 2]b, [Figure 2]c.
Investigations
Panoramic images of both cases showed an increase in thickness of the enamel, single conical roots, retained primary teeth of lower central incisors, and left upper lateral incisors. The permanent tooth germs of the abovementioned primary teeth were absent. Permanent second molars, right upper lateral incisors, and permanent lower canines were missing [Figure 3]a and [Figure 3]b.
Gene expression study
For a genetic defect to cause dental anomalies restricted to teeth, the defective gene is critical for proper dental development. Heterozygous mutations of PAX9 show several familial, non-syndromic cases.[1]
With informed consent, 5 ml of venous blood was drawn from the patient, stored on an ethylenediamine tetraacetic acid vacutainer, and sent for PAX9 gene analysis. Ribonucleic acid (RNA) was extracted from the collected sample after multiple centrifuges. Extracted RNA mix was thawed, subjected to centrifuge, and incubated at 50°C for 60 min, heated at 70°C for 10 min, cooled to 4°C, and stored at −20°C to obtain cDNA. The prepared reaction mix was mixed thoroughly and added to PCR tubes to which DNA (≤500 ng/reaction) is added to individual PCR tubes then they are placed in a real-time cycler, and cycling is started [Figure 4]a. | Figure 4: (a) Jpg shows primer used for gene analysis. (b) Jpg results showing down-regulation of PAX9 gene
Click here to view |
| Results | | |
Expression of PAX9 Gene is slightly downregulated in our case [Figure 4]b.
Correlating all the findings, a final diagnosis of rare non-syndromic, non-syphilitic tooth anomaly with PAX9 gene involvement was confirmed.
Differential diagnosis based on clinical findings, includes congenital syphilis, enamel hypoplasia, and ectodermal dysplasia.
Siblings were referred for cosmetic treatment. They underwent endodontic treatment followed by veneers for anterior teeth. Patients are under treatment with follow-up.
| Discussion | | |
Teeth are specialized structures comprising enamel, dentin, and cementum. Developmental defects occurring in these mineralized tissues are either alone (isolated), or in combination (syndromic) with defects in other organs or tissues.
In our study, the siblings reported mulberry molars affecting permanent molars with no history of fever, syphilis, or any other infections during intrauterine life. The etiology is multifactorial, certainly related to local, systemic, genetic, or environmental factors. Mulberry tooth is a common feature of congenital syphilis and our report aids literature evidence of the rare occurrence of mulberry molars in non-syphilitic, non-syndromic conditions.
Enamel is most susceptible to changes in the environment, causing developmental changes in permanent dentition. The permanent first molar demonstrates huge variations in their morphological features like anomalous cusps and variations in the occlusal surface showing globular-shaped cusps.[3]
In the present case, occlusal anatomy was irregular, with multiple globular projections involving all four permanent molars resembling mulberry molars.
Koneru et al. reported a similar case in 2019, which had an occurrence of multiple globular cusps resembling mulberry molars in non -syphilitic conditions.[4]
Mulberry molars are characterized by a grossly deformed crown imitating mulberry fruit frequently seen as congenital syphilis.[4] These discrepancies can be due to enamel hypoplasia or its deficiency. The underlying dentin and pulp are normal, while the enamel is thin and deformed.[4]
Sedano et al. reported a 15-year-old female with dens invaginatus, mulberry molars, and various other morphological changes, and discussed genetic considerations.[3]
Microdontia, macrodontia, and conoid teeth represent variations in crown morphology that in some families are inherited traits.[3]
Several genes participate in the development of teeth, the following five genes [e.g., [Table 1]] could be responsible for the dental anomalies in our case.[5]
Afshar et al. reported that enamel hypoplasia or hypo calcification of the first permanent molars is more common in infants born in the cesarean section delivery (C/S) than those born in normal vaginal delivery.[9]
In the present case, the history of normal delivery and absence of infection during pregnancy rules out congenital syphilis, and the occurrence of mulberry molars can be considered as the non -syphilitic occurrence of mulberry molars.
Ectodermal dysplasia is considered for differential diagnosis as the patient showed multiple missing and morphological changes of teeth and hyperhidrosis.[7]
Our study is novel as it advocates 2 cases with PAX9 gene downregulation causing morphological changes and tooth agenesis. The rare occurrence of non-syphilitic, non-syndromic mulberry molars, and PAX9 gene expression implies clinicians think outside the box and provides insight to consider genetic investigation during similar clinical scenarios. The genetic workup if done for all family members could have provided strong literature evidence advocating the involvement of PAX9 in tooth agenesis.
| Conclusion | | |
The reported cases were unique with infrequent pathology and varied morphological changes in teeth requiring a multidisciplinary approach. This case report opens the vision to see a few conditions/anomalies from different perspectives paving the way to notice underlying genetic causes.
Patient perspective
The patient was gratified for the information they gained with genetic analysis as they were not aware of the genetic condition inherited in their family.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Wong S-W, Han D, Zhang H, Liu Y, Zhang X, Miao MZ, et al. Nine novel PAX 9 mutations and a distinct tooth agenesis genotype-phenotype. J Dent Res 2017;97:155-62.  |
| 2. | Kist R, Watson M, Crosier M, Robinson M, Fuchs J, Reichelt J, et al. The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells. PLoS Genet 2014;10:e1004709. |
| 3. | Sedano HO, Ocampo Acosta F, Naranjo Corona RI, Torres Arellano ME. Multiple dens invaginatus, mulberry molar and conical teeth: Case report and genetic considerations. Med Oral Pat Oral Cir Bucal 2009;14:E69-72. |
| 4. | Koneru A, Hunasgi S, Manvikar V, Vanishree M. Nonsyphilitic occurrence of mulberry molars: A rare case report. J Oral Maxillofac Pathol 2019;23:106-10. [ PUBMED] [Full text] |
| 5. | Fauzi NH, Ardini YD, Zainuddin Z, Lestari W. A review on non-syndromic tooth agenesis associated with PAX9 mutations. Jpn Dent Sci Rev 2018;54:30-6. |
| 6. | Jumlongras D, Bei M, Stimson JM, Wang W-F, DePalma SR, Seidman CE, et al. A nonsense mutation in MSX1 causes Witkop syndrome. Am J Hum Genet 2001;69:67-74. |
| 7. | Anuradha G, Kumar G, Kavitha M. A case report and brief review of ectodermal dysplasia-a clinical rarity. J Clin Den Upd Res 2014;4:21-3. |
| 8. | Green PD, Hjalt TA, Kirk DE, Sutherland LB, Thomas BL, Sharpe PT, et al. Antagonistic regulation of Dl x2 expression by PITX2 and Ms×2: Implications for tooth development. Gene Expr 2001;9:265-81. |
| 9. | Afshar H, Seraj B, Emadosadati A. An investigation on the relationship between the type of delivery and enamel defects of the first permanent molars. J Data Med 2003;16:46-52. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1]
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