Commissuroplasty for macrostomia: surgical technique and long-term aesthetic and functional results assessment.

BACKGROUND: Macrostomia or lateral cleft lip is a rare congenital deformity. In this article we describe a surgical technique of macrostomia repair developed. The objective of this article is to assess the results of our surgical technique and to validate a method for macrostomia surgical result evaluation. METHODS: We included retrospectively patients with unilateral and bilateral macrostomia, operated from 1995 to 2014 in our department. First part of the study was a satisfaction questionnaire completed by patients. The second part was subjective evaluation of frontal photography (closed mouth, wide open and smiling) by surgeons and lay people with a questionnaire. Both group completed a second questionnaire within one to six months. RESULTS: Eighteen patients answered the questionnaire. The satisfaction for all patients were considered as very good for 38.9% (n = 7) of patients and good for 44.4% (n = 8). 21 patients were photographed, 5 isolated macrostomia, 13 macrostomia with minor facial asymmetry and 3 with a major asymmetry. Surgeons evaluated the result as very good for isolated macrostomia and good for syndromic macrostomia. Layperson evaluated the result as good in isolated macrostomia and macrostomia with minor facial asymmetry and average with major facial asymmetry. P < 0.0001. The evolution of the results between medical and non-medical assessors in our two questionnaires, were non-significant. CONCLUSION: In this study, we propose a new methodology to assess commissuroplasty surgical results, with a 3 type of evaluator: patients, surgeons and laypeople. We present a simple surgical technique, that allows good results in syndromic and isolated macrostomia.

Orofacial motor dysfunction in Moebius syndrome.

AIM: To review orofacial disabilities and their consequences in children with Moebius syndrome (MBS). METHOD: We retrospectively analysed the records of 32 patients (21 males, 11 females) with non-progressive bilateral facial and abducens palsies who had been examined before 6 months of age. RESULTS: All facial muscles were severely involved in 17 patients; in the 15 others, partial movements were found in the lower face. Most patients (n=24) were unable to smile. Patients frequently presented with congenital trismus (n=20) and drooling (n=18). Additional palsies involved cranial nerves IX and X (n=18) and XII (n=25). Sucking was absent or weak in 30 patients; swallowing was impaired in 25. During the first month of life, feeding disorders were graded as severe/moderate in 25. Respiratory complications occurred in 17. Severe feeding disorders were associated with congenital trismus (p=0.01) and with cranial nerve IX and X palsy (p=0.01). Growth failure between 1 and 6 months of age, followed by catch-up growth between 6 and 12 months, was observed in 20 patients. Between 2 and 5 years of age, 25 out of 32 patients attained normal oral diet and 28 out of 29 showed normal growth. INTERPRETATION: Children with MBS frequently require adjusted therapeutic options to prevent failure to thrive. Congenital trismus, cranial nerve IX and X palsy, and laryngeal-tracheal dysfunctions are predictors of severe feeding disorders. WHAT THIS PAPER ADDS: Moebius syndrome frequently induces reduced oral intake and early failure to thrive. Normal oral diet and growth parameters are attained at 2 to 5 years of age. Congenital trismus, pharyngeal palsy, and laryngeal disorders predict dysphagia.

Conservative management is effective in unicystic ameloblastoma occurring from the neonatal period: A case report and a literature review.

Unicystic ameloblastoma (UA), a benign odontogenic tumor of the jaw, represents less than a third of all ameloblastomas and seems less aggressive than other types of ameloblastoma. We present here the first case of UA that developed prenatally and was successfully managed in the early neonatal period with marsupialization and curettage performed carefully to avoid injury to the tooth germ. BRAF and SMO mutations were not detected. After 2 years of follow-up, complete reossification and normal eruption of deciduous teeth were noted, and there was no recurrence of UA. We recommend conservative treatment of UA in the pediatric population to avoid loss of and/or injury to the tooth germ, provided close follow-up is carried out all through the individual's growth for early detection of potential recurrences, growth impairments, or tooth eruption disorders. The intratumoral somatic mutational status of BRAF, SMO, RAS family, and FGFR2 may help determine personalized targeted treatment, particularly in case of recurrence.

Oral health related quality of life of children and adolescents affected by rare orofacial diseases: a questionnaire-based cohort study.

