Inger Kjær

Pattern of malformations in the axial skeleton in human trisomy 18 fetuses

We examined and described the development and abnormalities of the axial skeleton in 10 human trisomy 18 fetuses. Whole-body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In 3 fetuses no spinal radiographs were available. Seven osseous regions or fields along the body axis were analyzed, four in the spine, and three in the cranial base and nasal bones. Malformations occurred in the occipital field in all fetuses. This was a characteristic notching, either unilateral or bilateral, of the basilar part of the occipital bone. Nasal bones were abnormal in 8 cases, either absent or hypoplastic. Malformations were found in the thoracic and/or lumbosacral field in 7 fetuses. A single abnormality was found in the cervical spine in one fetus. The pattern of axial skeletal malformation in trisomy 18 fetuses recorded in the present study has not been described previously. Axial skeletal radiography should be included in autopsies of fetuses when chromosome disorders are present or suspected. The methods applied here are unaffected by autolysis.

Human prenatal craniofacial development related to brain development under normal and pathologic conditions

A survey is given of current knowledge of the interrelationship between facial, cranial and brain development in humans. First, normal facial, cranial (mandible, maxilla, palatine bone, cranial base, theca cranii, dentition), and brain development are described separately. Then, developmental interrelationships are illustrated under normal and pathologic conditions (cleft lip and palate, holoprosencephaly, anencephaly, amniotic band sequence). New observations are described in detail, and references are given to previously published articles. A close interconnection exists between the development of the face, the craniofacial skeleton, and the brain. This is illustrated by new observations in cleft palate fetuses and new theories about the etiology of holoprosencephaly and tooth agenesis. The survey focuses, moreover, on the importance of the face and the cranial base in endocrine development. Borderlines between face regions and cranial regions with different developmental origin are set up for future elucidation of the etiology behind syndromes involving the craniofacial regions.

A histological and radiological investigation of the nasal bone in fetuses with Down syndrome

Previous studies of nasal bone development in Down syndrome have used radiographs or ultrasound for the detection of nasal bone length or nasal bone absence. The aim of this study was to investigate the presence and size of the nasal bones in postmortem Down syndrome fetuses by means of radiographs and histological examination.

Dental characteristics in Williams syndrome: a clinical and radiographic evaluation

Williams syndrome is a rare congenital syndrome with distinctive craniofacial features, cardiovascular abnormalities, and behavior characteristics including mental retardation. The dental abnormalities have received scant attention in previous literature. The aim of this study was to describe dental characteristics in individuals with Williams syndrome. In a group of 41 individuals more than 10 years of age, 40.5% had agenesis of one or more permanent teeth and 11.9% had agenesis of 6 permanent teeth or more. The mesio-distal and labio-lingual dimensions of permanent tooth crowns were measured on 31 dental study casts from individuals older than 12 years. The mesio-distal and labio-lingual dimensions were significantly smaller compared with a reference sample. An analysis of tooth morphology was performed on the same dental study casts revealing altered tooth morphology. A high proportion of maxillary and mandibular incisors was tapered or screwdriver shaped. An evaluation of taurodontism on mandibular permanent molars was performed using a metric crown-body/root ratio. However, most of the molars rated as being taurodontic had short or extremely short total tooth lengths and could thus be rated taurodontic without meeting the classical definition. The results of this study indicate that although there is variation in dental development in individuals with Williams syndrome, agenesis of permanent teeth in combination with aberrations in tooth size and morphology may affect dental esthetics and complicate orthodontic and prosthodontic treatment.

