- Email: [email protected]
Non syndromic familial tooth agenesis—A case report and overview of genetic factors
G Model JOMSMP-243; No. of Pages 3
ARTICLE IN PRESS Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Non syndromic familial tooth agenesis—A case report and overview of genetic factors Shaik Mohamed Shamsudeen SS, Nalin Kumar S, Sujatha G, Muruganandhan J ∗ Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Off OMR, Thalambur, Chennai 603103, Tamil Nadu, India
a r t i c l e
i n f o
Article history: Received 24 September 2013 Received in revised form 12 November 2013 Accepted 20 November 2013 Available online xxx
a b s t r a c t Tooth agenesis is one of the most common anomalies of the human dentition characterized by the developmental absence of teeth. Missing one or more teeth is common, but absence of multiple teeth is rare. The present case report describes multiple missing permanent teeth in a non syndromic familial tooth agenesis patient and an overview of the genetic concepts involved in tooth agenesis. © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽
Keywords: Tooth agenesis Oligodontia Missing teeth Permanent teeth
1. Introduction Tooth agenesis is a developmental dental anomaly in humans. Hypodontia is the term used for congenital absence of deciduous or permanent teeth. Oligodontia means absence of at least six teeth, while anodontia refers to absence of all teeth. Tooth agenesis involves both the dentition with increased frequency seen in permanent dentition. This condition may appear as part of a recognized genetic syndrome or a non syndromic form. This paper presents a case report of non syndromic patient with multiple missing teeth along with an overview on basic genetic concepts involved in tooth agenesis. 2. Case report A 24 year old female patient reported with a chief complaint of mobility in lower front teeth for past 3 months. The past medical history was non contributory and family history revealed that she was born to non consanguineous marriage with normal delivery. Among the family members, patient’s brother and aunt have congenitally missing teeth. The pedigree chart was formulated for
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. Tel.: +91 9176311026. E-mail address: [email protected] (M. J).
the past two generations (Fig. 1). The patient had no history of systemic diseases, trauma and extractions. On general examination no abnormalities detected. On intra oral examination a total of 21 teeth were present. There were 13 retained deciduous teeth [55, 53, 63, 65, 71, 72, 73, 75, 81, 82, 83, 84, 85] and 8 permanent teeth [16, 14, 11, 21, 24, 36, 34, 46] (Fig. 2). Orthopantamograph (OPG) showed absence of permanent teeth in relation to the retained deciduous teeth (Fig. 3). The patient was unwilling to undergo genetic search due to financial difficulty. Based on clinical and radiographic examination, a diagnosis of non syndromic familial tooth agenesis was made. The line of treatment planned was fabrication of removable or fixed partial prosthesis with a multidisciplinary approach. 3. Discussion Tooth agenesis is a dental anomaly involving few specific teeth. The permanent dentition is commonly involved more than the deciduous with a prevalence of 1.6–9.6% [1]. Third molar is the most common tooth involved followed by maxillary lateral incisors. In most reports, the prevalence of dental agenesis in females was always higher than males as it was in our case [2]. The type of teeth reported missing varied in different ethnic groups. The mandibular second molar is the frequently missing tooth in Europeans, the maxillary lateral incisors in Asian subcontinent and the mandibular central or lateral incisors in the Chinese populations. Unilateral hypodontia is more common than bilateral [3]. Tooth agenesis is a feature of many syndromes that affect teeth along with several ectodermal derivatives like skin, hair, etc. The absence of maxillary central incisor, canine and molars is rare in
2212-5558/$ – see front matter © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽 http://dx.doi.org/10.1016/j.ajoms.2013.11.005
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005
G Model JOMSMP-243; No. of Pages 3 2
ARTICLE IN PRESS S.M.S. SS et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
Fig. 3. OPG demonstrating missing permanent teeth 12, 13, 15, 17, 18, 22, 23, 25, 26, 27, 28, 31, 32, 33, 35, 37, 38, 41, 42, 43, 44, 45, 47, 48.
Fig. 1. The pedigree chart.
hypodontia but seen frequently associated with severe syndromic forms. Down syndrome patients have a high prevalence rate of 63% of hypodontia involving incisors. The genetic background involved is in the trisomy of chromosome 21 [4]. Cleft lip and palate patients have missing maxillary lateral incisor in the cleft region because of MSX1 gene mutation [5]. Van der Woude syndrome is an autosomal dominant disorder affecting missing teeth, cleft lip, palate and lip pits. Studies have showed a mutation in the interferon regulatory factor 6 (IRF 6) in this syndrome [6]. Ectodermal dysplasia is characterized by defects in the ectodermal structures. Hypohidrotic ectodermal dysplasia is a congenital disorder of teeth, hair and sweat glands are caused by mutation in the ectodysplasin A [7].
