A multidisciplinary approach for the diagnosis of hypocalcified amelogenesis imperfecta in two Chilean families.

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.

Oral rehabilitation of a patient with amelogenesis imperfecta using removable overlay denture: a clinical report.

AIM: The aim of this study was oral rehabilitation of 17-year old patient with amelogenesis imperfecta using removable overlay denture in order to satisfy her esthetic and functional expectations and enhance her self-image. BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic disorders that primarily affect the quality and quantity of amelogenesis in both primary and permanent dentitions. The main clinical characteristics are severe attrition, tooth sensitivity and unesthetic appearance. CASE REPORT: This clinical report illustrates the oral rehabilitation of a 17-year-old girl with hypoplastic-hypomature type of AI with cobalt-chromium (Co-Cr) overlay removable partial denture (ORPD) that is one of the most economical and biocompatible replacements for noble metal and nickel-chromium (Ni-Cr) alloy. CONCLUSION: The presented case report suggests that Co-Cr ORPD can be a good temporary or even permanent treatment option for AI patients with limited budget, low esthetic concerns or medical limitations. CLINICAL SIGNIFICANCE: There are major advantages in cast metal ORPDs; they are simpler, less traumatic and less expensive than fixed prosthetic options. This case report supports their use in patients with amelogenesis imperfecta.

Prosthodontic management of patients with amelogenesis imperfecta.

INTRODUCTION: Amelogenesis Imperfecta (AI) is an heterogenous genetic disorder that disturbs the developing enamel structure. This rare ectodermal defect leads to a variety of clinical manifestations due to agenesis, hypoplasia, and/or hypomineralisation of the enamel. AIMS AND OBJECTIVES: To describe the prosthodontic management of dental anomalies commonly associated with AI. METHODS: By using the classification of Witkop and Rao (1971), the variation in clinical presentation of the different Types of AI are illustrated and discussed, in particular Type I AI and Type 4 AI. RESULTS AND CONCLUSIONS: Early diagnosis and prosthodontic management as part of a multidisciplinary, patient-centred approach are key factors to treatment success. Treatment options to address the oral complications are influenced by modifying factors including age, socioeconomic status, type and severity of the disorder, and intraoral status at the time of treatment planning. Ultimately, management includes pain and infection control, provision of aesthetics and restoration of function which may lead to patient satisfaction, psychological well-being and an improved quality of life.

Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

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.

Adhesive techniques and machineable high-performance polymer restorations for amelogenesis imperfecta in mixed dentition.

Amelogenesis imperfecta refers to a hereditary dysplasia of the enamel. As a result of various defects, qualitatively and/ or quantitatively abnormal enamel forms, while the dental structure remains normal. The following article describes the condition and presents the case of an 8-year-old boy who was dentally reconstructed both functionally and aesthetically using the adhesive technique and machinable high performance polymer restorations.

Hypocalcified type of amelogenesis imperfecta in a large family: clinical, radiographic, and histological findings, associated dento-facial anomalies, and resulting treatment load.

OBJECTIVE: The purpose of this study was to report on the clinical, radiographic, and histological dental findings and the resulting treatment load in a five-generation family with amelogenesis imperfecta (AI). MATERIAL AND METHODS: Thirteen affected and 15 unaffected individuals were examined clinically and radiographically. In addition, four exfoliated deciduous teeth were examined by scanning electron microscopy and microradiography. RESULTS: The mode of inheritance of AI was autosomal-dominant. At eruption, most of the tooth enamel was yellow, lacking translucency, and prone to gradual loss in subjects with AI. Post-eruptive breakdown of enamel was extensive in accordance with the histological observations of hypomineralized and porous enamel. Extensive enamel loss and discoloration were observed in older affected individuals. The treatment need had been extensive: 76.2% of the total number of teeth present in affected individuals had been treated with partial or full coverage compared to 1.7% of the teeth in unaffected relatives. Unaffected individuals had more endodontically treated teeth than AI-affected relatives. Adjunctive findings, e.g. tooth agenesis, tooth impaction, pulp stones, enlarged follicular space, and taurodontism, were rare in both groups. CONCLUSIONS: Affected family members had the hypocalcified type of AI, which is characterized by severe hypomineralization, extensive post-eruptive loss, and discoloration of the enamel. Adjunctive findings were rare. Individuals with the hypocalcified type of AI have an extensive restorative treatment load compared to unaffected relatives.

