Maxillary shape after primary cleft closure and before alveolar bone graft in two different management protocols: A comparative morphometric study

AIM AND SCOPE: Result assessment in cleft surgery is a technical challenge and requires the development of dedicated morphometric tools. Two cohorts of patients managed according to two different protocols were assessed at similar ages and their palatal shape was compared using geometric morphometrics. MATERIAL AND METHODS: Ten patients (protocol No. 1) benefited from early lip closure (1-3 months) and secondary combined soft and hard palate closure (6-9 months); 11 patients (protocol No. 2) benefited from later combined lip and soft palate closure (6 months) followed by hard palate closure (18 months). Cone-Beam Computed Tomography (CBCT) images were acquired at 5 years of age and palatal shapes were compared between protocols No. 1 and No. 2 using geometric morphometrics. RESULTS: Protocols No. 1 and No. 2 had a significantly different timing in their surgical steps but were assessed at a similar age (5 years). The inter-canine distance was significantly narrower in protocol No. 1. Geometric morphometrics showed that the premaxillary region was located more inferiorly in protocol No. 1. CONCLUSION: Functional approaches to cleft surgery (protocol No. 2) allow obtaining larger inter-canine distances and more anatomical premaxillary positions at 5 years of age when compared to protocols involving early lip closure (protocol No. 1). This is the first study comparing the intermediate results of two cleft management protocols using 3D CBCT data and geometric morphometrics. Similar assessments at the end of puberty are required in order to compare the long-term benefits of functional protocols

AI-based diagnosis in mandibulofacial dysostosis with microcephaly using external ear shapes

IntroductionMandibulo-Facial Dysostosis with Microcephaly (MFDM) is a rare disease with a broad spectrum of symptoms, characterized by zygomatic and mandibular hypoplasia, microcephaly, and ear abnormalities. Here, we aimed at describing the external ear phenotype of MFDM patients, and train an Artificial Intelligence (AI)-based model to differentiate MFDM ears from non-syndromic control ears (binary classification), and from ears of the main differential diagnoses of this condition (multi-class classification): Treacher Collins (TC), Nager (NAFD) and CHARGE syndromes.MethodsThe training set contained 1,592 ear photographs, corresponding to 550 patients. We extracted 48 patients completely independent of the training set, with only one photograph per ear per patient. After a CNN-(Convolutional Neural Network) based ear detection, the images were automatically landmarked. Generalized Procrustes Analysis was then performed, along with a dimension reduction using PCA (Principal Component Analysis). The principal components were used as inputs in an eXtreme Gradient Boosting (XGBoost) model, optimized using a 5-fold cross-validation. Finally, the model was tested on an independent validation set.ResultsWe trained the model on 1,592 ear photographs, corresponding to 1,296 control ears, 105 MFDM, 33 NAFD, 70 TC and 88 CHARGE syndrome ears. The model detected MFDM with an accuracy of 0.969 [0.838–0.999] (p < 0.001) and an AUC (Area Under the Curve) of 0.975 within controls (binary classification). Balanced accuracies were 0.811 [0.648–0.920] (p = 0.002) in a first multiclass design (MFDM vs. controls and differential diagnoses) and 0.813 [0.544–0.960] (p = 0.003) in a second multiclass design (MFDM vs. differential diagnoses).ConclusionThis is the first AI-based syndrome detection model in dysmorphology based on the external ear, opening promising clinical applications both for local care and referral, and for expert centers

Many Labs 2: Investigating Variation in Replicability Across Samples and Settings

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely highpowered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Psicológicas (IIP

Sleep disordered breathing in Silver−Russell syndrome patients: a new outcome

International audienceOBJECTIVE: Imprinting disorders (ID), such as Prader-Willi syndrome (PWS), are associated with sleep-disordered breathing (SDB). No data are available for Silver-Russell syndrome (SRS), another ID that shares clinical features with PWS, although many patients describe excessive daytime sleepiness, disturbed sleep, and snoring. The aim of this study was to characterize sleep in children with SRS and to evaluate the impact of recombinant growth hormone (rGH) therapy.METHODS: We performed a retrospective analysis of sleep recordings in 40 patients with molecularly proven SRS (methylation anomaly in 11p15 [n = 32] or maternal uniparental disomy of chromosome 7 [n = 16]). Sleep recordings were either by means of polygraphy or polysomnography (PSG) (n = 16). A total of 34 patients received rGH therapy.RESULTS: We collected 61 sleep recordings. The mean apnea-hypopnea index (AHI) was 3.4 events/h (0-12.4), with a mean central AHI of 0.5 events/h (0-2.4). SDB was identified in 73.8% (n = 45) of the recordings and was severe in 4.9%. SDB was present in 86.4% of patients before rGH therapy and was severe in 13.6%. AHI worsened for 5 of 12 patients with sleep recordings before and after rGH therapy initiation, reaching mild impairment. The mean rGH dose was 32.3 μg/kg/(12.9-51.4), with a mean insulin-like growth factor 1 plasma level of 1.7 SDS (-1.9 to 6.6).CONCLUSION: Most patients with SRS present with SDB with an obstructive profile, possibly explained by narrowing of the airways and lymphoid organ hypertrophy. We recommend systematic ear-nose-throat evaluation of SRS patients and PSG if there are clinical anomalies, preferably before initiating rGH therapy, to monitor and adapt the management of patients with SDB