Fig. 2. Intraoral photograph of maxillary arch showing 11, 53, 14, 55, 21, 63, 24, 65 and mandibular arch showing retained deciduous 71, 72, 73, 75, 81, 82, 83, 84 and 85.
Incontinentia pigmenti is a disorder involving skin as an X linked dominant pattern associated malformation of the hair, nail, eyes and teeth. It is caused by mutation in NEMO gene [8]. Rieger Syndrome is an autosomal dominant disorder involved the anterior segment of eye, periumblical skin, maxillary hypoplasia and hypodontia. Mutation of PITX2 gene has been identified in the condition [9]. In our case, the patient is ruled out of being associated with any syndrome and systemic conditions associated with missing teeth. Thus, congenital lack of permanent teeth without any systemic disorder or syndrome is suggestive of non syndromic familial tooth agenesis. Nonsyndromic or familial hypodontia is more common than the syndromic form. It follows an autosomal dominant, autosomal recessive or X linked pattern of inheritance with considerable variations in both penetrance and inheritance [10]. Recent advances in the field of molecular biology and human genetics give us a vision in understanding the genes involved in the tooth formation. Tooth formation is a specialized, highly co-ordinated complex process which is controlled by more than 100 genes. Many genes and transcription factors are involved like Homeobox gene, Hedgehog gene, Bone morphogenic proteins, fibroblast growth factor, etc. [11]. Homeobox genes are a set of genes that determine an organized pattern in vertebrates. It was first isolated in the fly Drosophila melanogaster [12]. The temporal and spatial controls of this gene expression are essential for correct pattering of teeth in many animals. In mammals 38 Hox genes have been identified in four main chromosomal clusters. They involve in induction, pattering, and epithelial mesenchymal interactions and programmed cell death in the craniofacial development [13]. MSX gene stands for muscle segment homeobox gene and has been reported by Campbell et al. to be homologous to mouse homeobox gene Hox-7 [14]. In humans, genetic linkage analysis of a family with autosomal dominant selective hypodontia demonstrates mutation in Msx gene localized to chromosome 4p16 [13]. MSX gene predominantly affects second premolar and third molar agenesis [15]. PAX9 gene is essential for development of skeletal elements and for the dental mesenchyme to condense around tooth bud epithelium. Pax9 is required for mesenchymal expression of Msx, Bmp4 and lef1 [16]. In humans, mutations of Pax9 are associated with unique phenotype of familial tooth agenesis that mainly involves posterior teeth. A single base insertion producing frame shift mutation in the paired domain of pax9 is identified in a family exhibiting lack of permanent molar. Affected member had normal primary dentition. Several mutation and polymorphism in promoter region of pax9 gene have been identified in association with a variable form of oligodontia [17]. Bar class homeobox Barx genes were isolated in Drosophila at chromosome 11q25. Barx is expressed in the ectomesenchyme
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005
G Model JOMSMP-243; No. of Pages 3
ARTICLE IN PRESS S.M.S. SS et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
of the first branchial arch and localized around developing molars. Mutation of the genes led to facial and dental anomalies [13]. Dlx (distal less homeobox gene) at 2q32 chromosome was reported by McGuiness et al. It is essential for migration of neural crest cells and located around where molar teeth will develop [13]. Axin 2–genetic linkage and mutational analysis of a Finnish family with autosomal dominant oligodontia has demonstrated mutation in Axin inhibitor protein 2. The studies showed polymorphism in Axin 2 may be the risk factor for selective tooth agenesis [18]. Bone morphogenic proteins are group of proteins play essential role in tissue interaction by transferring signals. Bmp 2, 4, 7 are involving in odontogenesis. Fibroblast growth factor is also involved in regulating the epithelial mesenchymal interaction [19]. FGF 4, 8, 9 are involved in odontogenesis [19]. Latent transforming growth factor beta binding protein modulates the bioavailability of TGF-beta. In studies mutation of these factors causes autosomal recessive form of familial oligodontia [20]. The X linked recessive type ectodysplasin (EDA) gene located at Xq12-q13.1. The gene mutation showed congenital absence of maxillary and mandibular central lateral incisors [21]. Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait and caused by mutation in the gene encoding ectodysplasin-A (EDA). In studies showed that EDA mutation can result in nonsyndromic tooth agenesis [22]. 4. Conclusion Hypodontia is seen more in familial teeth agenesis than in syndromic patients suggesting the influence of mutated genes as an etiology of tooth agenesis. X linked recessive type ectodysplasin is one of the genes associated with incisor teeth agenesis. MSX, PAX9, Dlx and Barx gene mutations have been reported in premolar and molar teeth agenesis. Axin 2 genes, BMP 2, 4, 7, FGF and TGF-alpha factors have been reported to be involved in familial hypodontia. Careful treatment planning and current understanding of the condition with the genetic background are important to prevent esthetic, functional and psychological problems. Hence multidisciplinary approach is needed. Conflict of interest None.
