RESUMEN
Amelogenesis, the intricate process governing enamel formation, is susceptible to a range of genetic, systemic, and environmental influences, resulting in distinct developmental defects of enamel (DDE), such as molar incisor hypomineralisation (MIH), enamel hypoplasia, dental fluorosis, and amelogenesis imperfecta (AI). This chapter aims to provide a comprehensive overview of amelogenesis and DDE, establishing correlations between histopathological findings and clinical manifestations. MIH, a qualitative enamel defect, occurs during the mineralisation and maturation phases, affecting first permanent molars and eventually incisors. Diagnostic challenges in MIH arise from the disorder's unique features, including variable tooth involvement and severity, influenced by a complex interplay of genetic, systemic, and environmental factors. Enamel hypoplasia, a quantitative defect, manifests in any tooth during enamel matrix secretion. Etiological factors include local, systemic, environmental, and genetic influences, with variable enamel matrix abnormalities depending on the stage of amelogenesis when aggression occurred. Dental fluorosis, a toxicological concern from chronic and excessive fluoride exposure, affects ameloblasts and compromises crystal growth of the homologous teeth during enamel development. Lastly, AI, an inherited condition, encompasses diverse phenotypes in enamel development. AI phenotypes, whether hypoplastic or hypomineralised, entail mutations in genes, such as AMELX, ENAM, MMP20, KLK4, WDR72, FAM83H, C4ORF26, amelotin, GPR68, and ACPT. Diagnosing AI involves considering family history and clinical observation. In conclusion, navigating the intricacies of amelogenesis, from MIH to AI, underscores the critical importance of accurate diagnosis for proper clinical management of DDE.
Asunto(s)
Amelogénesis Imperfecta , Amelogénesis , Hipoplasia del Esmalte Dental , Esmalte Dental , Fluorosis Dental , Humanos , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/diagnóstico , Amelogénesis Imperfecta/patología , Hipoplasia del Esmalte Dental/genética , Hipoplasia del Esmalte Dental/diagnóstico , Fluorosis Dental/etiología , Fluorosis Dental/patología , Amelogénesis/genética , Esmalte Dental/anomalías , Esmalte Dental/patología , Defectos del Desarrollo del EsmalteRESUMEN
Amelogenesis imperfecta (AI) is a genetic disease characterized by poor formation of tooth enamel. AI occurs due to mutations, especially in AMEL, ENAM, KLK4, MMP20, and FAM83H, associated with changes in matrix proteins, matrix proteases, cell-matrix adhesion proteins, and transport proteins of enamel. Due to the wide variety of phenotypes, the diagnosis of AI is complex, requiring a genetic test to characterize it better. Thus, there is a demand for developing low-cost, noninvasive, and accurate platforms for AI diagnostics. This case-control pilot study aimed to test salivary vibrational modes obtained in attenuated total reflection fourier-transformed infrared (ATR-FTIR) together with machine learning algorithms: linear discriminant analysis (LDA), random forest, and support vector machine (SVM) could be used to discriminate AI from control subjects due to changes in salivary components. The best-performing SVM algorithm discriminates AI better than matched-control subjects with a sensitivity of 100%, specificity of 79%, and accuracy of 88%. The five main vibrational modes with higher feature importance in the Shapley Additive Explanations (SHAP) were 1010 cm-1, 1013 cm-1, 1002 cm-1, 1004 cm-1, and 1011 cm-1 in these best-performing SVM algorithms, suggesting these vibrational modes as a pre-validated salivary infrared spectral area as a potential biomarker for AI screening. In summary, ATR-FTIR spectroscopy and machine learning algorithms can be used on saliva samples to discriminate AI and are further explored as a screening tool.
Asunto(s)
Amelogénesis Imperfecta , Aprendizaje Automático , Saliva , Humanos , Amelogénesis Imperfecta/diagnóstico , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/metabolismo , Saliva/metabolismo , Saliva/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Femenino , Estudios de Casos y Controles , Masculino , Algoritmos , Adulto , Máquina de Vectores de Soporte , Proyectos Piloto , Análisis Discriminante , Biomarcadores , Triaje/métodos , Adolescente , Adulto JovenRESUMEN
Importance: Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported. Objective: To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa. Design, Settings, and Participants: This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa. Main Outcomes and Measures: The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma. Results: The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients). Conclusions and Relevance: These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.
