Human Malformed Perinatal Anthropological Crania Contribute to New Insight in the Extension of Bone Malformations in Cranial Development.

INTRODUCTION: We describe five abnormal crania which may provide more diagnostic data for assessment of abnormal crania in newborns. METHODS: Five malformed perinatal crania from the Saxtorphian Collection are described using published prenatal abnormal cranial development criteria. These malformations were compared to normal cranial development arising from the migration of neural crest cells. Visual and photographic investigations were performed. RESULTS: The malformed crania were occipital encephalocele, holoprosencephaly, anencephaly, and two without a recognizable diagnosis. The anthropological crania were malformed in the same regions as formerly observed in fetal pathology. These regions were comparable to fields formed during normal cell migration from the neural crest. This has seemingly not previously been demonstrated. One undiagnosed cranium may represent a Treacher Collins syndrome (Case 3). The other undiagnosed cranium (Case 4) could be from a scaphocephalic specimen. DISCUSSION: Sharp borderlines between malformed and non-malformed regions in cranial syndromes may enable improvement in diagnostics.

Sella turcica morphology and the pituitary gland-a new contribution to craniofacial diagnostics based on histology and neuroradiology.

The present review summarizes two decades of published and unpublished studies on normal and pathological development of sella turcica and pituitary gland in humans. The pathological conditions are studied in known genotype deviations, syndromes, and other malformations. The studies include histological analyses of human prenatal material and profile radiographic analyses of human postnatal material, supplemented in a few cases with neuroradiology. Prenatal and postnatal results are compared. Similarities between prenatal and postnatal deviations in sella turcica morphology were demonstrated. Malformations in the pituitary gland were observed in several cases. For diagnostic purposes, the review distinguishes between deviations in the anterior wall and in the posterior wall of the sella turcica. Deviations in the anterior wall seem to be associated with deviations specifically in the frontonasal developmental field, while deviations in the posterior wall are often connected with malformations in the posterior structures, e.g. the cerebellum. In normal cases, minor variations in morphology are observed. In each pathological case, a specific malformation pattern was observed in sella turcica morphology, varying from mild to severe phenotype. The malformation in the sella turcica/pituitary gland can be associated with a malformation within a developmental field that forms the craniofacial region (frontonasal, maxillary, palatal, and mandibular fields), sometimes also involving the brain stem, thymus, thyroid, and heart (velocardiofacial syndrome). Pathological sella turcica morphology can also be associated with malformations in the cerebellum and larynx (Cri-du-Chat syndrome). This review demonstrates the value of combining profile radiographic diagnostics with neuroradiological diagnostics in cases with malformed sella turcicae.

Autotransplantation of maxillary second premolars to mandibular recipient sites where the primary second molars were impacted, predisposes for complications.

OBJECTIVE: The aim of the study was to elucidate whether ankylosis of a transplanted permanent tooth can be predicted based on an evaluation of the primary and permanent dentitions. MATERIALS AND METHODS: The study comprised 162 maxillary second premolars and 49 third molars transplanted to the mandibular second premolar region in 157 patients treated in the period 1980-2003. SELECTION CRITERIA: panoramic radiograph available; agenesis of the mandibular permanent premolar/s; persistence of the primary molar at the recipient site. The 211 transplanted teeth were observed for a period of between 1-29 years. RESULTS: Seven per cent (95% confidence interval, CI = 3-11%) of the transplanted second premolars ankylosed during the first 10 years after operation. The success rate for transplantation of the third molar to the mandibular second premolar region was significantly lower (p = 0.001), as 40% (95% CI = 24-57%) of the third molars had ankylosed 10 years after operation. A significant association (p = 0.022) was found between ankylosis of a second premolar and infra-position of the primary second molar located at the recipient site. The infraposition group had 13% (CI = 4-23%) ankylosis after 10 year, whereas the non-infraposition group had 5% (CI = 1-9%) ankylosis after 10 years. CONCLUSIONS: The present study concludes that there is an increased risk of ankylosis of the transplanted permanent tooth if the primary tooth at the recipient site is in infraposition. This observation may be decisive for treatment planning, especially in young individuals in whom excessive growth of the alveolar process is expected from the cephalometric analysis.