3
References [1] Vastardis H. The genetics of human tooth agenesis. New discoveries for understanding dental anomalies. Am J Orthod Dentofac Orthop 2000;117:650–6. [2] Altug-Atac AT, Erdem D. Prevalence and distribution of dental anomalies in orthodontic patients. Am J Orthod Dentofac Orthop 2007;131:510–4. [3] Shimizu T, Maeda T. Prevalence and genetic basis of tooth agenesis. Jpn Dent Sci Rev 2009;45:52–8. [4] Kumasaka S, Miyagi A, Sakai N, Shindo J, Kashima I. Oligodontia a radiographic comparison of subjects with Down syndrome and normal subjects. Spec Care Dentist 1997;17:137–41. [5] Jezewski PA, Vieira AR, Nishimura C, Ludwig B, Johnson M, O’Brien SE, et al. Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate. J Med Genet 2003;40:399–407. [6] Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 2002;32:285–9 [letter]. [7] Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B, et al. Xlinked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996;13:409–16. [8] Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel Xlinked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000;67:1555–62. [9] Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 1996;14:392–9. [10] Pirinen S, Kentala A, Nieminen P, Varilo T, Thesleff I, Arte S. Recessively inherited lower incisor hypodontia. J Med Genet 2001;38:551–6. [11] Nalin Kumar S, Ranganathan K, Umadevi M, Joshua E, Saraswathi TR, Krishnaswamy NR. Current genetic concepts of odontogenesis and tooth agenesis. J Ind Orthod Soc 2003;36:164–8. [12] McGnnis W, Krumlauf. Homeobox genes and axial patterning. Cell 1992;68:283–302. [13] Krishnan V. Genomics and orafacial clefts. J Ind Orthod Soc 2003;36:39–51. [14] Campbell K, Flavin N, Ivens A, Robert B, Buckingham M, Williamson R. The human homeobox gene HOX7 maps to 4p16.1 and is deleted in WolfHirschhorn syndrome patients. Am J Hum Genet 1989;45(suppl.):A179. [15] Kim JW, Simmer JP, Lin BP, Hu JC. Novel MSX1 frame shift causes autosomaldominant oligodontia. J Dent Res 2006;85:267–71. [16] Peters H, Neubuser A, Kratochwil K, Balling R. Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes Dev 1998;12:2735–47. [17] Klein ML, Nieminen P, Lammi L, Niebur E, Kreiborg S. Novel mutation of the initiation codon of PAX9 causes oligodontia. J Dent Res 2005;84:43–7. [18] Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I. mutations in AXIN 2 causes familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043–50. [19] Cobourne Mt. The genetic control of early odontogenesis. Br J Orthod 1999;26:21–5. [20] Noor A, Windpassinger C, Vitc I, Orlic M, Rafiq MA, Khalid M. Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein. Am J Hum Genet 2009;84:519–23. [21] Han D, Gong Y, Wu H, Zhang X, Yan M, Wang X. Novel EDA mutation resulting in X linked non syndromic hypodontia and the pattern of EDA associated isolated tooth agenesis. Eur J Med Genet 2008;51:536–46. [22] Nikopensius T, Annilo T, Jagomägi T, Gilissen C, Kals M, Krjutˇskov K. Non-syndromic tooth agenesis associated with a nonsense mutation in ectodysplasin-A (EDA). J Dent Res 2013;92:507–11.
