J. Tim Wright

Analysis of the tricho‐dento‐osseous syndrome genotype and phenotype

The tricho-dento-osseous (TDO) syndrome demonstrates kinky curly hair, thin-pitted enamel, taurodontism, and thickening of cortical bone. The purpose of this investigation was to characterize the phenotypic variation of TDO in 3, previously unreported, kindreds and to examine possible candidates for the genomic TDO locus. Thirty-three affected and 20 unaffected individuals were recruited for prospective analysis. Participants were evaluated clinically and photographed by one examiner. Blood was drawn for genetic linkage analyses and radiographs were taken to assess dental and skeletal characteristics. All TDO individuals with teeth had generalized thin and/or pitted enamel hypoplasia. Taurodontism was present in all affected individuals, but was variably expressed. Unique kinky/curly hair at birth was reported in 85% of affected individuals. The curly hair phenotype was retained in 46% of affected individuals after infancy. Thick cranial bones, lack of visible pneumatization of the mastoid process, and/or obliteration of the calvarial diploë was seen in 97% of affected persons compared with 30% of the unaffected individuals. The findings suggest that curly hair at birth, enamel hypoplasia, and taurodontism are highly penetrant yet clinically variable components of TDO. The ABO, Kell, and Gc loci previously suggested to be linked to TDO were excluded as candidates in this TDO population. This investigation characterizes the marked variability in the expression of skeletal, hair, and dental manifestations. The broad range of TDO phenotypes seen in these families, including a variety of skeletal changes, does not support subdividing TDO into multiple subtypes based on subtle phenotypic differences.

Dental anomalies associated with amelogenesis imperfecta: A radiographic assessment

Amelogenesis imperfecta, a group of hereditary conditions primarily affecting the enamel, has been associated with dental anomalies, including taurodontism, congenitally missing teeth, delayed eruption, crown resorption, and abnormal enamel density. The purpose of this study was to assess the prevalence of these anomalies in an amelogenesis imperfecta population. The study group consisted of members of 9 unrelated families--22 family members with amelogenesis imperfecta and 13 unaffected family members. Panoramic radiographs were evaluated for taurodontism, congenitally missing teeth, delayed tooth eruption, pathologic dental resorption, pulp calcification, and radiographic enamel density. The prevalence of taurodontism was similar in people with amelogenesis imperfecta and normal people; all of the remaining parameters were more commonly observed in people with amelogenesis imperfecta. The radiographic enamel density was quantitatively reduced in teeth affected by amelogenesis imperfecta in comparison with teeth with normal enamel. These findings suggest that some of the features associated with amelogenesis imperfecta result from abnormal enamel formation (eg, decreased enamel density, crown resorption) whereas others may occur as a result of expression of the genetic mutation in cells other than ameloblasts (eg, abnormal eruption, pulp calcification).

Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the proteins phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

Tricho-dento-osseous syndrome: Features of the hair and teeth

Tricho-dento-osseous syndrome is a rare autosomal dominant hereditary disorder characterized by curly hair, enamel hypoplasia, taurodont teeth, and thickened cortical bone. A large kindred with this syndrome has been identified in North Carolina and characterized by pedigree analysis and clinical evaluation. Hair samples (N = 3) and an exfoliated primary tooth (N = 1) from persons with tricho-dento-osseous syndrome and hair and teeth from unaffected persons were examined. Scanning electron microscopy showed that the hair shaft morphology, diameter, and cuticular pattern and periodicity were similar for the tricho-dento-osseous syndrome and control samples. The affected tooth was examined using light microscopy and a scanning electron microscope that showed pitting hypoplasia of the enamel surface, an extremely large pulp chamber, and dentin that appeared structurally normal. The affected enamel was uniformly thin, only 10% the thickness of the control enamel. The bulk of this enamel showed no prism formation. This study indicates that although hair with tricho-dento-osseous syndrome often is clinically curly, it can be straight, and it does not appear to have unique ultrastructural features that are of diagnostic benefit. The dental characteristics of tricho-dento-osseous syndrome were the most consistent feature seen in this kindred.