Diagnostic criteria in Pai syndrome: results of a case series and a literature review

IF 2.164 (2017)International audiencePai syndrome was originally described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present with the full triad, and most exhibit a wide spectrum of phenotypic variability. The aim of this study was to phenotypically delineate Pai syndrome and to propose new criteria to facilitate a clinical diagnosis in the future. The study cohort consisted of seven case patients and an additional 60 cases diagnosed with Pai syndrome identified in a literature review. Only 23 of 67 patients presented the full triad as historically described by Pai et al. (1987). A congenital facial midline skin mass was always encountered, particularly affecting the nasal structures (60/67). A midline facial cleft was reported in 45 of 67 patients and a pericallosal lipoma in 42 of 67 patients. The proposed definition of Pai syndrome is the association of (1) a congenital nasal and/or mediofrontal skin mass and/or a mid-anterior alveolar process polyp as a mandatory criterion, and at least one of the following criteria: (2) midline cleft lip and/or midline alveolar cleft, and/or (3) a pericallosal lipoma or interhemispheric lipoma in the case of corpus callosum dysgenesis

Craniofacial phenotype in the branchio-oculo-facial syndrome: four case reports

Branchio-oculo-facial syndrome represents a craniofacial disorder in which affected patients may develop a wide range of distinctive features that include cleft lip and/or palate, cervical aplastic skin defect, malformed pinna, and ocular anomalies. This study reports four new cases confirmed by the identification of mutations in the TFAP2A gene and describes in detail the findings in the craniofacial region. The four cases included two familial and two sporadic, and three have been followed since the birth. Two out of the four cases showed atypical features. One patient presented brainstem immaturity with dysregulation of sympathetic and parasympathetic systems, which have so far not been described in the literature and were associated with anxiety, panic attacks, and tiredness. Another patient had as an additional feature a hypoplastic thumb with distal implantation

Management of rare diseases of the Head, Neck and Teeth: results of a French population-based prospective 8-year study

International audienceAbstractBackgroundIn the last ten years, national rare disease networks have been established in France, including national centres of expertise and regional ones, with storage of patient data in a bioinformatics tool. The aim was to contribute to the development and evaluation of health strategies to improve the management of patients with rare diseases. The objective of this study has been to provide the first national-level data concerning rare diseases of the head, neck and teeth and to assess the balance between demand and supply of care in France.MethodsCentres of expertise for rare diseases record a minimum data set on their clinical cases, using a list of rare Head, Neck and Teeth diseases established in 2006. The present analysis focuses on 2008 to 2015 data based on the Orphanet nomenclature. Each rare disease RD “case” was defined by status “affected” and by the degree of diagnostic certainty, encoded as: confirmed, probable or non-classifiable. Analysed parameters, presented with their 95% confidence intervals using a Poisson model, were the following: time and age at diagnosis, proportions of crude and standardized RD prevalence by age, gender and geographical site. The criteria studied were the proportions of patients in Paris Region and the “included cases geography”, in which these proportions were projected onto the other French Regions, adjusting for local populations.ResultsIn Paris Region, estimated prevalence of these diseases was 5.58 per 10,000 inhabitants (95% CI 4.3-7.1). At December 31st 2015, 11,342 patients were referenced in total in France, of whom 7294 were in Paris Region. More than 580 individual clinical entities (ORPHA code) were identified with their respective frequencies. Most abnormalities were diagnosed antenatally. Nearly 80% of patients recorded come to Paris hospitals to obtain either diagnosis, care or follow up. We observed that the rarer the disease, the more patients were referred to Paris hospitals.ConclusionsA health network covering a range of aspects of the rare diseases problematic from diagnostics to research has been developed in France. Despite this, there is still a noticeable imbalance between health care supply and demand in this area

Calendrier et protocole interventionnel des fentes labiopalatines au sein du Service de chirurgie maxillo-faciale et plastique de l’Hôpital d’Enfants Trousseau (AP-HP, Paris)

