[Anomalies of the skull in cleidocranial dysplasia]. / Schädelanomalien bei Dysostosis cleidocranialis. Eine HNO-ärztliche und kraniofaziale Röntgenstudie.

BACKGROUND: The description of the otorhinolaryngeal and craniofacial anomalies in patients with cleidocranial dysplasia. METHODS: For this study, 26 patients with cleidocranial dysplasia were examined after their medical history had been recorded. The main focus was placed on otorhinolaryngological and orthodontic findings. RESULTS: The portion of spontaneous mutations in our patient population was 46.1%. All patients exhibited otorhinolaryngological and craniofacial anomalies. While single ENT-anomalies were expressed in 76.9%-92.3% of the patients, the craniofacial findings were distributed over 84.6%-92.3%. CONCLUSION: The expression of this rare disorder is variable and its symptomatology not always distinct. Otorhinolaryngological and craniofacial anomalies are often apparent. Appropriate treatment can significantly contribute to an improvement in the patient's quality of life. In cases of ambiguous findings, we recommend consultation with an experienced clinician as well as genetic counselling.

Pressure simulation of orthodontic force in osteoblasts: a pilot study.

OBJECTIVES: To elucidate the RUNX2 gene expression induction in human osteoblasts after mechanical loading. DESIGN: Using a stringent pulse-chase protocol human osteoblasts were exposed to centrifugal pressure force for 30 and 90 min. Untreated control cells were processed in parallel. Before, and at defined times after centrifugation, total RNA was isolated. RUNX2 gene expression was measured using real-time quantitative reverse transcriptase polymerase chain reaction. The stress/control ratio was used to illustrate possible stimulatory or diminishing effects of force application. RESULTS: Immediately after 30 min of force application the RUNX2 gene expression was induced by a factor of 1.7 +/- 0.14 as compared with the negative control. This induction decreased rapidly and reached its pre-load levels within 30 min. Longer force applications (up to 90 min) did not change the RUNX2 gene expression. CONCLUSION: In mature osteoblasts centrifugal pressure force stimulates RUNX2 gene expression within a narrow time frame: loading of mature cells results in a temporary increase of RUNX2 expression and a fast downregulation back to its pre-load expression level. With this pilot study the gene expression behavior after mechanical stimuli could be determined with a simple laboratory setup.

Early craniofacial signs of cleidocranial dysplasia.

OBJECTIVES: Early diagnosis of CCD is essential for a timely introduction of the appropriate treatment approach. Since certain symptoms first fully manifest only during the pubertal growth spurt, their indicatory signs are often overlooked. The aim of this study is to describe the initial craniofacial findings in patients with CCD in order to categorise their reliability for early detection. METHOD: 14 patients with CCD between the ages of 6 and 11 years who were referred to the University of Regensburg over a 4-year period were included in this study. The patients were examined clinically and radiologically and their dental status was determined. Typical signs of CCD were analysed according to such classic criteria as the 'quatermoon'-physiognomy described in the literature. The clinical findings were compared to medical data and case history. RESULTS: Early signs were registered for each patient. While some signs could be found in all patients, others were variably expressed. The typical extraoral symptoms were only rarely exhibited in our patient population. CONCLUSION: As various indicators of CCD are age related, their expression should be taken into account for early diagnosis. Apparent signs only manifest during the growth spurt when the ideal timeframe for beginning treatment has already past. The symptoms described should serve as early markers to aid the general and paediatric dentist in planning appropriate treatment or referring patients to specialised centres.

[Symptoms and signs in cleidocranial dysplasia (CCD)]. / Symptome und Merkmale bei Dysostosis Cleidocranialis (DCC).

AIM: Occurrence of main symptoms and the rate of spontaneous mutations in patients with cleidocranial dysplasia. METHOD: 24 patients with variable phenotypic expression of CCD were examined symptomatically. The main focus was placed on findings in the shoulder girdle, craniofacial symptoms and alterations in radiologic opacity. RESULTS: The average age of the patients was 18.3 years. In our patient cohort, 58.3% were spontaneous mutations. Abnormal apposition of the shoulders were found in 88% of the patients. Craniofacial symptoms were diagnosed in 88%. An increase of the radiologic skull density was apparent in 95%. CONCLUSION: The expression of this rare disorder is variable and its symptomatology not always apparent. Spontaneous mutations occur frequently. Due to the high prevalence of the considered symptoms, the diagnosing physician should focus on the facial appearance and shoulder abnormalities. In cases of ambiguous findings we recommend a consultation of an experienced clinician as well as genetic counseling.