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005
ARTICLE IN PRESS Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Non syndromic familial tooth agenesis—A case report and overview of genetic factors Shaik Mohamed Shamsudeen SS, Nalin Kumar S, Sujatha G, Muruganandhan J ∗ Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Off OMR, Thalambur, Chennai 603103, Tamil Nadu, India
a r t i c l e
i n f o
Article history: Received 24 September 2013 Received in revised form 12 November 2013 Accepted 20 November 2013 Available online xxx
a b s t r a c t Tooth agenesis is one of the most common anomalies of the human dentition characterized by the developmental absence of teeth. Missing one or more teeth is common, but absence of multiple teeth is rare. The present case report describes multiple missing permanent teeth in a non syndromic familial tooth agenesis patient and an overview of the genetic concepts involved in tooth agenesis. © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽
Keywords: Tooth agenesis Oligodontia Missing teeth Permanent teeth
1. Introduction Tooth agenesis is a developmental dental anomaly in humans. Hypodontia is the term used for congenital absence of deciduous or permanent teeth. Oligodontia means absence of at least six teeth, while anodontia refers to absence of all teeth. Tooth agenesis involves both the dentition with increased frequency seen in permanent dentition. This condition may appear as part of a recognized genetic syndrome or a non syndromic form. This paper presents a case report of non syndromic patient with multiple missing teeth along with an overview on basic genetic concepts involved in tooth agenesis. 2. Case report A 24 year old female patient reported with a chief complaint of mobility in lower front teeth for past 3 months. The past medical history was non contributory and family history revealed that she was born to non consanguineous marriage with normal delivery. Among the family members, patient’s brother and aunt have congenitally missing teeth. The pedigree chart was formulated for
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. Tel.: +91 9176311026. E-mail address: [email protected] (M. J).
the past two generations (Fig. 1). The patient had no history of systemic diseases, trauma and extractions. On general examination no abnormalities detected. On intra oral examination a total of 21 teeth were present. There were 13 retained deciduous teeth [55, 53, 63, 65, 71, 72, 73, 75, 81, 82, 83, 84, 85] and 8 permanent teeth [16, 14, 11, 21, 24, 36, 34, 46] (Fig. 2). Orthopantamograph (OPG) showed absence of permanent teeth in relation to the retained deciduous teeth (Fig. 3). The patient was unwilling to undergo genetic search due to financial difficulty. Based on clinical and radiographic examination, a diagnosis of non syndromic familial tooth agenesis was made. The line of treatment planned was fabrication of removable or fixed partial prosthesis with a multidisciplinary approach. 3. Discussion Tooth agenesis is a dental anomaly involving few specific teeth. The permanent dentition is commonly involved more than the deciduous with a prevalence of 1.6–9.6% [1]. Third molar is the most common tooth involved followed by maxillary lateral incisors. In most reports, the prevalence of dental agenesis in females was always higher than males as it was in our case [2]. The type of teeth reported missing varied in different ethnic groups. The mandibular second molar is the frequently missing tooth in Europeans, the maxillary lateral incisors in Asian subcontinent and the mandibular central or lateral incisors in the Chinese populations. Unilateral hypodontia is more common than bilateral [3]. Tooth agenesis is a feature of many syndromes that affect teeth along with several ectodermal derivatives like skin, hair, etc. The absence of maxillary central incisor, canine and molars is rare in
2212-5558/$ – see front matter © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽 http://dx.doi.org/10.1016/j.ajoms.2013.11.005
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005
G Model JOMSMP-243; No. of Pages 3 2
ARTICLE IN PRESS S.M.S. SS et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
Fig. 3. OPG demonstrating missing permanent teeth 12, 13, 15, 17, 18, 22, 23, 25, 26, 27, 28, 31, 32, 33, 35, 37, 38, 41, 42, 43, 44, 45, 47, 48.
Fig. 1. The pedigree chart.
hypodontia but seen frequently associated with severe syndromic forms. Down syndrome patients have a high prevalence rate of 63% of hypodontia involving incisors. The genetic background involved is in the trisomy of chromosome 21 [4]. Cleft lip and palate patients have missing maxillary lateral incisor in the cleft region because of MSX1 gene mutation [5]. Van der Woude syndrome is an autosomal dominant disorder affecting missing teeth, cleft lip, palate and lip pits. Studies have showed a mutation in the interferon regulatory factor 6 (IRF 6) in this syndrome [6]. Ectodermal dysplasia is characterized by defects in the ectodermal structures. Hypohidrotic ectodermal dysplasia is a congenital disorder of teeth, hair and sweat glands are caused by mutation in the ectodysplasin A [7].