Asunto(s)
Epidermólisis Ampollosa , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Preescolar , Adolescente , Niño , Epidermólisis Ampollosa/complicaciones , Persona de Mediana Edad , Estudios Longitudinales , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/epidemiología , Carcinoma de Células Escamosas/patología , Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/patología , Estudios de Cohortes , Neoplasias de la Boca/patología , Neoplasias de la Boca/complicaciones , Gingivitis/patología , Gingivitis/etiología , Queilitis , ChileRESUMEN
Amelogenesis imperfecta (AI) is a group of rare genetic conditions characterized by quantitative and/or qualitative tooth enamel alterations. AI can manifest as an isolated trait or as part of a syndrome. Recently, five biallelic disease-causing variants in the RELT gene were identified in 7 families with autosomal recessive amelogenesis imperfecta (ARAI). RELT encodes an orphan receptor in the tumor necrosis factor (TNFR) superfamily expressed during tooth development, with unknown function. Here, we report one Brazilian and two French families with ARAI and a distinctive hypomineralized phenotype with hypoplastic enamel, post-eruptive enamel loss, and occlusal attrition. Using Next Generation Sequencing (NGS), four novel RELT variants were identified (c.120+1G>A, p.(?); c.120+1G>T, p.(?); c.193T>C, p.(Cys65Arg) and c.1260_1263dup, p.(Arg422Glyfs*5)). Our findings extend the knowledge of ARAI dental phenotypes and expand the disease-causing variants spectrum of the RELT gene.
Asunto(s)
Amelogénesis Imperfecta , Humanos , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/patología , Receptores del Factor de Necrosis Tumoral/genética , Fenotipo , Brasil , LinajeRESUMEN
In recent years, a rare form of autosomal recessive brachyolmia associated with amelogenesis imperfecta (AI) has been described as a novel nosologic entity. This disorder is characterized by skeletal dysplasia (e.g., platyspondyly, short trunk, scoliosis, broad ilia, elongated femoral necks with coxa valga) and severe enamel and dental anomalies. Pathogenic variants in the latent transforming growth factor-ß binding protein 3 (LTBP3) gene have been found implicated in the pathogenesis of this disorder. So far, biallelic pathogenic LTBP3 variants have been identified in less than 10 families. We here report a young boy born from consanguineous parents with a complex phenotype including skeletal dysplasia associated with aortic stenosis, hypertrophic cardiomyopathy, hypodontia and amelogenesis imperfecta caused by a previously unreported homozygous LTBP3 splice site variant. We also compare the genotypes and phenotypes of patients reported to date. This work provides further evidence that brachyolmia with amelogenesis imperfecta is a distinct nosologic entity and that variations in LTBP3 are involved in its pathogenesis.
Asunto(s)
Amelogénesis Imperfecta/genética , Proteínas de Unión a TGF-beta Latente/genética , Osteocondrodisplasias/genética , Adolescente , Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/diagnóstico , Consanguinidad , Humanos , Masculino , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/diagnóstico , Linaje , Perú , Fenotipo , Enfermedades Raras , Secuenciación del ExomaAsunto(s)
Amelogénesis Imperfecta/diagnóstico , Demencia/diagnóstico , Epilepsia Generalizada/genética , Epilepsia/diagnóstico , Anomalías Dentarias/genética , Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/genética , Demencia/complicaciones , Demencia/genética , Epilepsia/complicaciones , Epilepsia/genética , Femenino , Humanos , Mutación , Simportadores/genética , Adulto JovenRESUMEN
Resumen La amelogenesis imperfecta (AI) es un trastorno hereditario que afecta la estructura y apariencia clínica del esmalte dental. Hasta la fecha, se han asociado las mutaciones de 18 genes como la etiología de la AI no sindrómica. El objetivo de este trabajo es actualizar los conocimientos vigentes acerca de los genes ENAM, AMBN, FAM83H, MMP20 y KLK4 causantes de los diferentes tipos de AI. Metodología: Se realizó una búsqueda bibliográfica considerando artículos científicos desde el 2003 al 2021 sobre mutaciones en los genes mencionados en los siguientes portales: scielo, Pubmed/MEDLINE, Cochrane y Springer Link. Resultados: 37 artículos cumplieron los criterios de inclusión y fueron utilizados para esta revisión. Conclusiones: Dependiendo del gen implicado, las alteraciones del esmalte pueden mostrar una variedad de características. Los mecanismos biológicos que conducen a la enfermedad son múltiples y variados, sin embargo, muchos de ellos no están del todo claro aún, por lo que se requerirá de más investigaciones para mejorar nuestra comprensión del tema.
