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.

[Ectoderm, mesoderm and neuroectoderm are tissue types of importance for understanding and preventing root resorption. Clinical guidelines]. / L'ectoderme, le mésoderme et le neurectoderme sont des types tissulaires importants pour la compréhension et la prévention des résorptions radiculaires. Recommandations cliniques.

INTRODUCTION: This three-part article summarizes ideas already described elsewhere by the author. Part 1. New way of diagnosing the dentition. For diagnostic purposes origin and appearance of the three tissue types - ectoderm, mesoderm (ectomesenchyme) and peripheral nerves - are depicted on orthopantomograms. Same tissue types are marked on the root surface (peri-root sheet). Part 2. Factors provoking root resorption. Resorption can be explained from the composition of the peri-root sheet. Deviations (inborn or acquired) in each of the three tissue layers can provoke inflammation, resulting in resorption. Orthodontic forces resulting in resorption can occur in normal peri-root sheets, but also in peri-root sheets with inborn deviations, important to diagnose. Part 3. How to prevent root resorption - Clinical guidelines. General diseases and different dental morphologies are signs predisposing for root resorption (ectoderm and mesoderm), so are local or general virus attacks (neuroectoderm). Resorption often occurs in dentitions never treated orthodontically. MATERIAL AND METHOD: The author performed a review of the literature in order to present a new diagnostic approach incorporating histological and embryological concepts. RESULTS: The review revealed different etiologies and sites involved in root resorption. Patients presenting variations of the peri-root sheet are most exposed to root resorption. DISCUSSION: At this stage, it is difficult to diagnose these variations. The author offers diagnostic recommendations to be followed prior to orthodontic treatment. Even when no orthodontic treatment is given, root resorption can occur unexpectedly. In these cases, resorption prevention is currently impossible.

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.

Mechanism of human tooth eruption: review article including a new theory for future studies on the eruption process.

Human eruption is a unique developmental process in the organism. The aetiology or the mechanism behind eruption has never been fully understood and the scientific literature in the field is extremely sparse. Human and animal tissues provide different possibilities for eruption analyses, briefly discussed in the introduction. Human studies, mainly clinical and radiological, have focused on normal eruption and gender differences. Why a tooth begins eruption and what enables it to move eruptively and later to end these eruptive movements is not known. Pathological eruption courses contribute to insight into the aetiology behind eruption. A new theory on the eruption mechanism is presented. Accordingly, the mechanism of eruption depends on the correlation between space in the eruption course, created by the crown follicle, eruption pressure triggered by innervation in the apical root membrane, and the ability of the periodontal ligament to adapt to eruptive movements. Animal studies and studies on normal and pathological eruption in humans can support and explain different aspects in the new theory. The eruption mechanism still needs elucidation and the paper recommends that future research on eruption keeps this new theory in mind. Understanding the aetiology of the eruption process is necessary for treating deviant eruption courses.

Dental anomalies in different cleft groups related to neural crest developmental fields contributes to the understanding of cleft aetiology.

OBJECTIVE: To analyze dental deviations in three cleft groups and relate findings to embryological neural crest fields (frontonasal, maxillary, and palatal). The overall purpose was to evaluate how fields are involved in different cleft types. DESIGN: Retrospective audit of clinical photographs, radiographs, dental casts, and medical records. PATIENTS: Ninety individuals (30 cleft lip, 30 cleft palate, and 30 combined cleft lip and palate), aged 5-27 years. MAIN OUTCOME MEASURES: Visual evaluation of tooth number and tooth morphology. RESULTS: Cleft lip: Dental deviations were predominantly observed in the frontonasal field. Supernumerary lateral incisors occurred significantly more often in cleft lip compared to other cleft types. Cleft palate: Dental deviations were observed in the maxillary and palatal fields indicating that both fields are involved in the development of cleft palate. Malformed roots were seen significantly more often in cleft palate. Combined cleft lip and palate: Number and type of dental deviations differed significantly from deviations in other cleft types, e.g. significantly more ageneses. CONCLUSIONS: Cleft lip seems to be caused by a disorder in neural crest migration to the frontonasal field and cleft palate by a disorder in neural crest migration to the maxillary and palatal fields. Combined cleft lip and palate seems to be caused by a primary early defect in the cranial course and function of the notochord. The dentition was significantly different in the different cleft types supporting the view of different aetiology/genetics.

Gender differences in patterns of second premolar agenesis observed in 4,756 individuals.