Fig. 2. Intraoral photograph of maxillary arch showing 11, 53, 14, 55, 21, 63, 24, 65 and mandibular arch showing retained deciduous 71, 72, 73, 75, 81, 82, 83, 84 and 85.
Incontinentia pigmenti is a disorder involving skin as an X linked dominant pattern associated malformation of the hair, nail, eyes and teeth. It is caused by mutation in NEMO gene [8]. Rieger Syndrome is an autosomal dominant disorder involved the anterior segment of eye, periumblical skin, maxillary hypoplasia and hypodontia. Mutation of PITX2 gene has been identified in the condition [9]. In our case, the patient is ruled out of being associated with any syndrome and systemic conditions associated with missing teeth. Thus, congenital lack of permanent teeth without any systemic disorder or syndrome is suggestive of non syndromic familial tooth agenesis. Nonsyndromic or familial hypodontia is more common than the syndromic form. It follows an autosomal dominant, autosomal recessive or X linked pattern of inheritance with considerable variations in both penetrance and inheritance [10]. Recent advances in the field of molecular biology and human genetics give us a vision in understanding the genes involved in the tooth formation. Tooth formation is a specialized, highly co-ordinated complex process which is controlled by more than 100 genes. Many genes and transcription factors are involved like Homeobox gene, Hedgehog gene, Bone morphogenic proteins, fibroblast growth factor, etc. [11]. Homeobox genes are a set of genes that determine an organized pattern in vertebrates. It was first isolated in the fly Drosophila melanogaster [12]. The temporal and spatial controls of this gene expression are essential for correct pattering of teeth in many animals. In mammals 38 Hox genes have been identified in four main chromosomal clusters. They involve in induction, pattering, and epithelial mesenchymal interactions and programmed cell death in the craniofacial development [13]. MSX gene stands for muscle segment homeobox gene and has been reported by Campbell et al. to be homologous to mouse homeobox gene Hox-7 [14]. In humans, genetic linkage analysis of a family with autosomal dominant selective hypodontia demonstrates mutation in Msx gene localized to chromosome 4p16 [13]. MSX gene predominantly affects second premolar and third molar agenesis [15]. PAX9 gene is essential for development of skeletal elements and for the dental mesenchyme to condense around tooth bud epithelium. Pax9 is required for mesenchymal expression of Msx, Bmp4 and lef1 [16]. In humans, mutations of Pax9 are associated with unique phenotype of familial tooth agenesis that mainly involves posterior teeth. A single base insertion producing frame shift mutation in the paired domain of pax9 is identified in a family exhibiting lack of permanent molar. Affected member had normal primary dentition. Several mutation and polymorphism in promoter region of pax9 gene have been identified in association with a variable form of oligodontia [17]. Bar class homeobox Barx genes were isolated in Drosophila at chromosome 11q25. Barx is expressed in the ectomesenchyme
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005
G Model JOMSMP-243; No. of Pages 3
ARTICLE IN PRESS S.M.S. SS et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2014) xxx–xxx
of the first branchial arch and localized around developing molars. Mutation of the genes led to facial and dental anomalies [13]. Dlx (distal less homeobox gene) at 2q32 chromosome was reported by McGuiness et al. It is essential for migration of neural crest cells and located around where molar teeth will develop [13]. Axin 2–genetic linkage and mutational analysis of a Finnish family with autosomal dominant oligodontia has demonstrated mutation in Axin inhibitor protein 2. The studies showed polymorphism in Axin 2 may be the risk factor for selective tooth agenesis [18]. Bone morphogenic proteins are group of proteins play essential role in tissue interaction by transferring signals. Bmp 2, 4, 7 are involving in odontogenesis. Fibroblast growth factor is also involved in regulating the epithelial mesenchymal interaction [19]. FGF 4, 8, 9 are involved in odontogenesis [19]. Latent transforming growth factor beta binding protein modulates the bioavailability of TGF-beta. In studies mutation of these factors causes autosomal recessive form of familial oligodontia [20]. The X linked recessive type ectodysplasin (EDA) gene located at Xq12-q13.1. The gene mutation showed congenital absence of maxillary and mandibular central lateral incisors [21]. Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait and caused by mutation in the gene encoding ectodysplasin-A (EDA). In studies showed that EDA mutation can result in nonsyndromic tooth agenesis [22]. 4. Conclusion Hypodontia is seen more in familial teeth agenesis than in syndromic patients suggesting the influence of mutated genes as an etiology of tooth agenesis. X linked recessive type ectodysplasin is one of the genes associated with incisor teeth agenesis. MSX, PAX9, Dlx and Barx gene mutations have been reported in premolar and molar teeth agenesis. Axin 2 genes, BMP 2, 4, 7, FGF and TGF-alpha factors have been reported to be involved in familial hypodontia. Careful treatment planning and current understanding of the condition with the genetic background are important to prevent esthetic, functional and psychological problems. Hence multidisciplinary approach is needed. Conflict of interest None.