Phenotype and Variant Spectrum in the LAMB3 Form of Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders characterized by abnormal formation of dental enamel, either in isolation or as part of a syndrome. Heterozygous variants in laminin subunit beta 3 ( LAMB3) cause AI with dominant inheritance in the absence of other cosegregating clinical features. In contrast, biallelic loss-of-function variants in LAMB3 cause recessive junctional epidermolysis bullosa, characterized by life-threatening skin fragility. We identified 2 families segregating autosomal dominant AI with variable degrees of a distinctive hypoplastic phenotype due to pathogenic variants in LAMB3. Whole exome sequencing revealed a nonsense variant (c.3340G>T, p.E1114*) within the final exon in family 1, while Sanger sequencing in family 2 revealed a variant (c.3383-1G>A) in the canonical splice acceptor site of the final exon. Analysis of cDNA from family 2 revealed retention of the final intron leading to a premature termination codon. Two unerupted third molar teeth from individual IV:5 in family 2 were subject to computerized tomography and scanning electron microscopy. LAMB3 molar teeth have a multitude of cusps versus matched controls. LAMB3 enamel was well mineralized but pitted. The architecture of the initially secreted enamel was abnormal, with cervical enamel appearing much less severely affected than coronal enamel. This study further defines the variations in phenotype-genotype correlation for AI due to variants in LAMB3, underlines the clustering of nonsense and frameshift variants causing AI in the absence of junctional epidermolysis bullosa, and highlights the shared AI phenotype arising from variants in genes coding for hemidesmosome proteins.

Clinical diagnosis and oral rehabilitation of a patient with amelogenesis imperfecta: a case report.

AIM: This clinical report describes the oral rehabilitation of a young female patient diagnosed with the hypocalcified, autosomal recessive type of Amelogenesis imperfecta (AI). A brief discussion on diagnosis of AI is also included. BACKGROUND: AI has been defined as a group of hereditary enamel defects not associated with evidence of systemic disease. It can be characterized by enamel hypoplasia and/or hypomaturation or hypocalcification of the existing teeth. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation and the protection of these teeth. REPORT: A 31-year-old female patient presented with concerns including extreme sensitivity; dissatisfaction with size, shape, and shade of teeth; and poor masticatory efficiency. She was very conscious about the appearance of her teeth and reported that her primary dentition was affected in the same manner. The specific objectives of this treatment were to eliminate tooth sensitivity, enhance esthetics, and restore masticatory function. Treatment included crown lengthening procedures and placement of anterior and posterior metal-ceramic crowns. A 12-month follow-up with clinical and radiographic examinations revealed no evidence of any untoward effects of the treatment on the restored teeth or their supporting structures. SUMMARY: Management of a patient with AI is a challenge for the clinician. The treatment options vary considerably depending on several factors such as the age of the patient, socio-economic status, periodontal condition, loss of tooth structure, severity of the disorder, and, most importantly, the patient's cooperation. The clinician has to consider the long-term prognosis of the treatment outcome. This clinical report describes the fabrication of metal ceramic and all metal crowns for the restoration of severely worn teeth in a patient with AI which requires meticulous maintenance of oral hygiene and patient co-operation.

Enfoque de Tratamiento de una Adolescente con Amelogénesis Imperfecta / Treatment Approach for an Adolescent with Amelogenesis Imperfecta

La amelogénesis imperfecta (AI) es un grupo de tras-tornos hereditarios, clínica y etiológicamente hete-rogéneos, derivados de mutaciones genéticas, que se caracterizan por anomalías cualitativas y cuanti-tativas del desarrollo del esmalte, pudiendo afectar la dentición primaria y/o permanente. El tratamiento del paciente con AI es complejo y multidiscliplinario; supone un desafío para el odontólogo, ya que por lo general están involucradas todas las piezas dentarias y afecta no solo la salud buco dental sino el aspecto emocional y psicológico de los pacientes. Con el obje-tivo de describir el tratamiento integral y rehabilita-dor realizado en una paciente con diagnóstico de AI tipo III, se reporta el caso de un adolescente de sexo femenino de 13 años, que concurrió en demanda de atención a la Cátedra de Odontología Integral Niños de la Facultad de Odontología de la Universidad de Buenos Aires (FOUBA), cuyo motivo de consulta fue la apariencia estética y la hipersensibilidad de sus pie-zas dentarias. Durante el examen clínico intraoral, se observó que todas las piezas dentarias presentaban un esmalte rugoso, blando, con irregularidades y una coloración amarronada, compatible con diagnóstico de Amelogénesis Imperfecta tipo III hipomineralizada. Conclusión: El tratamiento rehabilitador de la AI en los pacientes en crecimiento y desarrollo estará diri-gido a intervenir de manera integral y temprana para resolver la apariencia estética y funcional, evitar las repercusiones sociales y emocionales, y acompañar a los pacientes y sus familias (AU)

