Generalized skeletal dysplasias (author's transl)

Skeletal Dysplasias are an important cause of short stature. Their overall frequency is unknown; their individual number exceeds 80. Prognostic and genetic counseling depend on a correct diagnosis of the specific bone dysplasia. Specific radiographic diagnoses are also needed for the meaningful interpretation of forthcoming histological, ultrastructural and biochemical studies which will help to elucidate the pathogenesis of skeletal dysplasias as prerequisite for a causal therapy.     

The cervical spine in the skeletal dysplasias and associated disorders

The cervical spine is an especially important area, not only for the diagnosis of the skeletal dysplasias, but also for the management of the patient. By the "cervical spine" I refer not only to the vertebral bodies and posterior elements of this region, but also to the neural elements contained within, especially the cervical cord. The spine is supported by a group of ligaments both anteriorly and posteriorly, with special fixation of the odontoid and C2 by a ligament which normally affixes it firmly to C1. Multiple things may go wrong with the development of the cervical spine. There may be abnormal development of the "vertebrae" in this region, ranging from hypoplasia to developmental failure and/or abnormal ossification of the cervical vertebrae; associated or unassociated odontoid hypoplasia; poor ligamental fixation of C2 resulting in C1-2 subluxation; abnormal development of the posterior processes; abnormal ligamental development or laxity with abnormal cervical kyphosis or lordosis; and, in the case of more fragile/brittle bone development (osteoporosis or increased bone density), fractures can lead to cervical spine problems. The skeletal dysplasias that involve cervical spine problems constitute about 35 of the 150 well-described disorders. These include certain families of disorders like the type II collagenopathies, as well as many individual disorders. It is very important for the clinician to be able to pilot patients through the various appropriate imaging modalities - conventional radiographs of the cervical spine; lateral flexion/extension views; CT; MRI - so that proper management and therapy will result.     

The long and the short of it: developmental genetics of the skeletal dysplasias

The skeletal dysplasias are a large heterogeneous group of genetic conditions characterized by abnormal shape, growth, or integrity of bones. Often, there may be prominent features associated with other organ systems as part of a more encompassing skeletal malformation syndrome. Tremendous advances have been made in the clinical and molecular delineation of these conditions over the past 20-30 years. We have progressed from initial broad clinical classifications of these conditions in the first two-thirds of this century, to extensive delineation based on radiographic features in the 1970s and 1980s, to the present reconsideration and grouping of these conditions according to their molecular pathogenesis. This has in part been spurred on by advances in the understanding of the developmental pathways which govern skeletal development, as well as by the human genome sequencing effort, which has provided a plethora of positional candidate genes for many of these conditions. The pathogenetic correlations derived from such studies are often based on parallels between the human phenotype and mouse models of the human condition, and have sometimes revealed novel developmental functions.     

Suspected skeletal dysplasias: femur length to abdominal circumference ratio can be used in ultrasonographic prediction of fetal outcome

OBJECTIVES: Skeletal dysplasias are a group of bone growth disorders, some of which can be recognized prenatally. Certain types of skeletal dysplasias result in a lethal fetal outcome. The ability to predict this outcome prenatally would be important in counseling parents. This study evaluated the ratio of femur length to abdominal circumference as a predictor of fetal outcome in cases of suspected skeletal dysplasia. STUDY DESIGN: This 3-year retrospective study identified 18 cases of prenatally suspected skeletal dysplasia from a population of approximately 35,000 fetuses undergoing prenatal ultrasonography. The femur length/abdominal circumference ratio was calculated and compared with fetal-neonatal outcomes and diagnoses. RESULTS: Eighteen cases of suspected skeletal dysplasia were identified, and the femur length/abdominal circumference ratio was found to be a good predictor of fetal outcome independent of gestational age. A ratio < 0.16 resulted in a lethal outcome in nine of nine cases. Conversely, a ratio > or = 0.16 resulted in a diagnosis of a nonlethal form of skeletal dysplasia or a diagnosis that ruled out any form of skeletal dysplasia in nine of nine cases. CONCLUSIONS: The femur length/abdominal circumference ratio may be useful to predict a lethal fetal outcome when ultrasonography indicates a possible skeletal dysplasia.     

