Angelika Stellzig-Eisenhauer

PTHR1 Loss-of-Function Mutations in Familial, Nonsyndromic Primary Failure of Tooth Eruption

Tooth eruption is a complex developmental process requiring coordinated navigation through alveolar bone and oral epithelium. Primary failure of tooth eruption (PFE) is associated with several syndromes primarily affecting skeletal development, but it is also known as a nonsyndromic autosomal-dominant condition. Teeth in the posterior quadrants of the upper and lower jaw are preferentially affected and usually result in an open bite extending from anterior to posterior. In this study, we show that familial, nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor for parathyroid hormone and parathyroid hormone-like hormone (PTHR1). Three distinct mutations, namely c.1050-3C > G, c.543+1G > A, and c.463G > T, were identified in 15 affected individuals from four multiplex pedigrees. All mutations truncate the mature protein and therefore should lead to a functionless receptor, strongly suggesting that haplo-insufficiency of PTHR1 is the underlying cause of nonsyndromic PFE. Although complete inactivation of PTHR1 is known to underlie the autosomal-recessive Blomstrand osteochondrodysplasia (BOCD), a lethal form of short-limbed dwarfism, our data now imply that dominantly acting PTHR1 mutations that lead to haplo-insufficiency of the receptor result in a nonsyndromic phenotype affecting tooth development with high penetrance and variable expressivity.

Impact of facial asymmetry in visual perception: A 3-dimensional data analysis

INTRODUCTION The aim of this controlled study was to analyze the degree and localization of 3-dimensional (3D) facial asymmetry in adult patients with cleft lip and palate (CLP) compared with a control group and its impact on the visual perception of faces. METHODS The degree of 3D asymmetry was analyzed with a novel method without landmarks in 18 adults with complete unilateral CLP and 18 adults without congenital anomalies. Furthermore, the CLP and control faces were rated for appearance, symmetry, and facial expression by 30 participants. RESULTS The results showed that adults with CLP had significantly greater asymmetry in their facial soft tissues compared with the control group. Moreover, the lower face, and particularly the midface, had greater asymmetry in the CLP patients. The perceptual ratings showed that adults with CLP were judged much more negatively than those in the control group. CONCLUSIONS With sophisticated 3D analysis, the real morphology of a face can be calculated and asymmetric regions precisely identified. The greatest asymmetry in CLP patients is in the midface. These results underline the importance of symmetry in the perception of faces. In general, the greater the facial asymmetry near the midline of the face, the more negative the evaluation of the face in direct face-to-face interactions.

Reliability of a Method for Computing Facial Symmetry Plane and Degree of Asymmetry Based on 3D-data.