Craniofacial morphology of the frontonasal segment in patients with one or two macrodontic maxillary central incisors.

The purpose was to describe the craniofacial morphology of the frontonasal segment in patients with one or two macrodontic central incisors. Latero-lateral head radiographs from 21 patients were analyzed. Cephalometric analyses were performed with focus on the morphology of the frontonasal segment of the cranium, including nasal bone, maxilla, thickness of the frontal bone, sella turcica, and the anterior cranial fossa. The macrodontic incisors are located in this frontonasal segment. Increased values compared with normal were observed in the following: the length of the nasal bone (P = 0.038), the thickness of the frontal bone (P = 0.003), the length of the sella turcica (P = 0.006), the cranial base angle (P = 0.036), the length of the anterior cranial fossa (P = 0.002), and the height (P = 0.042) and length (P = 0.011) of the maxilla. The prognathia of the maxilla was significantly decreased (P = 0.003). The depth of the sella turcica and the inclination of the maxilla were normal. This study is a new example of how the morphology of the dentition and the underlying jaw (the frontonasal segment) are interrelated. It is also an example of how the maxillary incisors and jaws are interrelated with the anterior cranial base, including the sella turcica morphology.

Predicting lower third molar eruption on panoramic radiographs after cephalometric comparison of profile and panoramic radiographs.

Previous studies have suggested methods for predicting third molar tooth eruption radiographically. Still, this prediction is associated with uncertainty. The aim of the present study was to elucidate the association between cephalometric measurements on profile and panoramic radiographs and to find a simple and reliable method for predicting the eruption of the mandibular third molar by measurements on panoramic radiographs. The material consisted of profile and panoramic radiographs, taken before orthodontic treatment, of 30 males and 23 females (median age 22, range 18-48 years), with no known diseases. Cephalometric measurements on panoramic and profile radiographs were performed and compared, i.e. the size of the gonial angle and sagittal distance from the alveolar margin between the mandibular central incisors to the anterior border of the mandibular ramus. Furthermore, the mesiodistal width of the second molar was measured. Statistical methods included analysis of method error. The probability of eruption was modelled using logistic regression analysis. Correlation was observed between all measurements on profile and panoramic radiographs. The skeletal variable expressing the length from the ramus to the incisors (olr-id) showed a statistically significant correlation. By combining this length with the mesiodistal width of the lower second molar, the prediction of eruption of the lower third molar was strengthened. A new formula for calculating the probability of eruption of the mandibular third molar was made and a graph constructed for easy assessment. In conclusion, a simple method for predicting the eruption of the third molar is presented.

The inter-relation between epithelial cells of Malassez and vessels studied immunohistochemically in the periodontal membrane of human primary and permanent teeth.

BACKGROUND: Only few immunohistochemical studies have focused on the periodontal membrane in human primary teeth. Recently, studies on epithelial cells of Malassez and innervation have been published. Studies on the inter-relation between vessels and the epithelial cells of Malassez are seemingly lacking. AIM: he aim of this immunohistochemical study is to describe the histological inter-relation between epithelial cells of Malassez and vessels in the periodontal membrane close to the root surface of human primary and permanent teeth. METHODS: Twenty-nine human primary teeth and 15 permanent teeth were extracted in connection with dental treatment. The teeth were fixated, embedded in paraffin, cut in serial sections and examined immunohistochemically for epithelial cells of Malassez using wide spectrum screening and vessels using Von Willebrand Factor VIII. RESULTS: The study showed that vessels and epithelial cells of Malassez are seen parallel to the root surface. The vessels are seen on that side of the epithelial cells of Malassez, which are not facing the root surface. CONCLUSION: The vascularization appeared similar in primary and permanent teeth.

Immunolocalization of RANK and RANKL along the root surface and in the periodontal membrane of human primary and permanent teeth.