An immunocytochemical study of the innervation of developing human fetal teeth using protein gene product 9.5 (PGP 9.5)

Developing teeth of 32 human fetuses (crown-rump length 11-205 mm) were examined immunohistochemically by antisera to protein gene product 9.5 (PGP 9.5) in an attempt to shed light upon the possible role of innervation in odontogenesis. As a control for the specificity of PGP 9.5 as a neuronal marker, the results were verified by immunocytochemical co-localization in peripheral nerves of neurone-specific enolase, neurofilaments and S-100 protein. The dental follicle received the first nerve fibres in the early cap stage. At this stage, fibroblasts differentiated in the presence of nerve fibres and formed the dental follicle surrounding the developing tooth. In the dental papilla, however, no fibres were demonstrated until the dentine and enamel matrices had formed, about half of the present height of the tooth germ. Most nerve fibres were localized in the basal part of the papilla until the last stage examined and usually followed the blood vessels of the papilla. Thus the effect of innervation on tooth development may be associated with the development of the dental follicle. A novel finding was that functional odontoblasts were not only positive for S-100 but also for PGP 9.5, indicating their neural crest origin.

Cervical column morphology in patients with skeletal open bite

OBJECTIVES To examine and compare the cervical column morphology in adult patients with skeletal open bite with the cervical column morphology of an adult control group with neutral occlusion and normal craniofacial morphology. DESIGN A retrospective case-control study. SETTING AND SAMPLE POPULATION Thirty-eight open bite patients, 27 women, aged 17-39 years, and 11 males, aged 18-40 years were compared with 21 controls, 15 females, aged 23-40 years, and six males aged 25-44 years from profile radiographs. OUTCOME MEASURE From each individual a visual assessment of the cervical column and angular measurements of the craniofacial dimensions were performed on profile radiographs. RESULTS In the open bite group 42.1% had cervical column body fusion, and 13.2% had posterior arch deficiency. The fusion always occurred between C2 and C3. Cervical column deviations occurred significantly more often in the open bite group compared with the control group (p < 0.05). Associations were found between fusions of the cervical column and maxillary retrognathia (p < 0.05), large maxillary inclination (p < 0.05) and large cranial base angle (p < 0.05). Associations were also found between posterior arch deficiency and maxillary retrognathia (p < 0.05) and cranial base angle (p < 0.05). The craniofacial parameter most important for the fusions and posterior arch deficiency was the maxillary retrognathia (p < 0.01, R (2) = 0.20; p < 0.05, R (2) = 0.26, respectively). CONCLUSION - New associations between skeletal open bite and cervical column deviations are described. It is suggested that this knowledge is incorporated in future diagnostic and orthodontic treatment planning.

Prenatal Development of the Normal Human Vertebral Corpora in Different Segments of the Spine

Study Design. Vertebral columns from 13 normal human fetuses (10‐24 weeks of gestation) that had aborted spontaneously were investigated as part of the legal autopsy procedure. The investigation included spinal cord analysis. Objectives. To analyze the formation of the normal human vertebral corpora along the spine, including the early location and disappearance of the notochord. Summary of Background Data. Reference material on the development of the normal human vertebral corpora is needed for interpretation of published observations on prenatal malformations in the spine, which include observations of various types of malformation (anencephaly, spina bifida) and various genotypes (trisomy 18, 21 and 13, as well as triploidy). Methods. The vertebral columns were studied by using radiography (Faxitron X‐ray apparatus, Faxitron Model 43855, Hewlett Packard) in lateral, frontal, and axial views and histology (decalcification, followed by toluidine blue and alcian blue staining) in and axial view. Immunohistochemical marking with Keratin Wide Spectrum also was done. Results. Notochordal tissue (positive on marking with Keratin Wide Spectrum [DAKO, Denmark]) was located anterior to the cartilaginous body center in the youngest fetuses. The process of disintegration of the notochord and the morphology of the osseous vertebral corpora in the lumbosacral, thoracic, and cervical segments are described. Marked differences appeared in axial views, which were verified on horizontal histologic sections. Also, the increase in size was different in the different segments, being most pronounced in the thoracic and upper lumbar bodies. The lower thoracic bodies were the first to ossify. The morphologic changes observed by radiography were verified histologically. Conclusions. In this study, normal prenatal standards were established for the early development of the vertebral column. These standards can be used in the future‐for evaluation of pathologic deviations in the human vertebral column in the second trimester.