Amelogenesis imperfecta (AI) is an inherited disorder that affects the structure and clinical appearance of tooth enamel. Mutations of 18 genes have been associated as the etiology of AI. The objective of this work is to update the current knowledge about ENAM, AMBN, FAM83H, MMP20 and KLK4 genes that cause the different types of AI. Methodology: A bibliographic search was carried out considering scientific articles from 2003 to 2021 with regard to specific mutations in the aforementioned genes in the following portals: scielo, Pubmed / MEDLINE, Cochrane and Springer Link. Results: 37 articles met the inclusion criteria and were used for the development of this review. Conclusions: Depending on the gene involved, enamel alterations can show a variety of characteristics. The biological mechanisms that lead to the disease are multiple and varied, however many of them are not entirely clear yet, so more research will be required to improve our understanding of the subject.
A amelogênese imperfeita (AI) é uma doença hereditária que afeta a estrutura e aparência clínica do esmalte dentário. Mutações de 18 genes têm sido associadas como causa do AI. O objetivo deste trabalho é atualizar o conhecimento atual sobre genes ENAM, AMBN, FAM83H, MMP20 e KLK4 que causam os diferentes tipos de IA. Metodologia: Foi realizada uma busca bibliográfica considerando artigos científicos de 2003 até 2021 sobre mutações específicas nos genes citados nos seguintes portais: scielo, Pubmed / MEDLINE, Cochrane e Springer Link. Resultados: 37 artigos atenderam aos critérios de inclusão e foram utilizados para o desenvolvimento desta revisão. Conclusões: Dependendo do gene envolvido, as alterações do esmalte podem apresentar uma variedade de características. Os mecanismos biológicos que levam à doença são múltiplos e variados, porém muitos de les ainda não estão totalmente esclarecidos, portanto, mais pesquisas serão necessárias para melhorar nossa compreensão do assunto.
Asunto(s)
Amelogénesis Imperfecta/genética , Esmalte Dental , MutaciónRESUMEN
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disease caused by mutations in the CLDN16 or CLDN19 gene; however, few cases develop classical amelogenesis imperfecta. Herein, we report the case of a boy with early clinical renal manifestations that started at 1 year of age and presenting with dental hypoplasia and growth delay. The patient presented with vomiting, polyuria, and polydipsia. Apart from recurrent sterile leukocyturia, erroneously treated as infectious, he was normal, except for short stature and amelogenesis imperfecta with gradually discolored teeth. Laboratory tests revealed hyperparathyroidism, hypomagnesemia, severe hypercalciuria, and hypermagnesuria on 24-h urine testing. Helical computed tomography confirmed nephrocalcinosis. We performed whole-exome sequencing (WES) to test the hypothesis of FHHNC and oligogenic inheritance of amelogenesis. Analysis of the WES binary sequence alignment/map file revealed the presence of exon 1 of the CLDN16 and absence of the other exons [c.325_c918*? (E2_E5del)]. We confirmed a CLDN16 E2_E5 homozygous deletion by multiplex ligation-dependent probe amplification and polymerase chain reaction assays. Although most mutations causing FHHNC are missense and nonsense mutations in the CLDN16 or CLDN19 gene, large deletions occur and may be misled by WES, which is generally used for genetic screening of oligogenic disorders. The patient received cholecalciferol, magnesium oxide and potassium citrate. Later, the combination with hydrochlorothiazide plus amiloride was prescribed, with a good response during follow-up. Our report broadens the phenotype of FHHNC, including severe early-onset amelogenesis and short stature, and reinforces the phenotype-genotype correlation of the large deletion found in CLDN16.