BACKGROUND: Rare diseases affecting the teeth, the oral cavity and the face are numerous, each of them present specific characteristics, and is a life-long condition. The aim of the study was to assess the association between Oral health-related quality of life (OHRQoL), and demographic characteristics, clinical and dental factors, and psycho-social characteristics to investigate that oral symptoms are not the main factors underlying a decrease in OHRQoL. MATERIAL AND METHODS: We conducted a national cohort study in French centres for rare diseases (RD) specialized in orofacial diseases. The inclusion criteria were: to have received care in RD centres over the last 5 years (2012-2017) and to have been between 6 and 17 years of age on September 1, 2017. Patients were invited to answer a questionnaire composed of socio-demographic, clinical and dental questions, psychosocial questions and then fill in the Child-OIDP Index. At the end of the questionnaire, a free space was left for the patient to add a verbatim comment to provide qualitative data. Thematic analysis was used to analyze the verbatim answers. RESULTS: Complete data were available for 110 patients. The sample included 44.5% boys and 55.5% girls. Ages ranged from 6 to 17 years old and 68.2% were between 6 to 12 years old and 31.8% were between 13 and 17 years old. Factor associated with a lower OHRQoL were: being a girl (p = 0.03), renouncement to dental care for financial reasons (p = 0.01), having syndromic disease (p = 0.01), having a problem with tooth shape and color (p = 0.03), feeling isolated, alone and different from other children (p = 0.003 and p = 0.02). Qualitative analysis highlighted very little recourse to psychological care and patients reported great anxiety and fear about the future. CONCLUSION: OHRQoL of children suffering from these diseases is impaired, especially from the psychosocial point of view but also from that of the course of treatment and access to care. There is a need to improve the legibility of care pathways and the financial coverage of treatments.

Severity of Retrognathia and Glossoptosis Does Not Predict Respiratory and Feeding Disorders in Pierre Robin Sequence.

Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and glossoptosis with those of respiratory and feeding disorders, we retrospectively studied a series of 50 infants with retrognathia, glossoptosis, cleft palate, and airway obstruction. The patients were managed from birth to at least 6 years of age by a single pediatric team at the Armand Trousseau Hospital in Paris within a 12 years period (2000-2012). Retrognathia and glossoptosis were graded in the neonatal period according to a specific clinical examination. Ventilation assistance was required for 32/50 (64%) patients, and enteral feeding for 41/50 (82%). The grades of retrognathia and glossoptosis and the severity of respiratory disorders did not differ between patients with isolated PRS and syndromic PRS. Severe respiratory disorders were more common and long-lasting feeding (>12 months) was more frequently required in patients with syndromic PRS compared with isolated PRS (42 vs. 13%, p = 0.04 and 42 vs. 4%, p < 0.01 respectively). Using univariate analysis, neurological impairments and laryngomalacia were associated with severe respiratory disorders [Odds ratio (OR) 5.0, 95% CI 1.3-19.6; and OR 14.6, 95% CI 1.3-161.4; p < 0.05] as well as with long-lasting feeding (>12 months) disorders (OR 18.6, 95% CI 3.9-89.2 and OR 20.4, 95% CI 3,4-122.8; p < 10-2). Syndromic SPR status was also associated with severe respiratory disorders (OR 4.9, 95% CI 1-32.5; p < 0.05). Using multivariate analysis, only syndromic PRS status was predictive for severe respiratory disorders (adjusted OR 8, 95% CI 1.47-44.57; p < 0.05); and only neurological impairments remained a significant risk for long lasting feeding disorders (>12 months) (adjusted OR 21.72, 95% CI 3.4-138.63; p < 10-2). The grades of retrognathia and glossoptosis were not predictive factors for the severity of respiratory and feeding disorders. Conclusion: In children with PRS, the severity of clinical conditions may not correlate with anatomic variables but rather with laryngeal abnormalities, neurological impairement and syndromic PRS status.

Pathogenesis of cranial neuropathies in Moebius syndrome: Electrodiagnostic orofacial studies.

