Neanderthal-derived variants increase SOX9 enhancer activity in craniofacial progenitors that shape jaw development.

Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities.

'Pierre Robin' is one of the most readily recognised eponyms in medicine, yet it is a poorly understood nonspecific grouping of malformations that has no prognostic significance. Previously known as 'Pierre Robin syndrome', the way this diagnostic entity is viewed is now undergoing change. It is the purpose of this paper to review previous thinking about Robin and provide an update on recent clinical observations. A computerised literature search using MEDLINE, EMBASE, AJOL and OMIM was conducted for published articles up to March 2006. Mesh phrases used in the search were: Pierre Robin syndrome, Robin anomalad and Robin sequence (RS). This relatively uncommon association of micrognathia with cleft palate and upper airway obstruction which was initially thought to be a specific disease and entire treatment regimens established to deal with presumed problems is now understood to be a grouping of clinical findings that does not represent a distinct multiple anomaly syndrome. The condition is therefore now described as 'Pierre Robin sequence'. Evidence of distinct cytogenetic anomalies has also highlighted the aetiological heterogeneity associated with RS in recent times. Infants with Robin sequence can present with varied problems, some of them emergencies. Clinicians must be aware of the high prevalence of associated syndromes and the possible contribution of other syndromic features to the problems for proper patient care. Candidate loci and potential candidate genes are currently being proposed in the literature for RS.

Comparison of the differentiation potential of neural crest derived progenitor cells from apical papilla (dNC-PCs) and stem cells from exfoliated deciduous teeth (SHED) into mineralising cells

Tumor cell heterogeneity in neuroblastoma, a pediatric cancer arising from neural crest-derived progenitor cells, presents clinical challenges. Unlike adrenergic (ADRN) neuroblastoma cells, neuroblastoma cells with a mesenchymal (MES) identity are resistant to chemotherapy and retinoid therapy, which contributes to relapses and treatment failures. We explored whether up-regulation of the neurogenic, tumor suppressor microRNA miR-124 could promote the differentiation of retinoic acid-resistant MES neuroblastoma cells. Leveraging our screen for miRNA-modulatory small molecules, we identified and validated the tyrosine and phosphoinositide kinase inhibitor PP121 as a robust inducer of miR-124. Combining PP121 and BDNF-activating bufalin synergistically arrested proliferation and promoted the sustained differentiation of MES/heterogeneous SK-N-AS cells over several weeks. This protocol also resulted in the differentiation of multiple MES neuroblastoma and glioblastoma cell lines. RNA-seq analysis of differentiated MES/heterogeneous SK-N-AS cells revealed the replacement of the ADRN core regulatory circuitry with circuitries associated with chromaffin cells and Schwann cell precursors. Furthermore, differentiation was associated with inhibition of the CDK4/CDK6 pathway and activation of a transcriptional program that correlated with improved outcomes for patients with neuroblastoma. Our findings suggest an approach with translational potential to induce the differentiation of therapy-resistant cancers of the nervous system. Moreover, these long-lived, differentiated cells could be used to study mechanisms underlying cancer biology and therapies.

Membrane-Bound Neuregulin1 Type III Actively Promotes Schwann Cell Differentiation of Multipotent Progenitor Cells

Pierre Robin sequence results from a cascade of events that occur during embryologic development and frequently presents with cleft palate. Some studies have shown speech outcomes to be worse in patients with Pierre Robin sequence after cleft palate repair. A cohort of Pierre Robin sequence patients who all required an airway intervention and nasogastric feeding in the neonatal period were identified and speech outcomes assessed at 5 years of age. A cleft- and sex-matched non-Pierre Robin sequence, cleft palate-only comparison group was also identified from the same institution and study period. A total of 24 patients with Pierre Robin sequence that required airway and nutritional support in the neonatal period were matched for age, sex, and cleft type to a group of 24 non-Pierre Robin sequence cleft patients. There was no significant difference in the incidence of oronasal fistula between the groups. Secondary surgery for velopharyngeal incompetence was significantly more (p = 0.017) in the Pierre Robin sequence group, who also had significantly greater nasality (p = 0.031) and cleft speech characteristic (p = 0.023) scores. The authors hypothesize that other factors may exist in Pierre Robin sequence that may lead to poor speech outcomes. The authors would suggest counseling parents of children with Pierre Robin sequence that have required a neonatal airway intervention, that speech development may be poorer than in other children with cleft palate, and that these children will have a significantly higher incidence of secondary speech surgery. Risk, II.