Asunto(s)
Amelogénesis Imperfecta , Claudinas/genética , Hipercalciuria/genética , Nefrocalcinosis/genética , Defectos Congénitos del Transporte Tubular Renal/genética , Amelogénesis Imperfecta/genética , Estatura , Niño , Homocigoto , Humanos , Masculino , Eliminación de SecuenciaRESUMEN
Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. OBJECTIVE: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. MATERIAL AND METHODS: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. RESULTS: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. CONCLUSION: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.
Asunto(s)
Amelogénesis Imperfecta/diagnóstico por imagen , Amelogénesis Imperfecta/genética , Genealogía y Heráldica , Patrón de Herencia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amelogénesis Imperfecta/epidemiología , Amelogénesis Imperfecta/patología , Niño , Preescolar , Chile/epidemiología , Esmalte Dental/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Distribución por Sexo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
This chapter describes methods related to the diagnosis of genetic dental diseases. Based on the present knowledge, clinical phenotyping and next-generation sequencing techniques are discussed. Methods necessary for Sanger sequencing, multiplex ligation-dependent probe amplification, and epigenetic modification methods are detailed. In addition, protocols for cell culture establishment and characterization from patients with inherited dental anomalies are described.
Asunto(s)
Epigénesis Genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Enfermedades Raras/genética , Enfermedades Dentales/genética , Amelogénesis Imperfecta/genética , Técnicas de Cultivo de Célula/métodos , ADN/genética , ADN/aislamiento & purificación , Humanos , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Anomalías Dentarias/genéticaRESUMEN
Amelogenesis imperfecta is a group of developmental disorders of the dental enamel that is mainly associated with mutations in the AMELX gene. Clinically, it presents different phenotypes that affect the structure and function of dental enamel both in primary and secondary dentition. The purpose of this study was to conduct a literature review on the AMELX functions and mutations that are related to amelogenesis imperfecta. A literature search was carried out in two databases: PubMed and Web of Science, using the keywords "AMELX", "amelogenin", "amelogenesis imperfecta" and "AMELX mutation". Forty articles were reviewed, with AMELX being found to be the predominant gene in the development of dental enamel and amelogenesis imperfecta by altering the structure of amelogenin. In the past few years, the characteristics of the amelogenesis imperfecta process have been described with different phenotypes of hypoplastic or hypo-mineralized enamel, and different mutations have been reported, by means of which the gene sequencing and the position of mutations have been determined.
La amelogénesis imperfecta es un grupo de trastornos de desarrollo del esmalte dental asociados principalmente con mutaciones en el gen AMELX. Clínicamente presenta diferentes fenotipos que afectan la estructura y función del esmalte, tanto de la dentición primaria como secundaria. El objetivo de este estudio fue realizar una revisión bibliográfica de las funciones y mutaciones de AMELX relacionadas con amelogénesis imperfecta. Se llevó a cabo una revisión bibliográfica en dos bases de datos: PubMed y Web of Science, usando las palabras clave "AMELX", "amelogenina", "amelogénesis imperfecta" y "mutación de AMELX". Fueron revisados 40 artículos y se encontró que AMELX es el gen predominante en el desarrollo del esmalte dental y de la amelogénesis imperfecta, alterando la estructura de la amelogenina. En los últimos años se han descrito las características en el proceso de amelogénesis imperfecta con diferentes fenotipos de esmalte hipoplásico o hipomineralizado y se han reportado diferentes mutaciones, con lo que se ha determinado la secuenciación del gen y las posiciones de las mutaciones.