Excitability changes and glucose metabolism in experimentally induced focal cortical dysplasias

Malformations of cortical development are increasingly recognized in association with severe epileptic syndromes, neuropsychological disorders and mental retardation. Several clinical and experimental studies suggest that functional consequences of cortical dysplasias are not restricted to the area of the dysplastic lesion but also involve remote brain regions. In the present study cortical malformations were induced in newborn rats at day of birth by intracerebral injection of the glutamatergic agonist ibotenate. The resulting cytoarchitectonic lesion associates neuronal depopulation of deep cortical layers, ectopic neurons in superficial layers and sulcus formation, mimicking human polymicrogyria and migration disorders. Electrophysiological recordings of evoked field potentials in slice preparations of adult animals reveal hyperexcitability in widespread cortical regions surrounding the dysplasia. Low-intensity stimulation induced epileptiform activity consisting of long-lasting, multiphasic and N-methyl-D-aspartate-dependent field responses. They appeared with high variability as all-or-none events. These widespread changes in excitability were not observed in sham-operated animals with small superficial ectopias but intact deep cortical layers, indicating that focal loss of these layers induces extended alterations in cortical connectivity and imbalance of excitation and inhibition. Restricted zones of increased excitability were also found in the forelimb and hindlimb representation cortex in sham-operated and control animals, demonstrating that this activity has to be considered as an intrinsic property of specific cortical areas. Deoxyglucose autoradiography showed that the widespread hyperexcitability in ibotenate-injected animals was not accompanied by alterations in glucose metabolism, although in the area of structural abnormality a typical metabolic pattern was found, revealing an increased glucose uptake in layer I. Hypometabolism as described for many types of human dysplastic lesions was not observed. This difference between the experimental and clinical data may be due to the absence of behavioral seizures in this model. However, it can be hypothesized that in patients with developmental malformations, additional pathogenic factors contribute to the manifestation of seizure disorders.     

Third and fourth cervical pouches remnants and branchial clefts

We present our experience with nine patients who were operated on for having cervical cysts lesions with the purpose of providing more information about this type of pathology. Five patients presented a left low-jaw cervical mass, diagnosed in the neonatal period. All of them presented with respiratory distress and in four of them quick local inflammatory manifestations appeared. A plain radiograph demonstrated liquid and air in the lesion and we proceeded to the operation. We made four drainages with marsupialization and in another patient complete excision of the lesion was made. Two marsupializations closed spontaneously and the other two had to be reoperated for excision of a pharyngo-cutaneous fistula. In the wall of the cyst there were thyroid-follicles, considering them remnants from the fourth branchial pouch. Three patients were diagnosed at one, two and five years of age respectively with a cervical mass and were operated on with complete excision. Due to its anatomic situation and lack of relation with other structures, we thought as probably deriving from the cervical sinus. In one patient who presented a mass in the inner side of the sternocleidomastoid muscle, complete excision of the lesion was made which had a tract joining the piriform sinus area, and thymic and thyroid tissue, being diagnosed as a cervical thymic cyst. All the patients cured with the complete excision. The anatomic situation ot these lesions and their connexions with next structures provide the best data to know their probable embrionary origin.     

