Journal of craniofacial genetics and developmental biology最新文献

Retinoic acid is known to perturb craniofacial development and can be used to understand processes controlling early embryonic development of the face. The effects of retinoic acid on mouse craniofacial development were studied by administration of a single dose (25-200 mg/ kg) of all-trans retinoic acid (RA) to timed pregnant C57BL6/J mice at gestational days (gd) 8.25, 9, or 10. RA exposure on gd 8.25 or gd 10 resulted in craniofacial defects in fetuses but gd 9 exposure revealed a differential effect of RA depending upon whether tissues were derived from branchial arch or frontonasal neural crest. Embryos exposed to RA at gd 9 showed a dose-dependent effect of RA on branchial arch derived tissues; first arch derivatives were most severely affected with the mandible and zygoma becoming severely dysplastic at the highest dose of RA (200 mg/kg). However, RA exposure on gd 9 completely spared frontonasal neural crest-derived tissues. Paired premaxillae nasal and frontal bones as well as the cartilaginous nasoethmoid region and nasal capsule containing the osseous vomer showed no statistical difference from those of control animals. These studies showed a temporal and differential sensitivity to RA and may suggest a developmental heterogeneity of the cephalic neural crest cells destined to participate in formation of craniofacial structures.

This study is the first presentation of three-dimensional computed tomography (3D-CT) for the in vitro evaluation of the prenatal human cranium. The study was based on CT examinations from 26 aborted normal fetuses between 10 and 25 weeks gestational age. Incremental coronal and transverse CT slices of 1 mm thickness and a threshold segmentation algorithm were used to generate 3D-CT reconstructions (surface-shaded display, SSD) of the cranial bones similar to their anatomical appearance. The threshold of the segmentation algorithm was selected after comparison of the 3D-CT images generated with varying thresholds and graphically reconstructed histological serial sections of particular sutures in five specimens. The variation of the segmentation threshold resulted in alterations of the bone sizes and suture widths. However, 3D-CT images allowed sensitive identification of the cranial ossification centers and accurate evaluation of the bone topography. Cutting and rotating procedures made it possible to evaluate all imaged bones in arbitrary views without disturbing superpositions, thus making isolated examinations of particular macroscopic sections of the specimens unnecessary. In conclusion, 3D-CT of the fetal cranium promises to be of considerable help in the evaluation of prenatal cranial development.

Eighteen patients with Crouzon syndrome were evaluated for anomalies of the feet. Clinical examination was unremarkable in all cases. Radiographs were evaluated by a radiologist with an interest in skeletal dysplasia, along with the craniofacial team. A range of radiographic anomalies was seen, with the phalanges, metacarpals, and tarsals all displaying anomalies. Only three cases had radiographically normal feet. These findings suggest that the effects on the feet, which, although subtle and not well described in the literature, are notable. Feet anomalies also occur with the other complex craniosynostosis syndromes resulting from mutations of fibroblastic growth factor receptor 2 molecule, such as those of Apert, Pfeiffer, and Jackson-Weiss syndromes.

The aim of the present study was to describe and pathologically evaluate an apparently unreported craniofacial malformation, based on comparison of the cranial midsagittal components with similar components under normal developmental conditions. A severely malformed fetus with a gestational age of about 17 weeks underwent whole body and special craniofacial radiography. Following autopsy dissection, the midsagittal segment of the cranial base, including the eyes, was radiographed in different projections. Midsagittal tissue blocks were serially sectioned for microscopy. Routine stains and immunohistochemical stains were applied. The face was characterized by hypertelorism, absence of external nose but with open shell-like cavities medio-cranially to the eyes, and by a palate fused in the midline and with extensive bony ridges laterally. There was absence of normal nasal cavities, presence of nasal septum and vomer, normal eyes, and nasal ducts covered with nasal mucosa ending blindly in the cartilage. No olfactory bulbs were found. The palatal ridges consisted of bony tissue. The pituitary gland was severely malformed and consisted solely of adenopituitary gland tissue, located in its full extent in the pharyngeal mucosa. There was no sella turcica. From a pathogenetic point of view, it is suggested that the neural crest cells in the frontonasal region of the crest were reduced in amount or late in migration to the midfacial region compared to the neural crest cells to the maxillary region. Therefore, we believe that the malformations observed in the nasal placodes and in the pituitary placode, combined with abnormal migration or abnormal timing of neural crest cells during the craniofacial development, are important factors behind this disorder.

Using data from three registries of congenital anomalies based on a total of more than 5 million births, some epidemiological characteristics were studied for 8,315 infants with cleft lip and/or cleft palate. There was a racial variation in the rate of cleft lip/palate within the California program but also a marked difference in rate between the three programs-France, Sweden, and California-that is probably not mainly a result of variable ascertainment but of real differences between the populations. The main analysis was made on cases without a known chromosome anomaly. The classical sex distribution was found with an excess of males at cleft lip/ palate. The sex ratio was lower (= more normal) when associated nonfacial malformations existed. Pierre Robin type cleft palate had a near-normal sex distribution while other types of cleft palate had the usual excess of females. Twinning was increased for all facial clefts irrespective of type but was more common when nonfacial associated malformations were present than when the cleft was isolated. Among cases with isolated clefts, the total twin increase was not statistically significant but the proportion of monozygotic twins was increased. There was a U-shaped maternal age relationship for cleft lip/palate that was not seen for median cleft palate (although an indicated increased risk for infants of teen-age mothers existed). For all types of cleft, there was an increased risk at high parity also after standardization for maternal age.