Amelogenesis imperfecta (AI) is a group of clinically and etiologically heterogeneous hereditary disorders, derived from genetic mutations, characterized by qualitative and quantitative anomalies of enamel development, which can affect primary and/or permanent dentition. The treatment of patients with AI is complex and multidisciplinary, it is a challenge for the dentist, since in general all the teeth are involved and it affects not only oral health but also the emotional and psychological aspect of the patients. Objective: To describe the comprehensive and rehabilitative treatment carried out in an adolescent patient with a diagnosis of type III AI. Case report: The case of a 13-year-old female patient, who required dental attention at the Department of Dentistry for Children of the School of Dentistry of the University of Buenos Aires, whose reason for consultation was esthetic appearance and hypersensitivity of her teeth. In the intraoral clinical examination, it was observed that all the teeth had rough, soft enamel, with irregularities and a brownish color, compatible with the diagnosis of type III hypomineralized Amelogenesis Imperfecta. Conclusion: Rehabilitative treatment of AI in growing and developing patients will be aimed at early and comprehensive intervention to resolve esthetic and functional appearance, avoid social and emotional repercussions and accompany patients and their families (AU)

A practical method for use in epidemiological studies on enamel hypomineralisation.

With the development of the European Academy of Paediatric Dentistry (EAPD) judgment criteria, there has been increasing interest worldwide in investigation of the prevalence of demarcated opacities in tooth enamel substance, known as molar-incisor hypomineralisation (MIH). However, the lack of a standardised system for the purpose of recording MIH data in epidemiological surveys has contributed greatly to the wide variations in the reported prevalence between studies. The present publication describes the rationale, development, and content of a scoring method for MIH diagnosis in epidemiological studies as well as clinic- and hospital-based studies. The proposed grading method allows separate classification of demarcated hypomineralisation lesions and other enamel defects identical to MIH. It yields an informative description of the severity of MIH-affected teeth in terms of the stage of visible enamel destruction and the area of tooth surface affected (i.e. lesion clinical status and extent, respectively). In order to preserve the maximum amount of information from a clinical examination consistent with the need to permit direct comparisons between prevalence studies, two forms of the charting are proposed, a short form for simple screening surveys and a long form desirable for prospective, longitudinal observational research where aetiological factors in demarcated lesions are to be investigated in tandem with lesions distribution. Validation of the grading method is required, and its reliability and usefulness need to be tested in different age groups and different populations.

Genetic heterogeneity of autosomal dominant amelogenesis imperfecta demonstrated by its exclusion from the AIH2 region on human chromosome 4Q.

Amelogenesis imperfecta (AI) is a group of hereditary enamel defects, characterized by large clinical diversity. On the basis of differences in clinical manifestation and inheritance pattern, 14 different subtypes have been recognized. A locus for autosomal dominant AI (ADAI) of local hypoplastic type was recently mapped to the region between D4S392 and D4S395 on the long arm of chromosome 4. To test whether the chromosome 4 locus is responsible for other forms of AI as well, a linkage study was carried out with 17 families representing at least five clinical forms of ADAI. Admixture tests for heterogeneity performed with the marker D4S2456 gave statistical support for genetic heterogeneity of ADAI with the odds 78:1. Linkage to the ADAI locus on chromosome 4q (AIH2) could only be demonstrated with families expressing the local hypoplastic type, and there was no support for heterogeneity within that group of families. Furthermore, linkage could be excluded for five families with other clinical forms of ADAI. The data therefore demonstrated that ADAI is genetically heterogeneous, and that at least two loci for it exist.

The enamel proteins in human amelogenesis imperfecta.