Enamel ultrastructure and protein content in X-linked amelogenesis imperfecta

X-linked amelogenesis imperfecta has been proven in a number of families to be linked to or involve a variety of mutations in the X chromosome amelogenin gene. The purpose of this study was to characterize the enamel ultrastructure and enamel protein in a kindred affected by X-linked amelogenesis imperfecta. Exfoliated primary teeth were obtained from two related persons (one male, one female) who had X-linked amelogenesis imperfecta with marked hypoplasia. Normal enamel (age and sex matched) was used as the control for all analyses. The teeth were evaluated using light microscopy, scanning electron microscopy, and microradiography. The enamel of the heterozygous female was hypoplastic and rough with marked surface depressions. Enamel beneath these depressions was poorly organized and lacked a prismatic structure. The affected male had very thin enamel (approximately 40 microns) that also lacked an organized structure. Enamel protein from the teeth of the heterozygous female and the control was characterized using amino acid analysis. The protein content of the enamel of the female with amelogenesis imperfecta was 0.40% (N = 1) whereas the control enamel ranged from 0.17% to 0.45% (N = 4; mean = 0.34%). This study indicates that although the enamel in both the male and female with X-linked amelogenesis imperfecta displayed marked structural abnormalities the enamel protein was similar in quantity and amino acid composition for normal and X-linked amelogenesis imperfecta (female) enamel.(ABSTRACT TRUNCATED AT 250 WORDS)

Craniofacial morphology of the tricho-dento-osseous syndrome

Tricho‐dento‐osseous syndrome (TDO) is characterized by abnormal bone, hair, and tooth morphology. However, the reported craniofacial abnormalities are not well characterized. The purpose of this study was to compare the craniofacial parameters of 25 subjects affected with TDO (A) with those of 15 unaffected relatives (U). Standardized lateral cephalograms were traced and digitized. Each subjects data were compared by age and sex to cephalometric standards (Bolton, Behrents); severity was scored by standard deviations from the standard mean, and then grouped into A vs. U. All cephalograms were evaluated for frontal sinuses, mastoid pneumatization, diploe, and bone density, and cranial thickness was measured. Cranial base length (SN; NBa), cranial base angle (BaSN), and mandibular body length (GoPg) were greater in A than in U (p < 0.05). Both groups had longer total and lower facial heights (NMe; ANSMe) compared with normal standards. Frontal sinuses, mastoid pneumatization and diploe were visible less often in A than in U (p < 0.05). Parietal bone and bone at lambda was significantly thicker (p < 0.05) in A than in U. Variability was substantial in many measures in both A and U. The major TDO craniofacial features involve the cranial base, mandibular body length, absence of visible pneumatized mastoids, frontal sinuses and diploe, and thicker cranial bone.

Genomics of Dental Caries and Caries Risk Assessment

Our understanding of dental caries was transformed over the past century to recognize that this chronic disease is an infectious and complex condition involving host, biofilm, and environmental factors. The severity and distribution of dental caries, or its clinical phenotype, is highly variable in the population. During the past 20 years, the genomic era has provided new insights into the interactions of host, oral flora, and environmental factors that make dental caries similar to many other complex hereditary conditions. Our knowledge of the contributions of an individual’s genome to their risk and resistance to dental caries has grown tremendously over the past decade. New insights continue to be gained as our understanding of the interactions between our genome, oral microbiome, microbial metabolomics, and environmental influences advances. Knowledge of, and the ability to predict, these underlying determinants of disease and health will ultimately provide approaches to accurately predict risk and activity of dental caries in an individual, allowing personalized approaches to preventing and managing this common disease of humans.

Heritable Conditions Affecting Tissues of the Oral Cavity

The oral cavity is made up of complex and diverse tissues that provide a variety of highly specialized functions ranging from nuerosensory (e.g., taste) to nutritional/digestive functions (e.g., salivary digestion and mastication). Not surprisingly there is a substantial portion of the human genome used in making these unique diverse structures and allowing them to function appropriately. Consequently there are hundreds of conditions affecting the soft and hard tissues of the oral cavity. Some of these conditions affect primarily or only the oral cavity, although others are associated with significant somatic manifestations. This chapter reviews some of these conditions providing the reader a framework for understanding hereditary pathologies of the oral cavity.