Coronal microleakage in conservatively restored endodontic access preparations

The results of 122 hepatic resections in 112 patients with hepatocellular carcinoma are described. The type of liver resection performed was selected according to the patient's liver function. Forty-nine patients underwent anatomic resections, including 1 trisegmentectomy, 5 lobectomies, 11 segmentectomies, and 32 subsegmentectomies; the remaining 63 patients had nonanatomic resections. The 1-, 2-, and 3-year survivals after liver resection for all patients, taking into account one operative and one hospital death (0.9% each), were 92.4%, 85.0%, and 78.9%, and disease-free survivals at 1, 2, and 3 years were 68.6%, 46.2%, and 32.6%, respectively. Twenty-one repeat hepatic resections (17.2% of the total of 122 resections) were performed with no hospital mortality. Cumulative survival from the time of repeat hepatectomy in these 21 patients was 84.2% and 56.3% at 1 and 2 years, respectively. Among the factors that may affect survival or disease-free survival, the absence of vascular invasion (p < 0.05) and intrahepatic metastases (p < 0.01) were significantly related to the disease-free survival time. A good outcome was obtained after liver resection in 112 patients with hepatocellular carcinoma through appropriate choice of the type of resection, careful follow-up, and a vigorous surgical approach for recurrence.     

Argyrophilic proteins in the nucleolar organizer in the differential diagnosis of cervical dysplasias and cancer

Prospects of using the nucleolar organizer region (NOR) identification by silver nitrate for the diagnosis of dysplasias and cervical cancer were studied. Four groups of patients (22 cases) have been examined: group 1 (7 cases)--unchanged endocervical epithelium, group 2 (6 cases)--dysplasia of cervical epithelium of degree II-III, group 3 (3 cases)--carcinoma in situ, group 4 (6 cases)--invasive squamous cell nonkeratinizing carcinoma. The investigation showed that there are reliable differences in the quantity of silver granules per nucleus and also of NOR index between normal ectocervical epithelium and dysplasia, normal ectocervical epithelium and cancer, dysplasia and cervical cancer. The data obtained suggest that NOR argyrophilia may be a diagnostic marker of the tumor malignancy degree.     

Orofacial clefts in Hungary. Epidemiological and genetic data, primary prevention

The occurrences (birth prevalences) of different types of isolated and multiple orofacial clefts are known in Hungary. The empiric risk figures in the first-degree relatives of probands with cleft lip +/- cleft palate, cleft palate, Robin sequence and multiple congenital abnormalities including orofacial clefts as component defects were also determined. Finally the recent controversial data concerning the primary prevention of isolated orofacial clefts by periconceptional folic acid-containing multivitamins are summarized.     

Morphological changes of clefts in Plasmodium-infected erythrocytes under adverse conditions

Blood infected with human or rodent malaria parasites, Plasmodium falciparum or Plasmodium berghei, was exposed to higher pH, higher PO2, and lower temperature than those used in standard cultivation conditions. Parasitized blood was incubated for 20, 25, and 30 min with RPMI 1640 medium, 10% (vol/vol) serum, pH 8.0, at 20 degrees C in the air, conditions which are ultimately lethal to the asexual stages of malarial parasites. Markedly dilated clefts were observed in the cytoplasm of the malaria-infected erythrocytes so treated. These clefts can take up colloidal gold particles and macromolecules such as Protein A, rhodamine-dextran, and lucifer yellow-dextran. Such dilated clefts were not seen in the cytoplasm of infected erythrocytes that were incubated under normal cultivation conditions before fixation. These had slender clefts of the usual sort that did not take up colloidal gold particles and macromolecules.     

Endosseous implants for prosthetic rehabilitation in bone grafted alveolar clefts

The authors report their experience in the surgical and prosthetic rehabilitation of three patients affected by sequelae of cleft lip and palate, with residual alveolar cleft and absence of maxillary anterior teeth. The patients were treated by means of late secondary bone grafting of the alveolar cleft, followed by the insertion of endosseous titanium plasma-sprayed implants (IMZ). After a further healing period (6-12 months) fixed dental prostheses were constructed. Preliminary results from this series have shown how dental prostheses supported by endosseous implants in grafted alveolar clefts are a very reliable possibility in dental rehabilitation of this malformation.     