Amelogenesis imperfecta comprises a unique group of hereditary conditions that result in abnormal enamel development. The purpose of this study was to characterize the enamel proteins in different amelogenesis imperfecta types and to determine if amelogenin, the principal matrix protein in normal developing enamel, was retained. Primary and/or permanent amelogenesis imperfecta teeth were analysed from 11 individuals. Normal teeth served as controls. Thin sections were cut with a diamond blade and enamel was dissected for analysis. The enamel proteins were characterized by amino acid analysis, sodium dodecyl sulphate polyacrylamide gel electrophoresis, and Western blot analysis using antiamelogenin antibodies. An increased protein content was seen in all hypocalcified and hypomaturation amelogenesis imperfecta cases. A slightly increased protein content was seen in two of four hypoplastic amelogenesis imperfecta cases. The enamel protein amino acid composition varied between the different amelogenesis imperfecta types. All three cases of hypomaturation amelogenesis imperfecta enamel showed an increased proline content compared with normal enamel or other amelogenesis imperfecta types. Hypocalcified amelogenesis imperfecta enamel had an increased tyrosine content while the other amino acids were generally similar in amount to normal enamel. Fully developed hypomaturation and hypocalcified amelogenesis imperfecta enamel showed cross-reactivity to antiamelogenin antibodies while normal enamel did not. Although both amelogenesis imperfecta types showed cross-reactivity, the banding patterns on Western blot analyses were markedly different. This investigation provides additional evidence that abnormal post-secretory processing of amelogenin is involved in hypomaturation and hypocalcified amelogenesis imperfecta. Furthermore, these results indicate that amelogenin retention can occur in a variety of amelogenesis imperfecta types. The unique amino acid compositions and distinct enamel protein species seen by electrophoresis and Western blot analyses suggest that different developmental processes might be involved in hypomaturation and hypocalcified amelogenesis imperfecta.

A nomenclature for X-linked amelogenesis imperfecta.

Mutations of the X-chromosome amelogenin gene (AMELX) are associated with amelogenesis imperfecta (AI) phenotypes (OMIM no. 301200). Currently, 12 different AMELX mutations have been identified in individuals with abnormal enamel characteristic of AI. A notable feature of AI is the variable clinical phenotype, spurring interest in genotype-phenotype correlations. It is important that researchers and clinicians have an informative and reliable means of reporting and communicating these molecular defects. Therefore, the purpose here was to present a systematic nosology for reporting the genomic, cDNA and protein consequences of AMELX mutations associated with AI. The proposed nomenclature adheres to conventions proposed for other conditions and can be adopted for the autosomal forms of AI as the molecular basis of these conditions becomes known.

Hereditary aspects and classification of hereditary amelogenesis imperfecta.

In an epidemiologic study in the middle of Sweden comprising 425 000 children age 3-19 yr, 105 children were diagnosed as having hereditary amelogenesis imperfecta (HAI). The material then was primarily classified upon clinical criteria into different subgroups either associated to a hypoplastic or to a hypomineralized type of HAI. Analyzing available genetic data obtained from 95 children in 76 families and further 11 adults in 10 families, eight different entities of HAI could be identified in a classification of HAI. In both of the basic types of HAI, the hypoplastic and the hypomineralized, autosomal dominance was the most common mode of inheritance, even if an autosomal recessive inheritance could be identified in some of the subgroups of HAI. The hypoplastic type (rough-pitted), autosomal dominance with incomplete penetrance was dominating in the material, 47 out of 105 cases. The clinical classification seemed to be relevant when testing the material on a genetic basis showing that the clinical criteria provide a strong support for a classification of HAI.

Evaluation of oral and systemic manifestations in an amelogenesis imperfecta population.

OBJECTIVES: The aim of this investigation was to describe the dental and craniofacial characteristics of patients with amelogenesis imperfecta (AI). METHODS: The study group included 43 patients(33 female and 10 male) with a mean age of 11.4+/-2.6 years. A panoramic and a cephalometric radiograph were obtained from each of these patients. Clinically AI cases were divided into four main groups according to Witkop. All patients were evaluated for chronological, bone and dental age. The patients who had severe retarded bone age were evaluated for plasma growth hormone(GH) concentrations. RESULTS: Dental and bone ages were retarded with respect to chronological age in five patients. Dental maturity and tooth eruption were not age- appropriate in some of our patients. In type III AI patients a delay in skeletal age was observed. Severe late eruption was seen in 3 patients, severe delay in dental maturity was noted in patients with type IV AI. Dental age was clinically lower in GH-deficient subjects, and skeletal age was consistently more retarded than dental age when compared to chronological age. Anterior open bite was present in both primary and permanent dentitions of 50% of the patients with type I AI, 30.8% of the patients with type II AI, and 60% of type III AI. CONCLUSION: It is concluded that the primary structure for the classification of AI be based on the mode of inheritance, with the clinical and radiographic appearances (and any other features such as systemic findings) being the secondary discriminators.