Asunto(s)
Amelogénesis Imperfecta/genética , Amelogenina/genética , Esmalte Dental/patología , Amelogénesis Imperfecta/patología , Humanos , Mutación , FenotipoRESUMEN
Resumen La amelogénesis imperfecta es un grupo de trastornos de desarrollo del esmalte dental asociados principalmente con mutaciones en el gen AMELX. Clínicamente presenta diferentes fenotipos que afectan la estructura y función del esmalte, tanto de la dentición primaria como secundaria. El objetivo de este estudio fue realizar una revisión bibliográfica de las funciones y mutaciones de AMELX relacionadas con amelogénesis imperfecta. Se llevó a cabo una revisión bibliográfica en dos bases de datos: PubMed y Web of Science, usando las palabras clave AMELX, amelogenina, amelogénesis imperfecta y mutación de AMELX. Fueron revisados 40 artículos y se encontró que AMELX es el gen predominante en el desarrollo del esmalte dental y de la amelogénesis imperfecta, alterando la estructura de la amelogenina. En los últimos años se han descrito las características en el proceso de amelogénesis imperfecta con diferentes fenotipos de esmalte hipoplásico o hipomineralizado y se han reportado diferentes mutaciones, con lo que se ha determinado la secuenciación del gen y las posiciones de las mutaciones.
Abstract Amelogenesis imperfecta is a group of developmental disorders of the dental enamel that is mainly associated with mutations in the AMELX gene. Clinically, it presents different phenotypes that affect the structure and function of dental enamel both in primary and secondary dentition. The purpose of this study was to conduct a literature review on the AMELX functions and mutations that are related to amelogenesis imperfecta. A literature search was carried out in two databases: PubMed and Web of Science, using the keywords AMELX, amelogenin, amelogenesis imperfecta and AMELX mutation. Forty articles were reviewed, with AMELX being found to be the predominant gene in the development of dental enamel and amelogenesis imperfecta by altering the structure of amelogenin. In the past few years, the characteristics of the amelogenesis imperfecta process have been described with different phenotypes of hypoplastic or hypo-mineralized enamel, and different mutations have been reported, by means of which the gene sequencing and the position of mutations have been determined.
Asunto(s)
Humanos , Esmalte Dental/patología , Amelogenina/genética , Amelogénesis Imperfecta/genética , Fenotipo , Amelogénesis Imperfecta/patología , MutaciónRESUMEN
Enamel renal syndrome (ERS) is a rare autosomal recessive disorder not fully characterized. Here we investigated ERS characteristics in 11 patients from 5 Brazilian families through clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing. The patients' age ranged from 6 to 25 years-old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium). Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutation in FAM20A gene, characterized by one base pair deletion in exon 11, resulting in a frameshift replacing a glutamine at codon 483 for a lysine and terminating at position 24 [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], was detected in all patients, strongly suggesting a founder effect. Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Early diagnosis is essential to minimize the deleterious effects related to ERS. Here we report the largest series of patients with ERS in a same population, and describe, for the first time, a founder mutation for FAM20A.
Asunto(s)
Amelogénesis Imperfecta/genética , Proteínas del Esmalte Dental/genética , Genética de Población , Nefrocalcinosis/genética , Adolescente , Adulto , Amelogénesis Imperfecta/epidemiología , Amelogénesis Imperfecta/patología , Brasil/epidemiología , Niño , Exones/genética , Femenino , Efecto Fundador , Mutación del Sistema de Lectura/genética , Homocigoto , Humanos , Riñón/metabolismo , Riñón/patología , Masculino , Nefrocalcinosis/epidemiología , Nefrocalcinosis/patología , Linaje , Eliminación de Secuencia/genética , Adulto JovenRESUMEN
Abstract Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. Objective: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. Material and Methods: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. Results: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. Conclusion: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Patrón de Herencia , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/diagnóstico por imagen , Genealogía y Heráldica , Fenotipo , Chile/epidemiología , Distribución por Sexo , Estadísticas no Paramétricas , Esmalte Dental/patología , Amelogénesis Imperfecta/patología , Amelogénesis Imperfecta/epidemiología , Persona de Mediana EdadRESUMEN
Jalili syndrome (JS) is an autosomal recessive disease characterized by a combination of cone-rode retinal dytrophy (CRD) and amelogenesis imperfect (AI). Mutations in cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene cause JS. Here we described 2 families (3 members) affected by JS. In the first family, JS was caused by the homozygous p.Leu324Pro (c.971T > C) missense mutation and the affected patient developed both CRD and AI. In the second family, a specific combination of a compound heterozygous mutation was found - the p.Leu324Pro (c.971T > C) missense transition and the novel p.Tyr581* (c.1743C > G) nonsense mutation. The proband showed CRD and AI, but her father just developed eye alterations. Together, these findings suggest that the p.Leu324Pro mutation in homozygosis induces a complete phenotype with both CRD and AI, but in heterozygosis and in composition with the novel p.Tyr581* nonsense mutation in CNNM4 promotes variable clinical expressivity, particularly with lack of dental phenotypes. These different phenotypes could be explained by deletions affecting the proband's homologous allele, epistasia or interactions with environmental factors leading to residual activity of protein.