OBJECTIVE: Root resorption, impaired tooth eruption and early tooth loss have been described in relation to diseases that involve defects in the RANK-RANKL-OPG-expression. The aim of the present immunhistochemical study was to localize and compare the reactions for RANK and membrane-bound RANKL along root surfaces and in the periodontal membrane in close proximity to the root surface of human primary and permanent teeth. MATERIALS AND METHODS: The material comprised extracted human teeth (11 primary teeth and six permanent teeth) from 10 different patients. Paraffin sections were prepared of each tooth and sections of each tooth were immunohistochemically stained with antibodies specific for membrane-bound RANKL and RANK. RESULTS: The root surface and the periodontal membrane in close proximity to the root surface did not show immunoreactivity for RANKL. RANKL was only located in odontoblasts and in cells along denticles in one primary tooth. RANK was located in mononuclear cells in the pulp and in multinucleated odontoclasts along resorbed root surfaces and along resorbed dentin surfaces in the pulp in primary teeth and one permanent tooth. CONCLUSIONS: This study demonstrated RANK positivity in resorption areas in primary and permanent teeth. RANKL was positive in the pulp of one primary tooth. RANK expression in odontoclasts and RANKL expression in the pulp may indicate that RANK/RANKL play a role during resorption.

Preeruptive intracoronal resorption observed in 13 patients.

INTRODUCTION: The literature on preeruptive intracoronal resorption is sparse, comprising mainly reports of single patients. This study includes 13 patients with preeruptive intracoronal resorption, forwarded for consultation regarding diagnostics and etiology. The purposes were to determine which teeth are affected by the condition and describe how the defect is manifested radiographically. METHODS: We used visual analyses of dental or panoramic radiographs. RESULTS: The mandibular second molar appears to be the tooth that is most often affected by preeruptive intracoronal resorption. The resorption of the dentin in the molar crown was in the initial phases often seen in the medial aspects. The dentin in the crown could also be completely resorbed. The enamel contour encircling the dentin persisted as shown on the radiographs. In 1 maxillary canine, the dentin and enamel structures were completely disorganized by the resorption processes. CONCLUSIONS: Specialists in orthodontics are often the first to see radiographs of unerupted permanent teeth; therefore, they have a responsibility to be aware of the condition and refer these patients to an endodontist for treatment planning and prognosis before a decision is made regarding orthodontic treatment.

Craniofacial morphology in patients with hypophosphatemic rickets: a cephalometric study focusing on differences between bone of cartilaginous and intramembranous origin.

Hypophosphatemic rickets (HR) are diseases characterized by deficient mineralization of bone due to abnormal renal wasting of phosphate. Deformation of bony structures of cartilaginous origin has been described as a major characteristic in patients with HR, but little is known about the impact on bony structures of intramembranous origin. The aim of the present study was to describe the osseous morphology of the craniofacial structures in patients with HR compared to healthy controls, and to investigate the impact of different bone origin on the osseous morphology. Fifty-three patients with HR (17 males, 36 females), aged 3-74 yrs, were included. Fifty HR patients had dominant X-linked disease, and in three patients no mutations were identified. A total of 79 healthy individuals (37 males, 42 females), aged 6-79 yrs, with normal occlusion served as controls. Significant cephalometric differences were found between HR patients and controls. In HR patients, the cranial base was flattened and the depth of the posterior cranial fossa was decreased. The anterior height of the cranium, the angle nasion-sella-frontale, and the thickness of theca were increased. The length of the nasal bone and the height of the maxilla were reduced. In contrast, the vertical as well as the sagittal relation between the jaws were unaffected in HR patients compared to controls. In conclusion, we found that the cranial structures of cartilaginous origin as well as the structures of intramembraneous origin were affected in patients with HR.

A retrospective overview of treatment choice and outcome in 126 cases with arrested eruption of mandibular second molars.