Immunochemical and biochemical characteristics of enamel proteins in hypocalcified amelogenesis imperfecta.

Amelogenesis imperfecta is a hereditary disease of the enamel that is unassociated with generalized defects. Cases of the condition are clinically classified into three groups: hypoplastic, hypomaturation, and hypocalcified. In this study, soluble protein fractions of the enamel from three patients with hypocalcified amelogenesis imperfecta were examined through the use of immunochemical and biochemical techniques. In immunochemical analyses done with a polyclonal anti-amelogenin antibody, all samples from enamel in which there was amelogenesis imperfecta were found to contain considerable amounts of amelogenin peptides. When an enamel sample from one patient was examined by Western-blot transfer and immunobinding analysis, the amelogenin fraction was found to consist of a 26-kDa molecule thought to be normally present in the outer layer of secretory-stage enamel. This enamel was also found to contain albumin as one of the major constituents of the protein fraction. These results suggest that hypocalcified amelogenesis imperfecta may in part be caused by a disturbance in matrix protein degradation during the maturation phase.

Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta.

PURPOSE: The purpose of this study was to characterize the phenotype in 9 families with autosomal recessive amelogenesis imperfecta (ARAI), and to propose a classification system allowing inclusion and delineation of diverse ARAI phenotypes. STUDY DESIGN: Nine families with ARAI were evaluated clinically and radiographically. Exfoliated and extracted teeth were examined via light and scanning electron microscopy, with the enamel in one case evaluated by amino acid analysis. RESULTS: The 9 families demonstrated diverse ARAI phenotypes including localized hypoplastic, generalized thin hypoplastic, hypocalcified and hypomaturation AI types. CONCLUSIONS: Some ARAI phenotypes observed in this study and reported in the literature cannot be classified using currently accepted ARAI nomenclature. Therefore, we propose a revised nomenclature permitting both classification of all ARAI clinical forms and inclusion of anticipated molecular-based nomenclature, such as now exists for some X-linked and autosomal dominant AI subtypes.

Clinical diagnosis and management strategies of amelogenesis imperfectavariants.

Amelogenesis imperfecta (AI) is a group of inherited disorders primarily affecting dental enamel. Variants of AI generally are classified as hypoplastic, hypocalcified, or hypomaturation types based on the primary enamel defect. The aim of this study was to analyze the clinical presentations, diagnostic features, and clinical complications of different variants of AI. Thirty-two patients from 17 families with several subtypes of AI were studied. The results showed that distinctive clinical features may be observed in each variant. However, all AI patients suffered common clinical problems of poor esthetics, teeth sensitivity, and loss of occlusal vertical dimension. The mildest problems were found in the pitted hypoplastic type whereas the most severe problems were encountered in the hypocalcified type of AI. Management strategies include composite resin veneers and jacket crowns for anterior teeth as well as steel crowns for posterior teeth. Knowledge of the clinical features and dental complications of each variant of AI helps in the diagnosis of the condition and allows institution of early preventive measures.

Amelogenesis imperfecta--multidisciplinary management from eruption to adulthood. Review and case report.

Amelogenesis imperfecta (AI) is a group of hereditary conditions that affect enamel formation. It is associated with a high morbidity for the patients and may present major restorative and sometimes orthodontic challenges for the dental team. Early recognition followed by appropriate preventive and restorative care is essential in the successful management of AI. A multidisciplinary approach with careful planning from early childhood will maximise the treatment options available for the permanent dentition and optimise the final outcome. In this case, a team consisting of two paediatric dentists, an orthodontist, a restorative dentist, and an oral and maxillofacial surgeon were involved in the management of the patient over a 12-year period. Treatment included preventive advice, interim composite restorations, two phases of orthodontic treatment, orthognathic surgery and placement of cast crowns. The patient is extremely happy with the result.