INTRODUCTION: We designed a retrospective study of 59 patients with congenital sporadic nonprogressive bilateral facial and abducens palsies. METHODS: Examinations included needle electromyography (EMG) of facial and oral muscles, facial nerve motor latency and conduction velocity (FNCV), and blink responses (BR). RESULTS: Neurogenic EMG changes were found in 1 or more muscles in 55 of 59 patients, with no abnormal spontaneous activity. EMG changes were homogeneously neurogenic in 17 patients, homogeneously myopathic in 1 patient, and heterogeneous in 41 of 59 patients. Motor latency was increased according to recordings from 52 of 137 facial muscles. An increase of motor latency was not associated with neurogenic EMG (Fischer's test: right, P = 1; left, P = 0.76). FNCV was slowed in 19 of 36 patients. BR was absent bilaterally in 35 of 58 patients; when present, R1 and R2 latencies were normal. DISCUSSION: Our results support the hypothesis of an early developmental defect localized in motor cranial nerves with spared V-VII internuclear pathways. Muscle Nerve, 2018.

Predictors of speech outcomes in children with Pierre Robin sequence.

BACKGOUND: Pierre Robin sequence (PRS) has worse speech outcomes than isolated cleft palate. We aimed to search for possible associations of phonological outcomes with PRS status (isolated vs syndromic), clinical severity, soft palate muscles deficiency, or surgical procedure. METHODS: We designed a retrospective study of 130 children (male/female ratio: 0.4) with isolated (96) or syndromic (34) PRS with cleft palate. Grading systems were used to classify retrognathia, glossoptosis, and respiratory and feeding disorders. Electromyography was used to investigate levator veli palatini muscles. Hard cleft palate was measured using maxillary casts. Intravelar veloplasty was performed using the Sommerlad's technique. Phonological outcomes were assessed using the Borel-Maisonny classification. RESULTS: Cleft palate was repaired in one stage (65.5%) or hard palate closure was postponed (34.5%). Velopharyngeal insufficiency was more frequent in syndromic PRS (53%) vs. isolated PRS (30.5%) (p = 0.01), but was not statistically associated with clinical grade, hard cleft palate width, soft palate electromyography, and surgical procedure. CONCLUSIONS: In children with PRS, anatomic variables, initial clinical severity, and soft palate muscle deficiency are not predictors of speech prognosis.

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

BACKGROUND: In 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. METHODS: Centres 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. RESULTS: In 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. CONCLUSIONS: A 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.

Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism.

Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism.

Ethical Issues in Pediatric Face Transplantation: Should We Perform Face Transplantation in Children?

BACKGROUND: In 2005, face transplantation ceased to be fiction and became a scientific reality. Today, 10 teams from six different countries have performed 32 face transplantations. Immunosuppressive treatments are similar to other solid organ transplants, and patients have experienced a significant functional improvement. The authors are logically considering expanding face transplantation to children; however, children are not simply small adults. METHODS: The authors searched for pediatric patients in need of restoration of fundamental functions of the face, such as orbicularis oris or oculi muscle closure by, first, selecting cases from a pediatric plastic surgery reference center and, second, analyzing the feasibility of face transplantation in those patients. The authors then identified the specific problems that they would encounter during a pediatric face transplant. The authors identified three potential candidates for pediatric face transplantation. RESULTS: Children's youth imposes additional ethical and psychological considerations, such as the balance of risk to benefit when it is quality of life, not life itself, that is at stake; the process of informed consent; the selection process; and the protection of privacy against media exposure. The question becomes not whether children should be included as candidates for face transplantation but whether any ethical barriers should preclude children as candidates for a full face transplant. CONCLUSION: After careful consideration of the physical, psychological, and ethical aspects of such a procedure, the authors found no such barrier that would either disqualify such vulnerable subjects as profoundly disfigured children or conflict with their best interests.

Outcomes of Neonatal Bulbar Weakness.