La face est la partie visible, celle que les parents imaginent parfaite, elle marque l’identité du sujet tout au long de sa vie. La qualité du traitement primaire des fentes labiopalatines est essentielle et répond à un double objectif : restaurer une morphologie normale et une fonction normale. Les pronostics fonctionnel, morphologique et esthétique dépendent du caractère isolé ou associé de la fente à d’autres malformations, du caractère syndromique ou non. De la qualité de la réparation primaire dépendra également l’importance des séquelles. Celles-ci peuvent être la conséquence autant de la chirurgie et des autres thérapeutiques que de la malformation princeps. Avant 2000, le protocole adopté au sein du Service de chirurgie maxillo-faciale et plastique de l’Hôpital Armand-Trousseau (AP-HP, Faculté de médecine Pierre et Marie Curie) était celui décrit par Malek : véloplastie première à 3 mois puis chéiloplastie (avec triangle supérieur et inférieur) et fermeture du palais osseux à 6 mois. Nous avons opté pour une approche plus fonctionnelle telle que décrite par Talmant intégrant une chirurgie nasale systématique, une plastie labiale selon Millard et l’absence de zone osseuse dénudée résiduelle après fermeture de la fente osseuse. La gingivopériostoplastie avec greffe osseuse est réalisée entre 4 et 6 ans après traitement orthodontique et constitue la dernière étape du temps primaire. L’approche thérapeutique au sein du service a progressivement évolué depuis 20 ans, le but principal étant de s’approcher d’une réhabilitation ad integrum et de minimiser les séquelles en insistant sur la restauration des fonctions phonatoires, labiales et respiratoires et en évitant tout geste délétère pour la croissance faciale. L’approche multidisciplinaire intégrant l’évaluation des protocoles chirurgicaux est indispensable et justifie le traitement des patients porteurs de fentes labiopalatines au sein de centres labelisés

Interventional calendar and protocol for cleft lift and palate repair at the maxillofacial and plastic surgery department of the Armand Trousseau Children’s Hospital (AP-HP, Paris)

Parents want their children’s’ faces, the most visible part of their bodies, one that marks their identity throughout life, to be perfect. To satisfy this understandably urgent desire, a high quality of primary treatment for cleft lip and palate is essential and must satisfy a double objective: restore normal morphology and normal function. The functional, morphological, and esthetic prognoses depend on the character of the defect, whether it stands alone or is associated in a syndrome with other malformations. Important sequellae flow from the quality of the initial repair, as a consequence of the surgery and other therapies as well as from the deformity itself. Before the year 2000, the Maxillo-facial and Plastic Surgery Service at the Armand Trousseau Hospital of the Pierre and Marie Curie Faculty of Medicine adhered to the protocol that Malek had described, making an initial repair of the soft palate at 3 months and then a cheiloplasty, with upper and lower triangles, and closure of the hard palate at 6 months. Since then we have adopted the more functional approach that Talmant described, integrating systematic nasal surgery and the type of lip surgery that Millard suggested without leaving any residual exposed bone after closure of the osseous cleft. We then perform gingivo-periosteal surgery with bone grafts on patients when they were between 4 and 6 years of age, after orthodontic therapy had been completed. This constitutes the last stage of primary treatment. The therapeutic approach we have been using on our service, which has evolved of over the last 20 years, has come to define its principal objective as integration of extensive rehabilitation into the very first stages of our multi-disciplinary therapy so as to minimize the establishment of faulty functioning of phonation, lip competence, and ventilation while avoiding any intervention that would have a harmful impact on facial growth. This multi-disciplinary approach, which integrates surgical evaluation and protocol, is indispensable and fully justifies treatment of patients with cleft lip and palate at accredited centers

Initial treatment of alveolar gaps in cases of labio-maxillary-palatal clefts

Treatment teams use different approaches for correcting the alveolar cleft sector of labio-palatal clefts. Age of patient, whether or not bone grafts are used, and the type of bone grafted are some of the differences. Our team performs a gingivoperioplasty with a graft of iliac cancellous bone on patients 4 to 6 years old. This procedure is carried out within the framework of orthodontic treatment designed to restore transverse dimension pre-operatively with a quad helix and to retain the expansion with 6 months of retention. The gingivoperioplasty is accomplished in a zone free of any scar tissue that might have resulted from a primary cheiloplasty followed by closure of the palatal cleft. In our view all teams must eventually utilize cone beam X-rays for their radiographic evaluations because they are the only tool that provides results of objective analysis that are of high quality and have demanded a very low level of radiation