Dentomaxillofacial variability of cleidocranial dysplasia: clinicoradiological presentation and systematic review.

OBJECTIVES: The aim of this study was to determine the clinical and radiological presentation of cleidocranial dysplasia (CCD) in our patient group and to compare them with other reported cases by a systematic review (SR) of the literature. METHODS: The study comprises two elements, a complete series of all diagnosed patients at the Center for Craniofacial Genetics at the University of Regensburg, Germany, and a SR. Relevant literature was identified by electronic databases, review of citation lists and hand searching of key journals. The principal selection criterion was that the study should contain as many pertinent cases as possible. The presented signs and symptoms were assigned to the following categories: "supernumerary teeth", "failure of eruption", "hypoplastic maxilla" and "clavicular sign". Additionally, the family history was taken into account. RESULTS: From the 410 English, German or French articles, 40 single case presentations and 17 multiple case studies remained that met the selection criteria. This report reviews the data of 283 patients with CCD including our own patient cohort of 24 individuals. Dental signs such as supernumerary teeth and eruption failure were expressed in over 93.5%. Skeletal symptoms such as hypoplastic maxilla and the clavicular sign were exhibited in over 84.3%. The prevalence of spontaneous mutations differs slightly when comparing the single case studies (72.0%) with our patient data (58.3%). The fraction of spontaneous mutations in multiple case studies was 5.0%. CONCLUSION: The diagnosis of CCD can be difficult when typical features are not clearly expressed. Since the multiple case studies concentrated on specific clinical aspects, an overall ranking including all associated findings was not possible. Owing to their prevalence, we recommend referencing to the described list of clinical signs as major symptoms for the pathognomy in CCD, since they are infrequent in other conditions and in the general population. To categorize the expression of CCD, more interdisciplinary studies are necessary. Nevertheless, a subjective classification is possible according to the related restrictions in the patients' quality of life.

[Inter- and intrafamilial expression of cleidocranial dysostosis]. / L'expressivité inter- et intrafamiliale de la dysostose cléido-crânienne.

Cleidocranial dysplasia is a bony autosomal dominant disorder, defined by late closure of fontanels and sutures, clavicular aplasia or hypoplasia and supernumerary teeth. The aim of our study was to define the CBFA1 mutations in three families with cleidocranial dysplasia and to describe the phenotype expression within and between the families. While the mutation R225Q caused a similar phenotype within one family, the mutation G146R, located in the same domain, was the cause of a variable expression between two family members. A third mutation, R190Q was responsible for symptoms not commonly associated with this disorder. The results of our craniofacial examination are in agreement with the numerous descriptions in the literature. This study accents the difficulty in establishing a clinical based diagnosis due to the wide variability.

Atypical expression of cleidocranial dysplasia: clinical and molecular-genetic analysis.

Cleidocranial dysplasia (CCD) and the Rubinstein-Taybi syndrome (RTS) are two rare congenital syndromes that have many clinical signs in common. We present an 18-year-old-patient with untypical CCD expression who was misdiagnosed with RTS at the age of 2 years. An extensive craniofacial examination was carried out with respect to morphological and dental aspects. The molecular-genetic analysis of two underlying genes (CBFA1 and CBP) for CCD and RTS was performed using SSCP, direct sequencing and FISH. While the clinical examination showed uncharacteristic CCD symptoms with some findings common for RTS, the molecular-genetic analysis revealed a missense mutation in the CBFA1 gene, which is considered to be the etiological factor for CCD. Our findings with this patient presented clear evidence for the wide morphologic variety that can be related to a certain gene such as CBFA1. The diagnosis of rare diseases is currently based on the clinical phenomenology of small groups or single cases. The use of molecular-genetic biology extends the horizon of diagnostic and scientific possibilities. In this patient, it allowed us to compare the clinically diagnosis to molecular-genetic data. We conclude that molecular-genetic analysis may be a helpful tool in the differential diagnosis of many congenital diseases such as CCD and RTS.

The recording of monophasic action potentials with fractal-coated iridium electrodes in humans.