BACKGROUND AND OBJECTIVE: Neonatal bulbar weakness (BW) has various etiologies and a broad prognostic range. We aimed to report outcomes in a large series of children with neonatal BW and explore the association of orofacial electrodiagnostic data with outcome. METHODS: We retrospectively reviewed the files of children who presented with facial, lingual, laryngeal, or pharyngeal weakness at birth and who underwent electrodiagnostic studies combining conventional needle electromyography (EMG) of orofacial muscles, blink responses, and EMG during bottle-feeding. Outcome measures included the need for prolonged respiratory assistance and enteral feeding, as well as sensorimotor and cognitive impairments. RESULTS: Of 175 patients, 73% had developmental disorders, 25% suffered from acquired brain damage, and 2% had no apparent underlying disorders. Motor or mental impairment was observed in 71%; death occurred in 16%. Outcomes were not significantly different when comparing developmental disorders versus acquired brain damage or neurogenic versus normal detection EMG. Abnormal blink responses were associated with higher frequencies of respiratory assistance (P = .03), gastrostomy (P = .025), and death (P = .009); moderate or severe oropharyngeal incoordinations were associated with higher frequencies of respiratory assistance (P = .006), prolonged enteral feeding (P < .0001), and gastrostomy (P = .0002). CONCLUSIONS: Orofacial electrodiagnostic studies provide supplementary information to help the pediatrician anticipate the management and prognosis of young infants with BW.

Evaluation of 5-year-old children with complete cleft lip and palate: Multicenter study. Part 2: Functional results.

BACKGROUND AND PURPOSE: Cleft surgery is marked by all the controversies and the multiplication of protocols, as it has been shown by the Eurocleft study. The objective of this pilot study is to start a comparison and analyzing procedure between primary surgical protocols in French centers. METHODS: Four French centers with different primary surgical protocols for cleft lip and palate repair, have accepted to be involved in this retrospective study. In each center, 20 consecutive patients with complete cleft lip and palate (10 UCLP, 10 BCLP per center), non syndromic, have been evaluated at a mean age of 5 [range, 4-6]. In this second part, maxillary growth and palatine morphology were assessed on clinical examination and on dental casts (Goslon score). Speech was also evaluated clinically (Borel-maisonny classification) and by Aerophonoscope. RESULTS: Veau-Wardill-Killner palatoplasty involves a higher rate of transversal maxillary deficiency and retromaxillary. The fistula rate is statistically lower with tibial periosteum graft hard palate closure but this technique seems to give retromaxillary. Malek and Talmant two-stage-palatoplasty techniques reach Goslon scores of 1 or 2. Considering speech, Sommerlad intravelar veloplasty got higher outcomes. CONCLUSIONS: Primary results. Extension to other centers required. The two-stage palatoplasty, including a Sommerlad intravelar veloplasty seems to have the less negative impact on maxillary growth, and to give good speech outcomes. LEVEL OF EVIDENCE: Therapeutic study. Level III/retrospective multicenter comparative study.

Evaluation of 5-year-old children with complete cleft lip and palate: Multicenter study. Part 1: Lip and nose aesthetic results.

BACKGROUND AND PURPOSE: Cleft surgery is marked by all the controversies and the multiplication of protocols, as it has been shown by the Eurocleft study. The objective of this pilot study is to start a comparison and analyzing procedure between primary surgical protocols in French centers. METHODS: Four French centers with different primary surgical protocols for cleft lip and palate repair, have accepted to be involved in this retrospective study. In each center, 20 consecutive patients with complete cleft lip and palate (10 UCLP and 10 BCLP per center), non syndromic, have been evaluated at a mean age of 5 [4,6]. In this first part, the aesthetic results of nose and lip repair were assessed based on the scale established by Mortier et al. (1997). RESULTS: Considering nose outcome, primary cleft repair surgery including a nasal dissection gives a statistically significant benefit in terms of septum deviation. Considering lip result, muscular dehiscence rate is significantly higher in BCLP patients with a two-stage lip closure. The centers using Millard one-stage lip closure do not have uniform results. For UCLP patients, the quality of scar is not statistically different between Skoog and Millard techniques. CONCLUSIONS: Primary results based on a simple, reproducible evaluation protocol. Extension to other centers required. LEVEL OF EVIDENCE: Therapeutic study. Level III/retrospective multicenter comparative study.

Functional assessment of disease-associated regulatory variants in vivo using a versatile dual colour transgenesis strategy in zebrafish.

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function.

Osseous and dental outcomes of primary gingivoperiosteoplasty with iliac bone graft: A radiological evaluation.