Asunto(s)
Amelogénesis Imperfecta/genética , Proteínas de Transporte de Catión/genética , Retinitis Pigmentosa/genética , Adolescente , Niño , Codón sin Sentido , Distrofias de Conos y Bastones , Femenino , HumanosRESUMEN
OBJECTIVE: Amelogenesis imperfecta (AI) is a group of clinically and genetically heterogeneous inherited conditions, causing alterations in the structure of enamel and chemical composition of enamel matrix during development. The objective of this study was to compare the clinical, radiographic, histological and immunohistochemical phenotypes of subjects affected with hypocalcified AI from three Chilean families and identify causal mutations in the FAM83H gene. DESIGN: The diagnosis was made using clinical, radiographic, histological and genealogical data from the patients, who were evaluated according to the classification criteria by Witkop. PCR and Sanger sequencing of the complete coding sequence and surrounding intron regions of the FAM83H gene were conducted. The structural study of the affected teeth was performed with light microscopy, scanning electron microscopy and immunohistochemistry. RESULTS: The probands of the three families were diagnosed with hypocalcified AI, but in only one of them the missense variant p.Gly557Cys was identified. This variant was not present in the SNP database or in 100 healthy controls and segregated with the disease in the affected family. Using light microscopy, a normal prismatic structure was observed in all three cases. However, the ultrastructure was found to be affected in two of the cases, showing persistence of organic matter including amelogenins. CONCLUSIONS: These results suggest that FAM83H missense mutation reported in one of the families analyzed in this study might cause a phenotype of hypocalcified enamel more attenuated with retention of amelogenin.
Asunto(s)
Amelogénesis Imperfecta/genética , Amelogenina/genética , Mutación Missense/genética , Proteínas/genética , Chile , Exones , Femenino , Humanos , Inmunohistoquímica , Masculino , Microscopía Electrónica de Rastreo , Linaje , FenotipoRESUMEN
OBJECTIVE: The purpose of this study was to conduct a multidisciplinary analysis of a specific type of tooth enamel disturbance (amelogenesis imperfecta) affecting two Chilean families to obtain a precise diagnosis and to investigate possible underlying mutations. MATERIALS AND METHODS: Two non-related families affected with amelogenesis imperfecta were evaluated with clinical, radiographic and histopathological methods. Furthermore, pedigrees of both families were constructed and the presence of eight mutations in the enamelin gene (ENAM) and three mutations in the enamelysin gene (MMP-20) were investigated by PCR and direct sequencing. RESULTS: In the two affected patients, the dental malformation presented as soft and easily disintegrated enamel and exposed dark dentin. Neither of the affected individuals presented with a dental and skeletal open bite. Histologically, a high level of an organic matrix with prismatic organization was found. Genetic analysis indicated that the condition is autosomal recessive in one family and either autosomal recessive or due to a new mutation in the other family. Molecular mutational analysis revealed that none of the eight mutations previously described in the ENAM gene or the three mutations in the MMP-20 gene were present in the probands. CONCLUSION: A multidisciplinary analysis allowed for a diagnosis of hypocalcified amelogenesis imperfecta, Witkop type III, which was unrelated to previously described mutations in the ENAM or MMP-20 genes.