The present study was designed to evaluate the feasibility of the recording of monophasic action potentials (MAP) with fractal-coated iridium electrodes in a clinical setting. In 18 patients who underwent an electrophysiological study for various arrhythmias, we performed MAP recordings with both 1.3-mm2 and 6-mm2 tip surface area fractal-coated iridium and standard silver--silver chloride (Ag/AgCl) electrodes in the high right atrium and two ventricular positions. Amplitude and MAP duration at 90%, 50%, and 25% of repolarization were calculated during steady-state pacing at 600, 500, and 400 ms cycle lengths with extrastimuli application. Morphology comparisons of MAP signals recorded with both types of electrodes were performed by regression analysis using 5% of the repolarization segments of the MAP trajectory. Differences between MAP duration at 90%, 50%, and 25% of repolarization recorded with fractal-coated and Ag/AgCl electrodes were statistically insignificant. Amplitude values recorded with 6-mm2 tip electrodes were significantly smaller than those recorded with Ag/AgCl electrodes for all comparisons. During steady-state pacing, the correlation coefficients between Ag/AgCl and fractal-coated 1.3-mm2 and 6-mm2 tip electrodes were within the range of 0.93-0.999 and 0.87-0.999, respectively. The correlation of MAP amplitude and duration at 90%, 50%, and 25% of repolarization following the extrastimulus S2, recorded with both types of electrodes, was significantly weaker for right atrial recordings (r value range 0.78-0.92) as compared to ventricular recordings (r value range 0.92-0.99). The MAP sensing features of fractal-coated iridium and Ag/AgCl electrodes are comparable. The best results for recording of MAPs with fractal-coated electrodes can be achieved with small surface area tip electrodes.

A novel missense mutation of the CBFA1 gene in a family with cleidocranial dysplasia (CCD) and variable expressivity.

The aim of this study was to analyze the CBFA1 gene in a phenotypically variable family with autosomal dominant cleidocranial dysplasia (CCD). Five members of a family with CCD were characterized clinically. X-rays and photographs of the two clinically affected family members were taken. The genotype of all five affected family members was determined with the use of single strand conformation polymorphism (SSCP) and direct sequencing. A point-mutation in exon 2 (R148G) was detected in a patient with the full-blown clinical phenotype. His son, demonstrating the same mutation, showed only the dental CCD characteristics. No mutation could be found in the three clinically healthy family members. To conclude, a missense mutation in the CBFA1 gene was detected in a family with variably expressed CCD syndrome. A detailed clinical examination is necessary to detect minimally affected gene mutation carriers.

Intraoperative recordings of monophasic action potentials with chronically implantable pacemaker leads.

Since the development of fractally coated Iridium electrodes recordings of monophasic action potentials are possible. Intraoperative recordings of MAP from 15 pacemaker implantations were done after positioning the chronically implantable pacemaker leads (Biotronik, Berlin, Germany) in the right ventricle by using five screw-in electrodes and ten anchor electrodes. Intraoperative recordings of MAP are possible with all implanted pacemaker leads. The recordings of typical MAP signals were always accompanied with stable electrode positions and good sensing and pacing characteristics.

Influence of facial growth pattern on outcome of extraction therapy.

The present clinical-radiological study analyzes orthodontic casts and lateral cephalometric X-rays (at start and finish of orthodontic treatment) of 56 extraction cases, most of them adolescent patients who had 4 teeth extracted. The test group was classified into 3 morphological categories according to growth patterns. For comparison purposes, cephalometric findings of morphologically matching non-extraction groups as well as corresponding data from the literature were used. There was no deepening of overbite in any of the extraction cases in the different test groups. However, an average bite opening of 1.2 mm was found in patients with a neutral or horizontal growth pattern. Irrespective of the growth pattern, a significant increase in anterior and posterior facial height as well as a mean reduction of the ANB angle between 0.9 degrees and 1.3 degrees was found in the different extraction groups. These results matched those of the corresponding nonextraction control groups. At the end of treatment, the longitudinal axis of the upper incisors appeared too steep (retruded). Overall, the individual growth pattern was found to be of very little relevance to treatment results, provided a well considered treatment plan had been drawn up.

[Velopharyngeal closure in adolescents after repair of cleft lip, jaw, palate or isolated cleft palate]. / Velopharyngealer Abschluss bei Jugendlichen nach Verschluss einer Lippen-Kiefer-Gaumen- oder isolierten Gaumenspalte.