Objective:The objective of this study was to analyze the reliability of a landmark-independent method for determining the facial symmetry plane and degree of asymmetry based on three-dimensional data from the facial surface from two sets of recordings, one performed consecutively and one performed on different days.Materials and Methods:We used an optical 3D-sensor to obtain the facial data of one male subject in two sets of ten measurements: the first taken consecutively and the second on different days. The symmetry plane and degree of asymmetry were calculated for each of the resulting twenty sets of data. One set of data was analyzed ten times for control purposes. The calculation of the mean deviation angle between the symmetry planes served as a measure of the reproducibility of these results.Results:Although the mean angular deviations of the computed symmetry planes, 0.134° (for ten consecutively captured images) and 0.177° (for the ten images captured on different days), were each significantly higher than the mean angular deviation (0.028°) calculated from ten analyses of a single image, they can still be regarded as very small. There were no significant differences in the degree of asymmetry among the three measurement sets. The standard deviations revealed low values.Conclusions:This method can be used to compute with high reliability the symmetry planes and degree of asymmetry of facial 3D-data. The color-coded visualization of asymmetrical facial regions makes it possible for this analytical procedure to capture the asymmetries of facial soft tissue with substantially greater precision than 2-dimensional en face images.ZusammenfassungZielsetzung:Ziel der vorliegenden Untersuchung war es, die Reliabilität einer landmarkenunabhängigen Methode zur Berechnung der Gesichtssymmetrieebene und des Asymmetriegrades bei aufeinanderfolgenden beziehungsweise an verschiedenen Tagen durchgeführten 3-D-Aufnahmen zu analysieren.Material und Methodik:Die 3-D-Gesichtsdaten eines männlichen Probanden wurden mit einem optischen Sensor erfasst. Es wurden zehn Aufnahmen direkt nacheinander sowie an verschiedenen Tagen durchgeführt, für welche jeweils die Symmetrieebene und der Asymmetriegrad berechnet wurden. Zusätzlich wurde eine Aufnahme zehnmal ausgewertet. Die Berechnung der mittleren Winkelabweichung zwischen den Symmetrieebenen diente als Maß für die Reproduzierbarkeit der Methode.Ergebnisse:Die mittlere Winkelabweichung der berechneten Symmetrieebenen war mit 0,134° (zehn Aufnahmen nacheinander) und 0,177° (zehn Aufnahmen an verschiedenen Tagen) zwar signifikant höher als bei zehnmaliger Auswertung derselben Aufnahme (0,028°), ist jedoch als sehr gering zu bewerten. Bezüglich des Asymmetriegrades gab es keine statistisch signifikanten Unterschiede zwischen den drei Auswerteserien, die jeweiligen Standardabweichungen waren gering.Schlussfolgerungen:Mit Hilfe der vorgestellten Methode können reproduzierbar die Symmetrieebene sowie der Asymmetriegrad anhand von 3-D-Gesichtsdaten bestimmt werden. Durch die farbkodierte Visualisierung von asymmetrischen Gesichtsbereichen ermöglicht dieses Analyseverfahren eine wesentlich präzisere Diagnostik von Asymmetrien der Gesichtsweichteile als zweidimensionale En-face-Aufnahmen.

Face perception in patients with unilateral cleft lip and palate and patients with severe Class III malocclusion compared to controls

Although there is principal agreement that increased facial asymmetry is associated with decreased facial attractiveness, there are no studies analysing face perception in patients with a unilateral cleft lip and palate (CLP) (uCLP) compared to orthognathic Class III patients. To this end, three-dimensional (3D) data on the faces of 30 adults with a complete uCLP, 20 orthognathic patients with a severe skeletal Class III, and 20 adults with a skeletal Class I as a control group were generated. The 3D asymmetry of the facial soft-tissue was analysed. These data were compared with subjective ratings for attractiveness carried out by 100 laypersons. Compared to the controls, uCLP patients and orthognathic patients had a significantly higher facial asymmetry. No difference was found between uCLP patients and orthognathic patients. The attractiveness ratings showed that uCLP patients and orthognathic patients were rated less attractive compared to the controls. However, although there were no differences in the facial asymmetry between uCLP patients and orthognathic patients, the uCLP patients were rated significantly less attractive. This leads to the conclusion that not only the extent of asymmetry has an influence on attractiveness but also the location of asymmetry. For clinical use, these findings underline the importance of accurate as possible surgical reconstruction of the nasal morphology in uCLP patients.

Dentofacial Self-Perception and Social Perception of Adults with Unilateral Cleft Lip and Palate