Two patients with multiple facial clefts including cleft lip and palate

Report of 2 patients with cleft lip and palate and multiple facial clefts are described using the anatomical classification of Tessier. The first patient was severely polymalformed, with heart, vertebral, and facial malformations. He was examined clinically and with an experimental three-dimensional computer reconstruction that identified an association of a classic cleft lip and palate with cleft nos. 4 and 11 on the right side and cleft nos. 3 and 11 on the left. The second patient, a partial form, with cleft lip and palate and cleft nos. 3 and 11 on the right side, also presented with bilateral cleft no. 7, preauricular tags, and an important microgenia. This second patient was operated for the cleft lip using the principles of Millard and Onizuka with a supplementary Z plasty. We comment on the difficulties of delimitation and treatment when the clefts are very close together and the difference in "quality" of the tissues compared with classic cleft lip and palate.     

Posterior sagittal anorectoplasty in the treatment of anorectal malformations

Posterior sagittal anorectoplasty is a marked change in treatment of anorectal malformations and differs fundamentally from previous techniques. In 1991-1996 86 patients (51 boys and 35 girls) aged 1 day to 22 years were operated. A primary operation was performed in 65 patients, a secondary one in 21 patients. In primary operations posterior sagittal anorectoplasty was used in 50 patients, in 3 cloacal malformations it was extended by reconstruction of the vagina and urethra. Fifteen patients were operated by other techniques. Posterior sagittal anorecto (vaginourethro) plasty was used in all 21 reoperated patients. Of 65 patients with primary operations one patient died from aspiration bronchopneumonia four years after operation. The patient had also an operation on account of oesophageal atresia. Three patients were reoperated. The continence of patients after primary operations is satisfactory, 5-6 points on Kelly's scale. In 19/21 reoperated patients the continence is 3-5 points according to Kelly. In two patients no substantial changes were recorded, one was reoperated twice. As compared with pull-through techniques the posterior surgical method of anorecto (vaginourethro) plasty is excellent. It cannot be used however without adequate experience.     

Ear manifestations in adolescents after closure of lip-jaw-palate- or isolated palatal clefts

We examined two groups of teenagers who had been surgically treated as small children for cleft palate. Most patients were between 13 and 21 years of age. One group had been looked after by the Dept. of Orthodontics at the University of Erlangen-Nürnberg, the other by the Dept. of Orthodontics at the University of Rostock. There were differences in sequence and time of the surgical closure between the two departments. Additionally, 60% of the people treated in Rostock had a velopharyngoplastic, which was rarely the case in Erlangen. In both groups only a few patients had been seen by an ENT-doctor regularly. Only some patients had been previously treated with tubes. There was one patient in each group with a bilateral, most likely genetically determined, sensorineural hearing loss. In Erlangen we examined 66 teenagers (132 ears). Six ears had been previously treated with one or more tympanoplasties. 10 ears needed further treatment due to a seromucotympanon, adhesions, perforations of the ear drum, suspicion of cholesteatoma or insufficient improvement of hearing after previous tympanoplasty. Another 18 ears showed signs of former inflammations. The control group in Rostock included 63 patients (i.e. 126 ears). 14 of the ears examined had undergone one or more tympanoplasties previously. 13 other ears needed further treatment for seromucotympanon, adhesions, perforations of the ear drum, insufficient improvement of hearing after tympanoplasty or cholesteatoma. Residuals due to prior inflammations were found in another 26 ears. Possible reasons for the different occurrence of middle ear problems in both groups are discussed.     

Coronal CT of the paranasal sinuses before and after functional endoscopic sinus surgery

Coronal CT of the paranasal sinuses and the ostiomeatal complex (OMC) was performed before and 12 months after bilateral functional endoscopic sinus surgery (FESS) in 30 patients with sinusitis and 12 patients with nasal polyposis. The extent of sinus mucosal thickening was graded, and the patency of the OMC was evaluated. After FESS, the percentage of open OMCs had increased from 42% to 83% in the sinusitis group, and from 8% to 45% in the polyposis group. There was only a small improvement in mucosal score in sinuses with opened OMC, so that the overall extent of sinus opacification before and after FESS was almost the same. Despite this, 91% of the patients reported clinical relief of symptoms. Preoperative coronal CT of the paranasal sinuses serves as an anatomical map for the surgeon, but there is no benefit of routine postoperative CT.