We examined two groups of teenagers (between 13 and 21 years of age) who had been surgically treated as small children for congenital cheilognathouranoschisis or cleft palate. A group of 62 teenagers had been treated by the Dept. of Orthodontics at the University of Erlangen-Nuremberg, the other group of 61 by the Dept. of Orthodontics at the University of Rostock. There were differences between the two departments in sequence and time of the surgical closure as well as in the frequence of velopharyngoplasties. The velopharyngeal closure was examined in all patients by means of a flexible fibre endoscope which was pushed forward endonasally up to the choanae. Simultaneously we judged the audibility of the nasal perflation while pronouncing /k/. A residual gap during articulation of /k/ with clearly audible or alternately clearly and discreetly audible nasal perflation was noted in 8 subjects in Erlangen and 14 subjects in Rostock. In subjects whose velum moved only anterior-posteriorly, closure was likely to be less good than in those with a circular closing mechanism of velum and lateral and/or posterior parts of the pharyngeal musculature. In rare cases we found a good velopharyngeal closure in spite of a large gap between the velum and the posterior pharyngeal wall at rest. This was the case when the velum moved more against the upper than the posterior wall of the nasopharynx. Velopharynxplasty did not reduce nasal airflow in case of insufficient function of the velar muscles. Differences in the mode of velopharyngeal closure might be due to statistically significant regional differences in skull structure.(ABSTRACT TRUNCATED AT 250 WORDS)

[The diagnosis and treatment of congenital facial asymmetries in childhood. A clinical study]. / Diagnostik und Behandlung von angeborenen Gesichtsasymmetrien im Kindesalter. Eine klinische Studie.

Following a brief discussion of etiology, pathogenesis, and diagnosis of congenital facial asymmetries, a new interdisciplinary treatment concept encompassing the disciplines of orthodontics, maxillo-facial surgery, and pedaudiology is set forth. This concept calls for the surgical reconstruction of the mandibular ramus and of the temporo-mandibular joint already in childhood in those cases in which functional jaw orthopedics has already begun at an early age. Thereafter the occlusal plane can be corrected orthodontically. Six patients were treated according to this concept. Two years nine months after surgery favorable results were observed in relation to occlusion and mandibular growth. Because, however, long term results are still outstanding, the results obtained until now and the treatment concept remain the subject of ongoing critical study.

[Reconstruction of the lateral face in children]. / Die Rekonstruktion des lateralen Gesichtes bei Kindern.

Unilateral hypoplasia in the middle and lower face has different etiological causes. A standardized interdisciplinary treatment of children is demonstrated with the help of ten operated cases and nine children in observation. Depending on the missing structure of the anatomical regions the areas are reconstructed. A pre- and postoperative orthodontic treatment is part of the concept. With an operative intervention in childhood, it is possible to gain in most cases a more normal appearance till adulthood.

[Ear manifestations in adolescents after closure of lip-jaw-palate- or isolated palatal clefts]. / Ohrbefunde bei Jugendlichen nach Verschluss einer Lippen-Kiefer-Gaumen- oder isolierten Gaumenspalte.

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.

[The quality of velopharyngeal closure in relation to facial morphology in CLP patients]. / Die Qualität des velopharyngealen Abschlusses in Abhängigkeit von der Gesichtsmorphologie bei LKG-Spalten.

Employing nasal endoscopy a follow-up study of 59 adult CLP-patients was conducted for the purpose of investigating velopharyngeal functions both during swallowing and during phonation of the letter "K". The results were subsequently compared with cephalometric values. In relation to phonation, the velopharyngeal activity could be subdivided into two groups, one demonstrating predominantly circular muscular activity and the other velar muscular activity. Both groups exhibited differing but, overall, a high quality of velopharyngeal closure. When swallowing all patients experienced complete velopharyngeal closure. It was striking to note, however, the slight muscular activity of the Passavant ridge during both swallowing and phonation. Significant relations were found to be present between facial morphology and velopharyngeal functions in terms of inclination of both the basis of maxilla and the mid-basicranium.

[Sonography--a diagnostic tool for the dynamic functional analysis of the tongue]. / Die Sonographie--ein diagnostisches Mittel zur dynamischen Funktionsanalyse der Zunge.

The possibility of using ultrasonography to analyse tongue function in the orthodontic setting was investigated in a pilot study involving ten dental students and ten adult, former patients with cleft, lip, jaw and palate. The ultrasonograms were videotaped and the contour of the tongue at rest and during swallowing was analysed in an extremely slow-motion playback mode. Ultrasonography was capable of clearly showing differences in tongue function between both groups. Ultrasonography may therefore be considered a useful technique for visualisation of individual tongue movements. In orthodontics, ultrasonography could be extremely helpful for the long-term documentation of myofunctional treatment, craniofacial anomalies, or in epidemiological research. Standard conditions for investigation and analysis of results still have to be elaborated.