ObjectiveThe aim of this study was to investigate the influence of facial asymmetry on how an adult population with unilateral cleft lip and palate (CLP) perceived themselves and were perceived by others.Patients and Methods3D facial data of 30 adult patients with cleft lip and palate (CLP) was scanned and standardized extra- and intraoral photographs were taken. The measured degree of 3D asymmetry was computed for the entire face, midface and lower face. Subjective estimates regarding facial symmetry, attractiveness as well as satisfaction and a desire or indication for further treatment were surveyed by means of a questionnaire filled out by patients and an assessment group (10 orthodontists, 10 oral and maxillofacial (OM) surgeons, 15 laypersons).ResultsThe study’s results show that the largest degree of asymmetry was found in the midface of CLP patients. The vast majority of the patients were dissatisfied with their facial appearance, and patients, experts and laypersons expressed great interest in and a need of correction. We observed tangible incongruence between how the patients perceived their own faces and how others perceived them.ConclusionsAsymmetry, especially in the midface, appears to detract from how facial appearance is self-perceived and perceived by others, which explains the primary desire for or need of nose correction. The self-perception of patients affected by CLP does not correlate with objective results or how others perceive them. Clinicians should be open to adult patients’ requests for correction, but the patient‘s self-perception should also be critically explored.ZusammenfassungZielZiel der Studie war es, den Einfluss der fazialen Asymmetrie auf die Selbst- und Fremdwahrnehmung bei Erwachsenen mit einseitiger Lippen-Kiefer-Gaumen-(LKG-)Spalte, nach Behandlungsabschluss zu untersuchen.Patienten und MethodikVon 30 erwachsenen Patienten mit LKG-Spalte wurden 3-D-Gesichtsdaten erhoben sowie standardisierte extra- und intraorale Fotografien angefertigt. Der gemessene 3-D-Asymmetriegrad wurde von dem gesamten Gesicht, dem Mittel- und dem Untergesicht berechnet. Subjektive Einschätzungen bezüglich der fazialen Symmetrie, Attraktivität sowie Zufriedenheit und weitere/r Behandlungswunsch/-indikation wurden mittels Fragebogen von den Patienten und einer Beurteilergruppe (10 Kieferorthopäden, 10 MKG-Chirurgen, 15 Laien) erhoben.ErgebnisseDie Ergebnisse der Studie zeigen, dass der größte Anteil der Asymmetrie im Mittelgesicht bei Patienten mit LKG-Spalte zu finden war. Der weitaus größte Teil der Patienten war unzufrieden mit dem fazialen Erscheinungsbild, und es bestand ein hoher Korrekturwunsch bzw. -bedarf vonseiten der Patienten, Experten und Laien. Eine deutliche Inkongruenz konnte zwischen der fazialen Selbstwahrnehmung des Spaltträgers und der Fremdwahrnehmung nachgewiesen werden.SchlussfolgerungenInsbesondere eine Asymmetrie im Mittelgesicht scheint die Fremd- und Selbstwahrnehmung des fazialen Aussehens negativ zu beeinflussen, wodurch sich der Korrekturwunsch bzw. -bedarf primär nach einer Nasenkorrektur erklären lässt. Patienten mit LKG-Spalten verfügen über eine Selbstwahrnehmung, die nicht mit den objektiven Ergebnissen bzw. der Fremdwahrnehmung korreliert. Der Kliniker sollte den Korrekturwünschen des erwachsenen Patienten offen gegenüberstehen, jedoch auch das Selbstbild des Patienten kritisch hinterfragen.

Persons with Cleft Lip and Palate are Looked at Differently

There is evidence that persons with cleft lip and palate (CLP) suffer psychosocial consequences as a result of their facial appearance. However, no data exist on how they are perceived by others. Our hypothesis was that CLP faces were looked at differently compared with faces lacking an anomaly. Eye movements of 30 healthy participants were recorded (via an eye-tracking camera) while they viewed photographs of faces with/without a CLP. Subsequently, the faces were rated for appearance, symmetry, and facial expression. When the CLP faces were viewed, there were significantly more initial fixations in the mouth and longer fixations in the mouth and nose regions, compared with reactions when control faces were viewed. Moreover, CLP faces were rated more negatively overall. When faces with CLP were viewed, attention was directed to the mouth and nose region. Together with the negative ratings, this may explain at least some of the social deprivations in persons with CLP, probably due to residual asymmetry.

Relation of melody complexity in infants' cries to language outcome in the second year of life: a longitudinal study.

This study is part of the German Language Development Studys prospective longitudinal research programme on infants from birth until the age of 3 years. Thirty‐four infants were retrospectively classified into two groups (normal/delayed) by their language skills at 2.5 years of age. Frequency spectrograms and melodies of about 11,000 cries from the first 16 weeks of life were analysed using a CSL 4400. A Melody Complexity Index was calculated at monthly intervals. Infants with less than 45% complex melodies in their cries during the second month were found to be almost five times more likely to develop a language delay as infants with a higher proportion. For infants above the cut‐off of .45, development of a language delay condition could be ruled out with a probability of 89%. Although the results need to be interpreted cautiously, the data indicate a possible relation between early melody development and later language outcome.