The purpose of the present retrospective study was to analyze treatment choice and outcome in patients with retention/impaction of the mandibular second molar. Radiographic material, from three large clinics, from 106 patients (60 males and 46 females) with 126 retained/impacted permanent mandibular second molars treated during the years 1985-2005 was evaluated for treatment choice and treatment outcome. Follow-up questionnaires were sent to dentists in cases where treatment outcome could not be determined from the radiographic material. Clinical evaluation was not possible as the patients were no longer associated with the clinic where they were treated. The cases were categorized into six groups: (A) no treatment; (B) orthodontic treatment; (C) surgical exposure of the second molar; (D) removal of the third molar; (E) removal of the second molar; and (F) other treatments. The various treatment choices performed during 1985-2005 showed acceptable results in 66 of the cases. In 23 cases, the results were unacceptable. In 37 cases, the radiographic material could not document the outcome nor was evaluation of the final outcome possible due to the patient's young age. Remarkable are the high percentages of unacceptable treatment outcome, 25.9% in group D (removal of third molar) and 23% in group E (removal of second molar). As the material was collected before new advanced methods of surgical uprighting and new methods of orthodontic uprighting had been introduced, these percentages are expectedly lower today. Even so, it is highly recommended to focus especially on these two groups in future studies on treatment outcome.

Apoptosis in the human periodontal membrane evaluated in primary and permanent teeth.

OBJECTIVE: Recent studies revealed a highly innervated layer in close proximity to the root surface in the periodontal membrane of human teeth. Persistence of the epithelial cells of Malassez along root surfaces without resorption has also been demonstrated. It is hypothesized that resorption is connected to apoptosis of the epithelial cells of Malassez. The purpose of this study is to localize cells undergoing apoptosis in the periodontal membrane of human primary and permanent teeth. MATERIALS AND METHODS: Human primary and permanent teeth were examined immunohistochemically for apoptosis and epithelial cells of Malassez in the periodontal membrane. All teeth examined were extracted in connection with treatment. RESULTS: Apoptosis was seen in close proximity to the root surface and within the epithelial cells of Malassez. This pattern of apoptotis is similar in the periodontal membrane in primary and permanent teeth. CONCLUSIONS: The inter-relationship between apoptotis and root resorption cannot be concluded from the present study. Apoptosis seen in close proximity to the root surface presumably corresponds to the highly innervated layer of the periodontal membrane. The function of this layer still needs to be elucidated.

Maxillary sagittal growth evaluated on dry skulls from children and adolescents.

OBJECTIVE: The hypothesis of the present study is that the inter-relationship between the greater palatine foramen (stable structure) and the first maxillary molar, which is located in the growing and forward-moving maxilla, expresses the longitudinal growth of the maxilla. MATERIALS AND METHODS: The material comprised 25 human anthropological maxillae, normally developed and without tooth agenesis. The material was sub-grouped according to dental stages. Each sample was photographed in the occlusal view and two transverse reference lines were constructed, one connecting the palatine foramina and another connecting the lingual interlobal incisions in the first permanent molars. The perpendicular distance (T) between these two lines expressed the distance between the foramen and the first molar. RESULTS: The T-distance increased markedly between the stages where the first, second and third molars had erupted. The study also showed that the greater palatine foramen was located palatally to the first molar in the stage where only the first molar had erupted, palatally to the second molar when this molar had erupted and palatally to the third molar when this molar had erupted. CONCLUSION: This study shows that the greater palatine foramen is located close to the most posterior located and erupted permanent molar in normally developed dentitions without agenesis. This information may be valuable for dentists when applying local anesthetics. Furthermore, the study revealed a growth pattern in the maxilla, which may reflect the etiology behind crowding in the maxillary molar region.

The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.

We described the morphology of the sella turcica in individuals with velocardiofacial syndrome (VCFS), also known as chromosome 22q11.2 deletion syndrome, and compared the morphology with that of a control group of individuals from the Oslo University Craniofacial Growth Archive. The aim was to measure the cranial base angles in individuals with VCFS and, if possible, to discover the developmental field that may be involved in the condition. The study included 33 patients with VCFS from the Copenhagen Cleft Palate Center, Denmark. The genotype was confirmed by fluorescence in situ hybridization. The morphology of the sella turcica was described and measurements of the cranial base angles were performed on lateral cephalometric radiographs. The VCFS individuals had larger deviations in the morphology of the sella turcica compared to individuals from the Oslo University Craniofacial Growth archive. The deviations were mostly in the posterior part of the dorsum sellae. Individuals with VCFS had increased cranial base angles. The results of this study combined with the information in the literature on the main defects in VCFS (palatal abnormalities, cardiac anomalies, thymic hypoplasia or aplasia, hypothyroidism, and posterior brain abnormality), suggest involvement of a specific developmental field.

