The patient with recurrent oral ulceration.

This paper discusses the range of recurrent oral ulceration which affects the oral mucosa. Types of ulceration covered in this paper include traumatic, infective, aphthous, ulceration related to the oral dermatoses, drug-induced, ulceration as a manifestation of systemic disease and ulceration indicating malignancy. Aspects of the aetiology, diagnosis and management of common oral recurrent ulcerative conditions are reviewed from a clinical perspective as an aid to practising dentists.

Relationship of phenotype and genotype in X-linked amelogenesis imperfecta.

X-linked amelogenesis imperfectas (AI) resulting from mutations in the amelogenin gene (AMELX) are phenotypically and genetically diverse. Amelogenin is the predominant matrix protein in developing enamel and is essential for normal enamel formation. To date, 12 allelic AMELX mutations have been described that purportedly result in markedly different expressed amelogenin protein products. We hypothesize that these AMELX gene mutations result in unique and functionally altered amelogenin proteins that are associated with distinct amelogenesis imperfecta phenotypes. The AMELX mutations and associated phenotypes fall generally into three categories. (1) Mutations (e.g., signal peptide mutations) causing a total of loss of amelogenin protein are associated with a primarily hypoplastic phenotype (though mineralization defects also can occur). (2) Missense mutations affecting the N-terminal region, especially those causing changes in the putative lectin-binding domain and TRAP (tyrosine rich amelogenin protein) region of the amelogenin molecule, result in a predominantly hypomineralization/hypomaturation AI phenotype with enamel that is discolored and has retained amelogenin. (3) Mutations causing loss of the amelogenin C terminus result in a phenotype characterized by hypoplasia. The consistent association of similar hypoplastic or hypomineralization/hypomaturation AI phenotypes with specific AMELX mutations may help identify distinct functional domains of the amelogenin molecule. The phenotype-genotype correlations in this study suggest there are important functional domains of the amelogenin molecule that are critical for the development of normal enamel structure, composition, and thickness.

Unusual manifestations in X-linked amelogenesis imperfecta.

This paper describes a female with X-linked amelogenesis imperfecta (XAI). This case is unusual in having taurodontism, pulpal calcifications, coronal defects prior to tooth eruption and unerupted teeth. These findings have been reported in some cases of autosomal dominant and autosomal recessive AI but have not previously been documented in XAI.

Amelogenesis imperfecta: a classification and catalogue for the 21st century.

Amelogenesis imperfecta (AI) is a collective term for a number of conditions with abnormal enamel formation. Many cases are inherited, either as an X-linked, autosomal dominant or autosomal recessive trait. Several classifications have evolved since 1945, based primarily on phenotype with the mode of inheritance being used in some systems as a secondary factor in allocating a case into a particular category. The benefits and shortcomings of these systems are reviewed. As we move into an era of establishing the molecular basis of AI we propose a robust mechanism for classification and cataloguing of the disorder which parallels systems used in medical genetics. This system is applicable to individuals and families irrespective of current or future knowledge of the molecular defect involved. We argue that this system is of more benefit to these individuals and families than previous classifications.

Juvenile mandibular chronic osteomyelitis: a distinct clinical entity.

Sclerosing osteomyelitis of the mandible is an uncommon disease of unknown aetiology. A series of eight female children (6 to 12 years old) with a distinct mandibular inflammatory disease were studied. Each presented with pain and a recurrent soft tissue swelling overlying a predominantly unilateral mandibular enlargement. On imaging, this deformity demonstrated a mixture of patchy sclerosis and radiolucency. A raised erythrocyte sedimentation rate was the only consistent serological finding. Treatment varied from symptomatic control with non-steroidal anti-inflammatory medication, to surgical management that included decortication and contouring and, in one case, resection with reconstruction. A potential protocol for treatment of this disease is given. The early age of onset of the disease process and the uniformity of the features distinguish this condition from other groups of disorders that, previously, have been collectively designated as chronic diffuse sclerosing osteomyelitis. It is proposed that this inflammatory disease of mandibular bone, in the paediatric patient, should be regarded as a separate clinical entity: 'juvenile mandibular chronic osteomyelitis'.

Molecular analysis for genetic counselling in amelogenesis imperfecta.

OBJECTIVE: To use molecular genetics to establish the mode of inheritance in a family with amelogenesis imperfecta. MATERIALS AND METHODS: The polymerase chain reaction was used to amplify exons of the amelogenin gene on the short arm of the X chromosome. RESULTS: A single base deletion mutation in exon 6 of the amelogenin gene was identified. This mutation was a single base deletion of a cytosine residue - 431delC - in codon 96 of exon 6, introducing a stop codon 30 codons downstream of the mutation in codon 126 of the exon. CONCLUSION: The firm establishment of an X-linked mode of inheritance affects the genetic counselling for this family.

Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations.

Amelogenin, the predominant matrix protein in developing dental enamel, is considered essential for normal enamel formation, but its exact functions are undefined. Mutations in the AMELX gene that encodes for amelogenin protein cause X-linked amelogenesis imperfecta (AI), with phenotypes characterized by hypoplastic and/or poorly mineralized enamel. Eight different AMELX deletion and substitution mutations have been reported to date. The purpose here was to evaluate the genotype and phenotype of two large kindreds segregating for X-linked AI. Phenotypically affected males in family 1 had yellowish-brown, poorly mineralized enamel; those in family 2 had thin, smooth, hypoplastic enamel. Heterozygous females in both kindreds had vertical hypoplastic grooves in their enamel. DNA was obtained from family members; exons 1-7 of AMELX were amplified and sequenced. Mutational analysis of family 1 revealed a single-base-pair change of A-->T at nucleotide 256, resulting in a His-->Leu change. Analysis of family 2 revealed deletion of a C-nucleotide in codon 119 causing a frameshift alteration of the next six codons, and a premature stop codon resulting in truncation of the protein 18 amino acids shorter than the wild-type. To date, all mutations that alter the C-terminus of amelogenin after the 157th amino acid have resulted in a hypoplastic phenotype. In contrast, other AMELX mutations appear to cause predominantly mineralization defects (e.g. the mutation seen in family 1). This difference suggests that the C-terminus of the normal amelogenin protein is important for controlling enamel thickness.

