Abnormal mandibular growth and the condylar cartilage.

Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their often disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritis (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage.

DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome.

The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy-terminus of the DLX3 protein is critical in determining its function during development in these different tissues.

Quantitative histological and ultrastructural features of opercula of normally erupting human teeth.

Tooth eruption across the mucosa in humans has been studied rarely, although there are disturbances of eruption that are attributed specifically to failure of the supraosseous eruptive migration. The aim of this study was to analyze the soft tissues covering normally erupting teeth so as to get an insight into the supraosseous phase of tooth eruption and to provide the basis for comparison with cases of eruption disturbances. Six opercula covering normally erupting permanent molars (primary opercula) and six of succedaneous teeth (secondary opercula) were surgically removed from 10 patients aged 7.5-17.5 years. Specimens were examined light and electron microscopically and analyzed morphometrically. All opercula contained strands and islands of odontogenic epithelium, prominent numbers of high endothelial venules, nerves, and mast cells. Nerves comprised normally structured, 1.5-3.5 microm thick myelinated (Adelta) and thinner unmyelinated (C) fibers. In primary opercula, the proportions of blood vessels and nerves were three- and sevenfold higher than the respective values for the secondary opercula. Furthermore, primary opercula contained multinucleated, fibroblast-like giant cells that were not observed in secondary opercula. As all teeth under investigation were erupting normally, neither the presence of the giant cells nor the atypical proportions of blood vessels and nerves appeared to be decisive in the eruption process. These conspicuous tissue components of opercula seem merely to accompany the eruptive tooth movement.

Malformations of the tooth root in humans.

The most common root malformations in humans arise from either developmental disorders of the root alone or disorders of radicular development as part of a general tooth dysplasia. The aim of this review is to relate the characteristics of these root malformations to potentially disrupted processes involved in radicular morphogenesis. Radicular morphogenesis proceeds under the control of Hertwig's epithelial root sheath (HERS) which determines the number, length, and shape of the root, induces the formation of radicular dentin, and participates in the development of root cementum. Formation of HERS at the transition from crown to root development appears to be very insensitive to adverse effects, with the result that rootless teeth are extremely rare. In contrast, shortened roots as a consequence of impaired or prematurely halted apical growth of HERS constitute the most prevalent radicular dysplasia which occurs due to trauma and unknown reasons as well as in association with dentin disorders. While odontoblast differentiation inevitably stops when growth of HERS is arrested, it seems to be unaffected even in cases of severe dentin dysplasias such as regional odontodysplasia and dentin dysplasia type I. As a result radicular dentin formation is at least initiated and progresses for a limited time. The only condition affecting cementogenesis is hypophosphatasia which disrupts the formation of acellular cementum through an inhibition of mineralization. A process particularly susceptible to adverse effects appears to be the formation of the furcation in multirooted teeth. Impairment or disruption of this process entails taurodontism, single-rooted posterior teeth, and misshapen furcations. Thus, even though many characteristics of human root malformations can be related to disorders of specific processes involved in radicular morphogenesis, precise inferences as to the pathogenesis of these dysplasias are hampered by the still limited knowledge on root formation.

Hazard rates and causes of death in a captive group of crab-eating monkeys (Macaca fascicularis).

In an attempt to examine possible associations between stages of agespecific mortality and various causes of death, vital records of 159 male and 192 female crab-eating monkeys (Macaca fascicularis), housed as a single group, were analyzed. Survival and hazard rates associated with each of five distinct categories of causes of death were estimated for males and females, using the nonparametric kernel method. The obtained overall survival and hazard functions were similar to those reported previously for rhesus monkeys. Among two stages identified in age-specific mortality, the first stage, characterized by rapidly decreasing hazard rates up to about 1.5-2 years of age, was discriminated by the occurrence of deaths due to unfitness for postnatal life. The second stage lasted up to the age of 10-15 years and was largely characterized by a high incidence of violent deaths. The respective hazard rates in males and females attained peaks during the early reproductive period of life and markedly decreased thereafter. This pattern was interpreted to indicate that second stage mortality is unlikely related to senescence, but rather, seems to depend on extrinsic environmental factors. Thus, when considering overall hazard rates in Macaca fascicularis, the onset of senescence, as a result of the specific aspects of simian reproduction, may be hidden from view, and mortality due to aging may only be appreciable after 10 to 15 years of age. © 1993 Wiley-Liss, Inc.

Dental phenotype in Jalili syndrome due to a c.1312 dupC homozygous mutation in the CNNM4 gene.

Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy) and a dental disorder (amelogenesis imperfecta), which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a disrupted magnesium transport is involved in the development of the dental abnormalities observed in Jalili syndrome.

Electron microscopy.

Correlative light (LM) and transmission electron microscopic (TEM) analysis is useful, if ultrastructural details of cells need to be related to functional aspects which can only be examined at the LM level. The first protocol presented here introduces a relatively simple way of obtaining TEM images which, on the one hand, reveal ultrastructural details of individual cells and, on the other hand, are large enough to allow a correlation with light micrographs. The second protocol describes a technique for estimating mineral densities of hard tissues using backscattered electron images obtained with a scanning electron microscope. This technique can be used to analyze the mineralization processes which occur throughout tooth formation.