AIM: To elucidate intra- and inter-maxillary patterns of second premolar agenesis in the mandible and maxilla-including unilateral and/or bilateral occurrence and gender differences. STUDY DESIGN: The study comprised panoramic radiographs from 4,756 children with and without orthodontic treatment needs. METHODS: All radiographs were screened twice. 251 individuals had agenesis of one or more mandibular and/or maxillary second premolars; 37 had agenesis of both mandibular and maxillary second premolars. STATISTICS: Gender differences were analysed using χ² and Fisher's exact test. RESULTS: 193 individuals had agenesis of one or both mandibular second premolars, while 95 had agenesis of one or both maxillary second premolars. In females, agenesis of left and right second premolars was significantly associated in both the mandible and in maxilla (p < 0.0001). In males, this association was only significant in the maxilla (p < 0.0001). Bilateral agenesis occurred almost twice as frequently in females. Unilateral agenesis in the maxilla occurred almost twice as frequently in females. The probability of finding second premolar agenesis in the maxilla was significantly greater in females than in males (p = 0.03). A significant association was seen between agenesis of tooth 25 and 35 in females and males combined (p = 0.03) and in males alone (p = 0.01). No significance was found between agenesis of tooth 15 and 45 in either females or males. CONCLUSIONS: The study confirms some previous findings of second premolar agenesis and presents new observations on gender differences, especially concerning associations in agenesis occurrence within and between the jaws.

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.

Dental approach to craniofacial syndromes: how can developmental fields show us a new way to understand pathogenesis?

The paper consists of three parts. Part 1: Definition of Syndromes. Focus is given to craniofacial syndromes in which abnormal traits in the dentition are associated symptoms. In the last decade, research has concentrated on phenotype, genotype, growth, development, function, and treatment. Part 2: Syndromes before Birth. How can the initial malformation sites in these syndromes be studied and what can we learn from it? In this section, deviations observed in syndromes prenatally will be highlighted and compared to the normal human embryological craniofacial development. Specific focus will be given to developmental fields studied on animal tissue and transferred to human cranial development. Part 3: Developmental Fields Affected in Two Craniofacial Syndromes. Analysis of primary and permanent dentitions can determine whether a syndrome affects a single craniofacial field or several fields. This distinction is essential for insight into craniofacial syndromes. The dentition, thus, becomes central in diagnostics and evaluation of the pathogenesis. Developmental fields can explore and advance the concept of dental approaches to craniofacial syndromes. Discussion. As deviations in teeth persist and do not reorganize during growth and development, the dentition is considered useful for distinguishing between syndrome pathogenesis manifested in a single developmental field and in several fields.

Regional aggressive root resorption caused by neuronal virus infection.

During orthodontic treatment, root resorption can occur unexplainably. No clear distinction has been made between resorption located within specific regions and resorption occurring generally in the dentition. The purpose is to present cases with idiopathic (of unknown origin) root resorption occurring regionally. Two cases of female patients, 26 and 28 years old, referred with aggressive root resorption were investigated clinically and radiographically. Anamnestic information revealed severe virus diseases during childhood, meningitis in one case and whooping cough in the other. One of the patients was treated with dental implants. Virus spreading along nerve paths is a possible explanation for the unexpected resorptions. In both cases, the resorptions began cervically. The extent of the resorption processes in the dentition followed the virus infected nerve paths and the resorption process stopped when reaching regions that were innervated differently and not infected by virus. In one case, histological examination revealed multinuclear dentinoclasts. The pattern of resorption in the two cases indicates that innervation is a factor, which under normal conditions may protect the root surface against resorption. Therefore, the normal nerve pattern is important for diagnostics and for predicting the course of severe unexpected root 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.

Frontal sinus dimensions can differ significantly between individuals within a monozygotic twin pair, indicating environmental influence on sinus sizes.

CONCLUSION: The study showed that the size of the frontal sinus is not determined solely by genotype, but that other factors, e.g. environment, seem to affect the size as well. Environmental factors may include, for example diseases, trauma, allergies, acquired conditions, nutrition or medicine use. OBJECTIVES: The purpose of the study was to compare sinus dimensions between individuals within a monozygotic twin pair. METHODS: Profile radiographs were obtained from 42 pairs of monozygotic twins, 18 male and 24 female pairs (aged 18-23 years) with no known skeletal deviations in the cranium or general diseases. For each individual the size of the frontal sinus was analyzed on a profile radiograph and compared with the sinus size of the corresponding twin. The variation between twins was estimated using a random effects model for each gender. RESULTS: The sinus sizes varied considerably between twins. The standard deviation between female pairs was 2.98 mm and between male pairs 5.36 mm. The variations in sinus sizes between females and males within twin pairs were not significantly different (p = 0.86 for height and p = 0.83 for width, F test). Still, within one female twin pair and within two male twin pairs, sinus sizes varied significantly between the two individuals.

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.

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.

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.

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.

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.

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.