Orthodontics and foetal pathology: a personal view on craniofacial patterning.

This article summarizes the essentials of studies on the craniofacial skeleton performed over 17 years. It presents data from research into foetal pathology resulting in new views on craniofacial patterning and/or fields for further discussion. The fields described cover all areas seen on profile, frontal, and panoramic radiographs. The fields are the theca, frontonasal, maxillary, palatine, and mandibular together with the cerebellar field and cervical spine. Regional fields in the dentition are described according to the pattern of peripheral nerve innervation. Studies on severely malformed foetuses show that the malformation can occur solely within a single field or in several fields. This is the background for these personal views on craniofacial patterning. These new views may assist in the diagnosis and interpretation of malformations in the cranium and dentition.

Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development.

Cleft lip and/or palate (CL/P) is a common congenital malformation with a complex etiology which is not fully elucidated yet. Epidemiological studies point to different etiologies in the cleft lip and palate subgroups, isolated cleft lip (CL), isolated cleft palate (CP) and combined cleft lip and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed. Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend that future gene expression in CL/P studies should use tissue from the correct embryonic time and place if possible, to overcome the biases in the presented study.

Cervical vertebrae, cranial base, and mandibular retrognathia in human triploid fetuses.

On profile radiographs of adults, an association between fusions of cervical vertebrae, deviations in the cranial base and mandibular retrognathia has been documented radiographically. An elaboration of this association on a histological level is needed. In human triploid fetuses severe mandibular retrognathia and deviations in the cranial base have previously been described radiographically (without cephalometry) and cervical column fusions radiographically as well as histologically. Therefore, triploid fetuses were chosen to elucidate the cranial base cephalomterically and histologically. In the present study, eight triploid fetuses were analyzed radiographically and histologically focusing especially on the cranial base, which borders to the spine and to which the jaws are attached. A histological analysis of the cranial base has not previously been performed in triploid cases. An enlarged cranial base angle and a retrognathic position of the mandible were documented cephalometrically on radiographs of all cases. Histologically, malformations were observed in the cranial base as well as in the spine. These are new findings indicating the association between the occipital bone and the uppermost vertebra in the body axis. As the notochord connects the cervical column and the cranial base in early prenatal life, molecular signaling from the notochord may in future studies support the notochord as the developmental link between abnormal development in the spine and the cranial base.

The morphology of the sella turcica in monozygotic twins.

The purpose was to compare the sella turcica morphology of individuals within pairs of monozygotic twins with normal karyotype and to analyze the similarity between the observed morphology and the morphology of non-twins at the same age with normal karyotype. Profile radiographs from 84 individuals of 42 twin pairs (18 male and 24 female pairs, aged 18-23 years) comprised the material. Sella turcica measurements from non-twins aged 6-21 years were used as normal reference. Length, depth and diameter of the sella turcica were measured and controlled by re-measurements. Pearson's correlation coefficient was used for comparison of individuals within twin pairs. For comparison of twins and non-twins, normal standard values for length, depth and diameter were subtracted from the twin values. For the mean values of these differences, confidence limits p values and t values were calculated. The study showed that the size of the sella turcica may be partly similar and partly dissimilar within the pair of monozygotic twins. Statistical evaluation of the data showed correlations between length, depth and diameter of the sella turcica between the two twin individuals in the same twin pair. Differences in sizes are observed between individuals in the twin material and individuals in the non-twin material. As a conclusion, the twin males were more similar within the twin pair, but deviated more from the non-twin material than the females. Female twins had more discrepancy within the twin pair, but deviated less from the non-twin material than the males.