Anomalies of the cervical vertebrae in patients with skeletal Class II malocclusion and horizontal maxillary overjet.

INTRODUCTION Cervical column morphology was examined in adult patients with skeletal Class II malocclusion and horizontal maxillary overjet; the findings were compared with cervical column morphology in an adult control group with neutral occlusion and normal craniofacial morphology. This has not previously been investigated. METHODS The overjet group consisted of 34 patients: 28 women (ages, 18-42 years) and 6 men (ages, 18-38 years). Their horizontal overjets ranged from 5.47 to 15.29 mm. The control group consisted of 21 subjects: 15 women (ages, 23-40 years) and 6 men (ages, 25-44 years). A visual assessment of the cervical column was made, and craniofacial dimensions were measured on each subjects profile radiograph. RESULTS In the overjet group, 52.9% had fusion of the cervical column, and 5.9% had posterior arch deficiency. Fusions occurred significantly more often in the overjet group compared with the control group (P <.01). Associations were found between fusions of the cervical column and mandibular retrognathia (P <.05), large cranial base angle (P <.05), and large horizontal overjet (P <.05). CONCLUSIONS The results could provide a new method to phenotypically subdivide skeletal maxillary overjets. This is important for the diagnosis and the correct treatment of these patients.

Pituitary gland and sella turcica in human trisomy 21 fetuses related to axial skeletal development

The purpose of the present investigation was to study the sella turcica/pituitary gland region in trisomy 21 fetuses and to relate the findings in the region to the ossification pattern in the axial skeleton formed by the cranial base and spine. Material from 22 human fetuses with trisomy 21, CRL 80 mm to CRL 190 mm, corresponding to gestational ages from 14 to 21 weeks, was examined and compared with material from gestation-matched normal controls. After radiography, tissue blocks from the cranial base, including the pituitary gland, were examined and compared with those of normal fetuses. Four different types of sella turcica/ pituitary gland morphology were observed. Thirteen fetuses (Type I) were morphologically normal. Minor abnormalities occurred in the sella turcica and pituitary gland (adenopituitary gland tissue pharyngeally) in six fetuses (Types II and III). There was agreement between the histologically recorded deviations in the sella turcica and the radiographic observations of the basisphenoid bone. In three cases (Type IV) out of 22, more pronounced structural abnormalities occurred in the sella turcica, and radiographically the basisphenoid bone appeared cleft. All sella turcica changes observed in trisomy 21 were situated anteriorly in the base of the sella. In all cases the basilar part of the occipital bone was normal. Minor changes in the sella turcica region were mainly accompanied by cervical vertebral abnormalities, while the most severe abnormalities occurred in association with malformations in the lumbar vertebrae. There was no association between sella turcica malformations and the absence or presence of the nasal bone.

Postnatal structure of the sella turcica in Down syndrome

The purpose of this study was to analyze the shape of the sella turcica in a group of patients with Down syndrome and compare the findings with those made earlier in human fetuses with Down syndrome. Profile radiographs from 78 patients (age 4 months to 50 3/12 years) were analyzed. A tracing was made of each sella turcica, and the shape was compared with that of a normal sella, including the normal growth pattern from childhood to adulthood. Sella turcica structure could be classified into three morphological types, defined as: type I, almost normal appearance; type II, deviations in the anterior wall; and type III, deviations in the floor of the sella turcica. Compared with previously registered prenatal structural deviations in the sella turcica, it can be concluded that the postnatal radiographic material reflects the prenatal findings, because type I, both prenatally and postnatally, is by far the most common, whereas the remaining types are uncommon, both prenatally and postnatally. The study confirms the relevance of prenatal investigations for postnatal diagnostics as previously documented in sella turcica analyses of prenatal and postnatal myelomeningocele cases.