Asunto(s)
Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/patología , Proteínas del Esmalte Dental/genética , Metaloproteinasa 20 de la Matriz/genética , Adolescente , Amelogénesis Imperfecta/clasificación , Estudios de Casos y Controles , Cefalometría , Niño , Análisis Mutacional de ADN , Femenino , Genes Recesivos , Humanos , Masculino , Mutación , Grupo de Atención al Paciente , LinajeRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the dentomaxillofacial imaging features of one family affected by the gingival fibromatosis (GF) and dental abnormalities (DA) syndrome. METHODS: Conventional radiographs (periapical and panoramic) and cone beam CT (CBCT) were performed in nine members of this family: four were affected by the syndrome and five were not. RESULTS: The four affected members demonstrated mild generalized GF in association with DA, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay on tooth eruption and pericoronal radiolucencies in unerupted teeth. None of these oral changes were identified in the five unaffected members. All nine members presented alterations in the paranasal sinuses and mucosal thickening of the maxillary sinus was the most common finding. CONCLUSION: Family members not affected by the syndrome showed similar alterations in the paranasal sinuses and CBCT was useful to characterize the dentomaxillofacial features of this new syndrome associating GF and DA.
Asunto(s)
Fibromatosis Gingival/diagnóstico por imagen , Adolescente , Adulto , Amelogénesis Imperfecta/diagnóstico por imagen , Amelogénesis Imperfecta/genética , Tomografía Computarizada de Haz Cónico , Consanguinidad , Calcificaciones de la Pulpa Dental/diagnóstico por imagen , Calcificaciones de la Pulpa Dental/genética , Femenino , Fibromatosis Gingival/genética , Genes Recesivos , Humanos , Masculino , Persona de Mediana Edad , Senos Paranasales/diagnóstico por imagen , Linaje , Radiografía Dental/métodos , Síndrome , Diente no Erupcionado/diagnóstico por imagen , Diente no Erupcionado/genética , Adulto JovenRESUMEN
Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.
Asunto(s)
Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/metabolismo , Bicarbonatos/metabolismo , Esmalte Dental/metabolismo , Simportadores de Sodio-Bicarbonato , Ameloblastos/metabolismo , Amelogénesis/genética , Amelogénesis Imperfecta/clasificación , Amelogénesis Imperfecta/fisiopatología , Animales , Esmalte Dental/fisiopatología , Estudios de Asociación Genética , Heterogeneidad Genética , Humanos , Concentración de Iones de Hidrógeno , Transporte Iónico/genética , Ratones , Mutación/genética , Ratas , Simportadores de Sodio-Bicarbonato/genética , Simportadores de Sodio-Bicarbonato/metabolismo , Diente/metabolismo , Diente/fisiopatologíaRESUMEN
AIM: The purpose of the case report was to describe the treatment of a 4(1/2)-year-old boy with amelogenesis imperfect (AI) in the primary dentition. BACKGROUND: AI is a hereditary condition that affects the development of enamel, causing quantity, structural, and compositional anomalies involving all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. CASE REPORT: A 4(1/2)-year-old boy was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of amelogenesis imperfecta. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms of both maxillary and mandibular primary incisors and canines. Improvements in the patient's psychological behavior and the elimination of tooth sensitiveness were observed, and the reestablishment of a normal occlusion resulted in improved eating habits. The child was monitored in the Pediatric Dentistry Clinic at four-month intervals until the mixed dentition stage. SUMMARY: The oral rehabilitation of young children with AI is necessary to reestablish the stomatognathic system function, so important for a child's systemic health. An adequate medical history and a careful clinical examination were essential for a correct diagnosis. Treatment was rendered that was appropriate for the child's age and clinical/psychological characteristics. CLINICAL SIGNIFICANCE: Cost-effective restorative techniques involving stainless steel and composite-resin crowns are shown for the restoration of a young patient with amelogensis imperfecta.