Primary alveolar cleft repair has two main purposes: to restore normal morphology and normal function. Gingivoperiosteoplasty with bone grafting in mixed dentition has been a well-established procedure. We hypothesized that 1) performance of this surgery in deciduous dentition would provide favorable bone graft osseointegration, and 2) would improve the support of incisor teeth eruption, thereby avoiding maxillary growth disturbances. We conducted a retrospective study of clinical and tridimensional radiological data for 73 patients with alveolar clefts (with or without lip and palate clefts) who underwent gingivoperiosteoplasty with iliac bone graft in deciduous dentition. Pre- and post-operative Cone Beam Computed Tomography (CBCT) comparison allowed evaluation of the ratio between bone graft volume and initial cleft volume (BGV/ICV ratio), and measurement of central incisor teeth movements. This series of 73 patients included 44 males and 29 females, with a mean age of 5.5 years. Few complications were observed. Post-operative CBCT was performed at 7.4 months. The mean BGV/ICV ratio was 0.62. Axial rotation was significantly improved post-operatively (p = 0.004). Gingivoperiosteoplasty with iliac bone graft is safe when performed in deciduous dentition and results in a sufficient bone graft volume to support lateral incisor eruption and upper central incisor tooth position improvement.

Congenital multiple cranial neuropathies: Relevance of orofacial electromyography in infants.

INTRODUCTION: The aim of this study was to assess diagnoses and outcomes of infants with 2 or more cranial neuropathies identified using orofacial electromyography (EMG). METHODS: This retrospective study involved 90 patients. Diagnoses took into account clinical, radiological, and genetic data. EMG examined the orbicularis oculi, genioglossus, and levator veli palatini muscles, and blink responses. To evaluate outcome, neurological disability, respiratory complications, and feeding difficulties were recorded. RESULTS: The patients had malformation syndromes (59), encephalopathies (29), or no underlying disorders (2). Neurogenic EMG signs were detected in a mean of 4 muscles, reflecting a mean of 3 affected nerves. EMG identified a higher number of neuropathies than clinical examination alone (82 vs. 31, facial; 56 vs. 2, pharyngeal; 25 vs. 3, hypoglossal). Poor outcome and death were more frequent when EMG identified ≥4 affected nerves (P = 0.02). CONCLUSION: EMG highlights multiple cranial neuropathies that can be clinically silent in infants with malformation syndromes or encephalopathies.

Skeletal and soft tissue changes and stability in cleft lip and palate patients after distraction osteogenesis using a new intraoral maxillary device.

BACKGROUND: The authors have recently reported on the use of an internal maxillary distraction device. In this study, we report on the hard and soft tissue movements achieved with this intraoral distraction device, and the stability changes after distraction osteogenesis for maxillary hypoplasia in patients with cleft lip and palate. METHODS: Ten male patients with severe hypoplasia of the maxilla, with complete uni- or bilateral cleft lip and palate were included. The mean age of the patients at the time of operation was 11.91 years (±3.41). To evaluate the distraction process and stability, superimpositions on the preoperative lateral cephalograms were performed. The mean follow-up (FU) was 15.42 months (±3.94). RESULTS: Cephalometric measurements at all of the maxillary hard and soft tissue points improved significantly. Maxillary point A was advanced by 8.25 mm (±3.17; P < 0.001). After distraction soft tissue point A' had advanced 7.10 mm (±2.69; P < 0.001). The soft tissue to hard tissue ratio at point A was 0.86:1 after distraction. Maxillary horizontal relapse at point A was 14.1% at FU. Vertical relapse was not significant. CONCLUSION: This rigid intraoral distraction device can be successfully used in the correction of severe maxillary hypoplasia. The marked aesthetic improvement and low psychological encumbrance make this device viable for the treatment of cleft-related hypoplasia of the maxilla.

Primary cutaneous B-cell lymphoblastic lymphoma in children. Report of two cases.

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon high-grade neoplasm. Primary cutaneous B-LBL is uncommon and clinical diagnosis is difficult. We report two cases of primary cutaneous B-LBL that had initially been diagnosed as an infected dermoid cyst and lipoma, respectively, and referred for excision. The cases demonstrate the importance of biopsy and histopathologic examination of subcutaneous tumors to guide appropriate therapy.