3
References [1] Vastardis H. The genetics of human tooth agenesis. New discoveries for understanding dental anomalies. Am J Orthod Dentofac Orthop 2000;117:650–6. [2] Altug-Atac AT, Erdem D. Prevalence and distribution of dental anomalies in orthodontic patients. Am J Orthod Dentofac Orthop 2007;131:510–4. [3] Shimizu T, Maeda T. Prevalence and genetic basis of tooth agenesis. Jpn Dent Sci Rev 2009;45:52–8. [4] Kumasaka S, Miyagi A, Sakai N, Shindo J, Kashima I. Oligodontia a radiographic comparison of subjects with Down syndrome and normal subjects. Spec Care Dentist 1997;17:137–41. [5] Jezewski PA, Vieira AR, Nishimura C, Ludwig B, Johnson M, O’Brien SE, et al. Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate. J Med Genet 2003;40:399–407. [6] Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 2002;32:285–9 [letter]. [7] Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B, et al. Xlinked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996;13:409–16. [8] Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel Xlinked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000;67:1555–62. [9] Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 1996;14:392–9. [10] Pirinen S, Kentala A, Nieminen P, Varilo T, Thesleff I, Arte S. Recessively inherited lower incisor hypodontia. J Med Genet 2001;38:551–6. [11] Nalin Kumar S, Ranganathan K, Umadevi M, Joshua E, Saraswathi TR, Krishnaswamy NR. Current genetic concepts of odontogenesis and tooth agenesis. J Ind Orthod Soc 2003;36:164–8. [12] McGnnis W, Krumlauf. Homeobox genes and axial patterning. Cell 1992;68:283–302. [13] Krishnan V. Genomics and orafacial clefts. J Ind Orthod Soc 2003;36:39–51. [14] Campbell K, Flavin N, Ivens A, Robert B, Buckingham M, Williamson R. The human homeobox gene HOX7 maps to 4p16.1 and is deleted in WolfHirschhorn syndrome patients. Am J Hum Genet 1989;45(suppl.):A179. [15] Kim JW, Simmer JP, Lin BP, Hu JC. Novel MSX1 frame shift causes autosomaldominant oligodontia. J Dent Res 2006;85:267–71. [16] Peters H, Neubuser A, Kratochwil K, Balling R. Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes Dev 1998;12:2735–47. [17] Klein ML, Nieminen P, Lammi L, Niebur E, Kreiborg S. Novel mutation of the initiation codon of PAX9 causes oligodontia. J Dent Res 2005;84:43–7. [18] Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I. mutations in AXIN 2 causes familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043–50. [19] Cobourne Mt. The genetic control of early odontogenesis. Br J Orthod 1999;26:21–5. [20] Noor A, Windpassinger C, Vitc I, Orlic M, Rafiq MA, Khalid M. Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein. Am J Hum Genet 2009;84:519–23. [21] Han D, Gong Y, Wu H, Zhang X, Yan M, Wang X. Novel EDA mutation resulting in X linked non syndromic hypodontia and the pattern of EDA associated isolated tooth agenesis. Eur J Med Genet 2008;51:536–46. [22] Nikopensius T, Annilo T, Jagomägi T, Gilissen C, Kals M, Krjutˇskov K. Non-syndromic tooth agenesis associated with a nonsense mutation in ectodysplasin-A (EDA). J Dent Res 2013;92:507–11.
Please cite this article in press as: SS SMS, et al. Non syndromic familial tooth agenesis—A case report and overview of genetic factors. J Oral Maxillofac Surg Med Pathol (2014), http://dx.doi.org/10.1016/j.ajoms.2013.11.005