Visual Face Perception of Adults With Unilateral Cleft Lip and Palate in Comparison to Controls—An Eye-Tracking Study

Objective To assess how faces with a cleft lip and palate are perceived and to study how faces with and without a unilateral cleft lip and palate are viewed by individuals with a unilateral cleft lip and/or palate in comparison to nonaffected controls. Design Prospective clinical study. Setting Department of Orthodontics and Department of Psychology, University of Wuerzburg. Participants Thirty-three participants (20 men and 13 women; mean age, 25.4 ± 6.6 years) with a unilateral cleft lip and/or palate and a control group of 30 participants (15 men and 15 women; mean age, 26.8 ± 3.4 years) were enrolled in this study. Main Outcome Measures Eye movements were analyzed via an eye-tracking camera while all participants looked at pictures of faces with and without a unilateral cleft lip and palate. Results The nose and the mouth area of pictures of faces with a unilateral cleft lip and palate were looked at significantly longer by both groups. Additionally, the participants with a unilateral cleft lip and/or palate looked at faces with and without a unilateral cleft lip and palate differently, taking more time to view the nose and less time to view the eyes compared with the participants without a cleft lip and palate. Conclusion When perceiving a face with a unilateral cleft lip and palate, the observers gaze is distracted to the nose and mouth area. Moreover, participants with a unilateral cleft lip and/or palate themselves focused greater attention on those features that are anomalous on their own faces in comparison to participants without a cleft lip and palate. Specifically, this different scanpath is reflected in the cumulative duration of the eye movements as well as in the initial facial scan pattern.

Morphology of the sella turcica in Axenfeld-Rieger syndrome with PITX2 mutation

BACKGROUND Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and clinical morphology impresses with variable expressivity. Additionally to the typical craniofacial and dental aberrations anomalies in the morphology of sella turcica are discussed. METHOD In a multidisciplinary genetic and clinical study four patients of a family with ARS were screened by direct DNA sequencing. Radiographic analysis of the patients was performed for evaluating cranial and dental structures. Additionally, a specific analysis of the morphology of the sella turcica was made on the radiographs. RESULTS Screening for PITX2 and FOXC1 mutations revealed a P64L missense mutation in PITX2 in all four patients. The cephalometric analysis showed a midface hypoplasia associated with a skeletal Class III. All patients showed a sella turcica bridge combined with a prominent posterior clinoid process followed by a steep clivus and an elongated sella turcica. CONCLUSION The incidence of a sella turcica bridge in combination with a PITX2 mutation would suspect that sella turcica anomalies are typical symptoms of the syndrome. Sella turcica anomalies in association with craniofacial and dental aberrations, such as maxillary retrognathia, skeletal Class III relationship and hypoplasia of teeth, might be important indicators for ARS caused by PITX2 mutation.

Bridging of the sella turcica in skeletal Class III subjects

Several investigations have analysed the frequency of sella turcica anomalies in patients with severe craniofacial deviations. Until now, there have been no studies concerning the prevalence of sella turcica bridging in homogenous groups of patients. Therefore, the aims of this controlled study were to analyse the prevalence of sella turcica bridging and measure the size of the sella turcica in two well-defined groups of Caucasian individuals. In a multicentre retrospective study, 400 pre-treatment lateral cephalograms of adult patients (over 17 years of age) with a skeletal Class III (n = 250, 132 females and 118 males) or a skeletal Class I (n = 150, 94 females and 56 males) malocclusion were analysed. The morphology, length, depth, and diameter of the sella turcica were investigated. For statistical analysis, chi-square and t-tests were used. Skeletal Class III patients presented a significantly higher rate of sella turcica bridging, 16.8 per cent (P = 0.031), in comparison with skeletal Class I patients, whose rate was 9.4 per cent. No differences between females and males were detected for the length, depth, and diameter of the sella turcica. Bridging of the sella turcica could be seen radiographically in skeletal Class III subjects.