Relevance. Despite extensive investigation of Pierre Robin sequence (PRS), significant challenges remain in the treatment and rehabilitation of infants with congenital cleft lip and palate, including alveolar and palatal clefts affecting craniofacial development across the transverse, vertical, and sagittal planes. The coexistence of cleft palate and Pierre Robin sequence substantially complicates orthodontic management at different stages of neonatal care. In PRS, cleft palate associated with glossoptosis and micrognathia frequently results in acute airway obstruction and feeding difficulties, necessitating urgent specialized orthodontic care within the first 24 hours after birth. Materials and methods. To achieve the study objectives, a novel orthodontic appliance was developed (patent application No. 2025101519, January 25, 2025). The appliance was used as an emergency intervention in five newborns with mild to moderate Pierre Robin sequence during the first days of life. Clinical use was carried out at the Perinatal Center (Neonatal Pathology Unit) and the Dental Department of the Clinical Diagnostic Center of Republican Hospital No. 1 – National Center of Medicine named after M. E. Nikolaev (Yakutsk, Russian Federation). Results. Newborns adapted to the appliance within the first three days, with restoration of airway patency and sucking function, allowing independent oral feeding and subsequent removal of the nasogastric tube when clinically indicated. The appliance was worn continuously and cleaned once daily using infant soap. Replacement of the appliance was planned after 1.5–2 months, based on the infant’s growth and weight gain and following endoscopic reassessment. Conclusion. Use of an anti-glossoptosis orthodontic appliance with a contoured palatal surface and a targeted intra-cleft extension enables effective early management of acute respiratory compromise and feeding difficulties in newborns with Pierre Robin sequence during the first days of life.

The aim of this study was to evaluate pre-operative nutritional status, associated syndromes and abnormalities, and post-operative outcomes of patients with Pierre Robin Sequence (PRS) versus those with non-syndromic isolated cleft palate (CIP). Between January 1995 and December 2013, patients with a cleft palate Veau I-II according to the Veau classification with and without PRS who underwent primary repair were retrospectively analyzed. The nutrition status, age at the time of palatoplasty, additional anomalies, gestational complications, and post-operative speech abnormalities and outcomes were evaluated. A total of 59 patients with PRS (PRS group) and 132 patients without PRS (non-PRS group) were included in the study. Of all patients, 92 were males and 99 were females with a mean age of 14 ± 4.18 (range, 6 to 26) years. The rate of gestational complications, enteral nutrition, complete cleft, additional anomalies, and velopharyngeal insufficiency was significantly higher in the PRS group (P < 0.05). However, the incidence of fistulas and age at the time of palatoplasty did not significantly differ between the groups. Based on our study results, enteral nutrition, respiratory problems, pregnancy complications, velopharyngeal insufficiency, and additional anomalies, but not post-operative palatal fistulas, are more frequently seen in patients with PRS. Although pre-operative care and treatment and rehabilitation in patients with PRS are more complicated than those with the CIP, our experience demonstrates that meticulous repair and follow-up can minimize complications, such as fistulas.