Using data from a French, the Swedish, and the California registries of congenital anomalies based on a total of more than 5 million births, the presence of nonfacial malformations in infants with cleft lip or cleft palate was studied. Cleft lip was less often associated with chromosome anomalies than cleft lip with cleft palate, but when all cleft lip/palate infants were compared with all infants with median cleft palate, chromosome anomalies were equally common. Ascertainment of chromosome anomalies in infants with facial clefts varied among programs. One hundred and twenty-one infants with non-chromosomal syndromes were identified-also, for these a marked variability between programs existed. An analysis of the type of associated malformations was made, comparing cleft lip/palate and median cleft palate infants. Some associations specific for the cleft types were described but to a large extent similar associations were found irrespective of cleft type. This may indicate that under certain circumstance, the various cleft types may have similar causes.

The quantification of total tooth structure derived from X-rays of Vietnamese, Southern Chinese, Mongolians, Western Eskimos, and Peruvian pre-Inca (Huari Empire) populations was used to examine dental divergence and the morphogenetics of change. Multivariate derived distances between the samples helped identify a quasicontinuous web of ethnic groups with two binary clusters ensconced within the web. One cluster was composed of Mongolians, Western Eskimos, and pre-Inca, and the other group consisted of the Southern Chinese and Vietnamese. Mongolians entered the quasicontinuum from a divergent angle (externally influenced) from that of the Southeast Asians. The Chinese and pre-Inca formed the polar samples of the distance superstructure. The pre-Inca sample was the most isolated, its closest neighbor being the Western Eskimos. Univariate and multivariate analyses suggested that the pre-Inca, whose ancestors arrived in America perhaps approximately 30,000 years ago, was the least derived sample. Clearly, microevolutionary change occurred among the samples, but the dental phenotype was resistant to environmental developmental perturbations. An assessment of dental divergence and developmental biology suggested that the overall dental phenotype is a complex multigenic morphological character, and that the observed variation evolved through total genomic drift. The quantified dental phenotype is greater than its highly multigenic algorithm and its development homeostasis is tightly controlled, or canalized, by the deterministic organization of a complex nonlinear epigenetic milieu. The overall dental phenotype quantified here was selectively neutral and a good character to help reconstruct the sequence of human evolution, but if the outlying homeostatic threshold was or will be exceeded in antecedents and descendants, respectively, evolutionary saltation occurs.

We describe a developmental dentin disorder distinct from dentin defects characterized thus far. The proband was a 9-year-old boy who was the only family member known to be affected in five generations. The dental defect was not associated with any general disease or developmental disorder. The teeth appeared normal with the exception of the pink hue seen in some primary teeth. Radiographs showed pathological resorption of primary teeth and abnormally shaped pulp chambers and denticles in permanent teeth. Root canals were wide in developing teeth, but appeared thin in erupted teeth. Histological examination of two primary molars revealed canal-like defects in dentin. In the crown, the canals appeared as clusters, which alternated with columns of normal tubular dentin, and in the virtually atubular root dentin they were haphazardly distributed. Scanning electron microscopic examination confirmed the distribution pattern of the canals. In transmission electron microscopy, the defects were found to contain symmetrically banded, segmental collagenous structures. The canal contents immunostained with antibodies to the N-terminal propeptide of type I procollagen, suggesting retention of the propeptide extension in type I collagen. Whereas type III collagen reactivity was barely detectable in the canal region, staining for type V collagen and the non-fibril-forming type VI collagen was strong. The findings imply that the pathogenesis of the defect could be related to a local failure of odontoblasts to produce normal dentin matrix.

Craniofacial growth and development involve both size and shape variations. Shape variations can be assessed independently from size using mathematical methods such as the elliptic Fourier analysis, which allows a global evaluation of the shape of organs identified by their outlines independently from size, spatial orientation, and relation to reference planes. The mandibular outlines were digitized from the tracings of the Bolton standards (lateral view) from 1 to 18 years of age, and the age differences in shape independently from size were quantified using the elliptic Fourier series. A "morphologic distance" MD (i.e., a measurement of differences in shape) between each younger mandible and the oldest one was computed using the relevant Fourier coefficients like the cartesian coordinates in standard metric measurements. MD equals 0 when the profiles are identical. MD (Y) between the Bolton standard at 18 years of age and all the other Bolton tracings were significantly correlated (correlation coefficient r = 0.987, P < or = 0.001) with age (X) (semi-logarithmic interpolation Y = -3.87.log(e) X + 13.593). Differences between the size-independent shape of the Bolton standard at 18 years and the relevant plot at 1 year were located at the chin, gonion, coronoid process, anterior border of the ramus. Size differences were measured from the areas enclosed by the mandibular outlines. Mandibular area (Y) increased about 2.58 times from 1 to 18 years of age (X) (Y = -0.071.X2 + 4.917.X + 35.904, r = 0.997, P < or = 0.001). The shape effect was largely overwhelmed by the very evident size increments, and it could be measured only using the proper mathematical methods. The method developed could also be applied to the comparison between healthy and diseased individuals.

The hand radiographs of fifteen patients with a diagnosis of Saethre-Chotzen syndrome were reviewed by a radiologist with an interest in skeletal dysplasia along with the craniofacial team. Eleven patients exhibited a range of bone abnormalities of the following sites: thumbs, fingers, metacarpals, and the radius. The epiphysis of the distal phalanx of the thumb was most commonly involved site with 7 of the 15 patients affected. In addition to the structural abnormalities all cases before puberty (14 out of 15 patients in this series) showed variable delay of the bone age.