Clinical and radiographic features of a family with autosomal dominant amelogenesis imperfecta with taurodontism.

This paper describes the clinical features of a family of four generations with autosomal dominant amelogenesis imperfecta with taurodontism (ADAIT). Considerable variation in phenotype was seen, both between individuals and within the dentition of some individuals. Many of the adults had received extensive dental restorative work. These findings re-enforce previous observations of variable phenotype in this and other forms of the condition and add to the argument for a revision of methods of classification. This history of this large family draws further attention to the restorative demands of this group of dental anomalies and, by their generous co-operation, will prove an invaluable help in the investigation by molecular genetic techniques of this disfiguring condition.

Solitary fibrous tumour of the oral cavity: report of two cases.

The solitary fibrous tumour is an uncommon, benign neoplasm of adults involving the pleura. It is now recognised to occur in extrapleural sites. Only a limited number of cases have been reported in the oral cavity. This paper reports two further cases, which presented as clinically benign masses in the palate and buccal mucosa respectively.

Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions.

Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) is inherited as a highly penetrant autosomal dominant trait. These dental findings are similar to those of another autosomal dominant condition, the tricho-dento-osseous syndrome (TDO), from which AIHHT differs primarily by lack of changes in the hair and bones. TDO is characterized by a highly variable clinical phenotype. While enamel hypoplasia and taurodontism appear to be present in all TDO cases, non-dental features may be absent, with approximately half of TDO cases losing the kinky/curly hair phenotype seen in infancy by adolescence, and in almost 20% of cases, osseous changes are not evident. The genetic basis for AIHHT is unknown and it has been questioned whether AIHHT and TDO are separate conditions or a spectrum of disease. The genetic basis for TDO has recently been identified as a deletion mutation in the distal-less 3 (DLX3) transcription factor gene. To determine if AIHHT and TDO represent variable expression of a common DLX3 gene mutation, allelic mutations of the DLX3 gene, or mutations in DLX7 (the linked paralogue to DLX3 on chromosome 17), we have performed mutational analysis and sequencing studies of the DLX3 and DLX7 genes in three individuals (two affected and one unaffected) from a family with AIHHT. Results of the analysis demonstrate that AIHHT and TDO are not due to a common DLX3 gene mutation. Sequence analyses of the DLX3 and DLX7 genes suggest AIHHT is not due to genetic mutations or polymorphisms in the exons of these genes. These results suggest that AI-HHT and TDO are two genetically distinct conditions.

Genetic aspects of dental disorders.

This paper reviews past and present applications of quantitative and molecular genetics to dental disorders. Examples are given relating to craniofacial development (including malocclusion), oral supporting tissues (including periodontal diseases) and dental hard tissues (including defects of enamel and dentine as well as dental caries). Future developments and applications to clinical dentistry are discussed. Early investigations confirmed genetic bases to dental caries, periodontal diseases and malocclusion, but research findings have had little impact on clinical practice. The complex multifactorial aetiologies of these conditions, together with methodological problems, have limited progress until recently. Present studies are clarifying previously unrecognized genetic and phenotypic heterogeneities and attempting to unravel the complex interactions between genes and environment by applying new statistical modelling approaches to twin and family data. Linkage studies using highly polymorphic DNA markers are providing a means of locating candidate genes, including quantitative trait loci (QTL). In future, as knowledge increases; it should be possible to implement preventive strategies for those genetically-predisposed individuals who are identified to be at risk.

Orofacial granulomatosis: a diagnostic problem for the unwary and a management dilemma. Case reports.

Orofacial granulomatosis is a condition that may be difficult to diagnose for those unfamiliar with the entity. This paper describes two cases and addresses the presentation, pathogenesis and treatment. The clinical recognition of this condition is important as is the subsequent investigation by an appropriate specialist. Management of patients needs to take into account the results of further investigations, the patient's expectations, and the severity of the condition.

Molecular biology of hereditary enamel defects.

Amelogenesis imperfecta is a disfiguring inherited condition affecting tooth enamel. X-Linked and autosomal dominant and recessive inheritance patterns occur. X-Linked amelogenesis imperfecta has been studied extensively at the molecular level. Linkage analysis has shown that there is genetic hetetogeneity in X-linked amelogenesis imperfecta with two identified loci: AIH1 and AIH3. The AIH1 locus corresponds to the location of the amelogenin gene on the distal short arm of the X chromosome; various mutations in the amelogenin gene have been found in families with X-linked amelogenesis imperfecta. The AIH3 locus maps to the Xq24-q27.1 region on the long arm of the X chromosome. Linkage to the long arm of chromosome 4 has been established in three families with autosomal dominant amelogenesis imperfecta. There is as yet no published evidence for genetic heterogeneity in autosomal dominant amelogenesis imperfecta as in X-linked amelogenesis imperfecta. Candidate genes for autosomal dominant amelogenesis imperfecta include tuftelin (1q), albumin (4q) and ameloblastin (4q) but the involvement of these genes in the disease has yet to be demonstrated. In view of the variable clinical appearances within families with autosomal dominant amelogenesis imperfecta and X-linked amelogenesis imperfecta, together with the finding that different X-linked amelogenesis imperfecta phenotypes result from mutations within the same gene, an alternative classification based on the molecular defect and mode of inheritance rather than phenotype has been proposed.