PurposeThis study aimed to evaluate the effectiveness of the four-section approach using two-dimensional sonography in diagnosing Pierre Robin sequence (PRS) during second-trimester screening.MethodsA prospective study was conducted on low-risk pregnant women undergoing routine mid-trimester screening. Cases with suspected micrognathia prenatally were included and examined using the four-section approach. Initially, we measured the inferior facial angle (IFA) for fetuses suspected of having micrognathia. Subsequently, in the oblique coronal section via the oral fissure, we examined the continuity of the hard and soft palate line. Finally, dynamic scanning of both the sagittal and coronal sections of the mandible was performed to confirm whether the echogenic tongue was displaced posteriorly. All fetuses diagnosed with PRS were followed up through autopsy and postnatal evaluation.ResultsForty-three fetuses were initially subjectively suspected of having micrognathia by sonographers. After objective IFA measurement, 25 cases had an IFA < 50°, while 18 had an IFA > 50°. Among the 25 cases with IFA < 50°, we identified 13 cases of PRS with micrognathia, cleft palate (CP), and glossoptosis. However, one case failed to be diagnosed prenatally because it had micrognathia and CP but no glossoptosis. Eleven cases had neither CP nor glossoptosis yet exhibited other malformations. Among the 18 fetuses with IFA > 50°, 15 cases were normal, while three cases had other deformities. In this study cohort, no false-positive results were found. The four-section approach for diagnosing PRS showed a sensitivity of 92.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 91.7%.ConclusionThe four-section method proved highly effective in assessing PRS during second-trimester sonographic scans. The combined evaluation of micrognathia and glossoptosis can remarkably enhance the accuracy of prenatal PRS diagnosis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10396-025-01556-x.

To What Extent is Each Area of Oral-Maxillofacial Surgery Practiced in the United States Today?

Mandibular Traction—An Alternative Treatment in Infants With Pierre Robin Sequence

1. Matthew R. G. Taylor, MD* 1. 2. *Division of Genetic Services, University of Colorado Health Sciences Center, Denver, CO. The Pierre Robin sequence (PRS) describes a clinical triad of cleft palate, micrognathia, and glossoptosis. The condition is considerably more complicated than isolated cleft palate. Substantial respiratory and feeding problems may arise in affected individuals. A timely diagnosis made by an experienced pediatrician is important in attenuating these feared consequences. Several causes of PRS have been elucidated, some of which are heritable and have implications for other siblings and future children. A male infant was born to a G2P1 → 2 healthy mother at 36.5 weeks of gestation. The pregnancy was complicated by maternal hypertension. Normal fetal movements and normal amniotic fluid were reported. The birthweight was normal, and initial Apgar scores were 7 and 9 at 1 and 5 minutes, respectively. The infant was noted to have a “small” jaw and within 1 hour of birth was experiencing significant respiratory difficulties and cyanosis. High-flow oxygen and placement in a prone position improved his condition only transiently, and he was transferred to a tertiary care hospital. A cleft palate was noted, and shortly after arrival, endotracheal intubation was performed due to his deteriorating respiratory status. Severe PRS was suspected, and a tracheostomy was performed on day 10 of life. The genetic evaluation noted an unremarkable family history. No relatives suffered from PRS, cleft palate, or features of an obvious related genetic condition. Physical examination revealed a weight of 3,050 g (50th percentile), head circumference of 32.5 cm (40th to 50th percentile), and length of 52 cm (90th percentile). His facial features were striking and included severe micrognathia, a palatal cleft, and obvious midface hypoplasia. His eyes and ears appeared normal. No heart murmur was noted, and findings on abdominal, genital, and extremity examinations were normal. The geneticist suspected Stickler syndrome based on the PRS and the facial features. The diagnosis …