The human periodontal membrane: focusing on the spatial interrelation between the epithelial layer of Malassez, fibers, and innervation.

OBJECTIVE: The purpose of the present study was to map the spatial interrelation of fibers, peripheral nerves, and epithelial layer of Malassez in human periodontal membrane in areas close to the root surfaces. MATERIAL AND METHODS: Four healthy permanent teeth extracted from four patients during puberty due to orthodontic treatment planning were analyzed. The extracted teeth, fixed in 4% neutral buffered formaldehyde for 5 days, were decalcified in 0.5 M EDTA. Paraffin blocks were sagittally cut in 5 microm thick serial sections and mounted on Superfrost Plus microscope slides. For survey, every fifth slide was stained with Alcian Blue/Van Gieson. Immunohistochemical reactions: Cytokeratin (wide spectrum screening) for epithelium, anti-vimentin for fibers, and anti-neuronal nuclei (NeuN) for innervation. RESULTS: The study indicates that the epithelial layer of Malassez is a border between different fiber morphologies and innervation patterns. Innervation is identified predominantly in the periodontal layer with tightly packed fibers close to the root surface. CONCLUSION: It is suggested that the genetic composition of the epithelial layer of Malassez in the periodontal membrane may be the key to understanding the different functions of the periodontal membrane and also the individual differences of these functions.

Lengths of the maxillary central incisor, the nasal bone, and the anterior cranial base in different skeletal malocclusions.

OBJECTIVE: Based on the results of previous studies of osseous structures within the frontonasal field in patients with a known malformation in the frontonasal field, the aim of the present study was to clarify whether the same structures were malformed in patients with severe skeletal malocclusions. MATERIAL AND METHODS: Incisor, nasal, and cranial base lengths were measured on lateral radiographs of adult patients with skeletal malocclusions, including open bite (n=35), mandibular overjet (n=56), maxillary overjet (n=31), deep bite (n=19), and compared with those of a control group with neutral occlusion and normal craniofacial morphology (n=39). Two-way ANOVA tests were used to evaluate differences in lengths between groups and gender. RESULTS: Statistically shorter maxillary central incisor length was found in the open bite group (p<0.05), the mandibular overjet group (p<0.001), and in the deep bite group (p<0.001) compared to the controls. Nasal bone length was shorter in the maxillary overjet group compared to controls (p<0.05). CONCLUSIONS: The lengths of the maxillary central incisor and nasal bone, both parameters located in the frontonasal field, are affected in different skeletal malocclusions. The present findings, especially the deviation of the upper incisor length in different skeletal malocclusions, are considered relevant for orthodontic diagnostics and treatment.

Immunohistochemical studies of the periodontal membrane in primary teeth.

OBJECTIVES: To describe the periodontal membrane of human primary teeth immunohistochemically, while focusing on the epithelial layer of Malassez, fibers, and peripheral nerves, and to compare the findings with those of a previous study of human permanent teeth. MATERIAL AND METHODS: Nineteen human primary teeth extracted in late childhood in connection with treatment were fixed, decalcified, dehydrated, and embedded in paraffin. Paraffin sections were stained with wide spectrum screening (WSS), Vimentin, and NeuN in order to mark the epithelial layer of Malassez, fibers, and peripheral nerves. RESULTS: For root surfaces without resorption, the epithelial rests of Malassez appeared as small scattered islands. The fibers varied from tightly packed close to the root surface to a messy and loose organization. Innervation could be seen in close proximity to the root surface. The epithelial cells of Malassez were not usually seen along root surfaces with resorption. The fibers were sparse or not present. Innervation was seen in close proximity to the root. In regions with repair of resorption lacunae, the immunohistochemical reactions for epithelial cells of Malassez, fibers, and innervation pattern could be identical to those in regions with no resorption. CONCLUSION: In regions without resorption, spatial organization of the periodontal membrane of primary teeth was similar to that of permanent teeth, although the number and distribution of epithelial cells and fibers differed. In regions with repair of root resorption, the epithelial cells of Malassez, fibers, and innervation appeared as root surfaces without resorption.