Cleft lip with or without cleft palate (CL/P) and cleft palate (CP) result from incomplete merging and fusion of embryonic processes during formation of the face. Microforms of clefting are also known to occur, the best example being submucous CP. In this condition there is incomplete fusion of the muscular layers of the velum (soft palate) with fusion of the overlying mucosa. In children and adults with submucous CP, the clinical features are highly variable, ranging from an isolated, inconspicuous clinical finding of bifid uvula to severe speech (hypernasality) and feeding difficulties, often with attendant chronic otitis media. Cleft palate and CL/P have multiple etiologies as well. They are often associated with underlying syndromes. Additionally, orofacial clefts are classified by anatomical involvement. This includes unilateral cleft lip, bilateral cleft lip, cleft lip with cleft palate (generally indicating involvement of the primary and secondary palates) cleft palate, and cleft palate secondary to Pierre Robin sequence4 (Figs. 25–1, 25–2, and 25–3). Hundreds of disorders have been associated with orofacial clefts, including both genetic and teratogenic conditions. Among the most common causes of cleft palate is the Pierre Robin sequence. This specifically refers to disruption of normal elevation of the fusion of the palatal shelves secondary to micrognathia and a posterally placed tongue (Fig. 25–2). Like all orofacial clefts, Pierre Robin sequence can be caused by multiple underlying disorders.

Objective To evaluate the efficacy of airway topical anesthesia with combination of superior laryngeal nerve block (SLNB) and thyrocricoid membrane puncture for tracheal intubation in the pediatric patients with Pierre Robin Sequence. Methods Thirty-two American Society of Anesthesiologist physical status Ⅰ or Ⅱ pediatric patients with Pierre Robin Sequence, aged 5-12 months, weighing 5-13 kg, scheduled for elective cleft palate repair under general anesthesia, were divided into 2 groups (n=16 each) using a random number table method: control group (group C) and airway topical anesthesia with SLNB-thyrocricoid membrane puncture group (group ST). After anesthesia was induced by inhaling sevoflurane by mask on admission to the operating room, 2% lidocaine 0.5 ml was injected around the bilateral superior laryngeal nerve under ultrasound guidance, and then 2% lidocaine 1 ml was injected via the thyrocricoid membrane in group ST, and the root of tongue, pharynx and larynx were sprayed with 2% lidocaine by using a laryngotracheal mucosal atomization device in group C. The pediatric patients were tracheally intubated guided by a video laryngoscope 3 min later.The development of cardiovascular responses, vocal cord activity and body movement was recorded during intubation.The intubation time, success rate of intubation at first attempt and patient′s tolerance to tube were recorded.The occurrence of postoperative hoarseness was also recorded. Results Compared with group C, the incidence of cardiovascular responses, vocal cord activity and body movement was significantly decreased, the intubation time was shortened, the success rate of intubation at first attempt was increased, and the patient′s tolerance to tube score was decreased in group ST (P<0.05). Conclusion Airway topical anesthesia with combination of SLNB and thyrocricoid membrane puncture can provide better intubation conditions when used for the pediatric patients with Pierre Robin Sequence. Key words: Nerve block; Anesthesia, local; Intubation, intratracheal; Pierre Robin Syndrome

Pierre Robin syndrome is characterized by micrognathia, glossoptosis, and cleft palate. Infants with Pierre Robin syndrome causes feeding difficulty, upper airway obstruction, and other symptoms. This study aims to examine the effects of applying dysphagia treatment to infants with Pierre Robin syndrome. The study participant was an infant who was born four weeks premature and referred for dysphagia treatment approximately 100 days after birth. At the initial assessment, the infant showed oral sensory sensitivity, a high level of facial and masticatory muscle tension, and a low stability of the chin and cheeks with almost no normal “sucking-swallowing-breathing” pattern. We set the baseline period and intervention period using the AB design. During the baseline period, non-nutritive sucking training using a rubber nipple was conducted without implementing an oral stimulation intervention. During the intervention period, non-nutritive sucking training and an oral stimulation intervention were performed. After the intervention period, the infant’s daily oral intake and oral intake per time significantly increased compared to that during the baseline period. We observed that the oral intake time of the infant decreased during the intervention period compared to that in the baseline period, which indicated an improvement in control over the chin, tongue, and lip movements, a change in muscular tension, and stabilization of the “sucking-swallowing-breathing” pattern. We provided dysphagia treatment before breastfeeding, it was positive effects such as normal development of the infant, transition from tube feeding to bottle feeding, and enhancement of overall oral motor function.