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The results of a survey of twenty-four neonatal units in the United Kingdom and Ireland are presented. A structured ten-item questionnaire was used, and demonstrated the variation in how infants with RS are diagnosed and managed. Notably, the survey revealed that a minority of infants were diagnosed antenatally. There were significant discrepancies in diagnostic criteria used and 79% of the units referred the patients to tertiary services. A preference for minimally invasive approaches to managing upper airway obstruction, such as a trial of prone positioning before progressing to a nasopharyngeal airway, was reported by 96% of the centers. A narrative review was undertaken which discusses the current practices for diagnosis and early management of Robin sequence (RS). The challenges of antenatal diagnosis, strategies to enhance outcomes through early detection and controversies surrounding the management of neonatal upper airway obstruction associated with RS are included. The results of the survey and our comprehensive review of the literature emphasize that there remains uncertainty regarding the best approach to treating Robin sequence. [ABSTRACT FROM AUTHOR]

Background: Pierre Robin Sequence (PRS) presents in isolation [iPRS] or in conjunction with a genetic syndrome [sPRS] that can subsequently lead to respiratory dysfunction and eventual failure to thrive. Mandibular distraction osteogenesis (MDO) has gained popularity as a way to surgically address the airway obstruction in PRS. sPRS patients routinely have a more challenging clinical course, and there is a paucity of data comparing the effectiveness of MDO as a treatment for sPRS versus iPRS. That said, this study analyzed MDO in both sPRS and iPRS patients within a relatively large single institution cohort. Methods: A retrospective review was conducted on all PRS patients who underwent MDO by a single surgeon between 2015 and 2022. The patients were stratified into iPRS or sPRS based on genetic evaluation (N = 50). Primary measures were demographic and situational data; outcome measures included tracheostomy and gastrostomy tube (g-tube) avoidance, Apnea-Hypoxia Index (AHI), and laryngeal view predistraction and at time of distractor removal. Results: Prior to distraction, iPRS (N = 32) and sPRS (N = 18) patients showed no significant differences in age (105.1 ± 199.7 days; range 2-1051 days), AHI (17.3 ± 17.1; range 3.6-90), or laryngeal view (65% grade III or IV) (P >.05). Overall, post-MDO, there was a statistically significant decrease in mean AHI 17.3 to 4.5 (P <.001). sPRS patients in particular had a significant decrease in average AHI following MDO from 15.2 to 4.5 (P =.028). Post-MDO both groups had similar improvement of laryngeal view, and avoidance of g-tube (P <.05). Conclusions: MDO was found to be an effective technique to improve airway obstruction in both sPRS and iPRS. Despite the fact that sPRS patients typically have a more challenging clinical course, an equivalent clinical improvement in airway outcomes was seen between sPRS and iPRS patients post-MDO. [ABSTRACT FROM AUTHOR]

Robin Sequence (RS) is a collection of distinct morphologic features involving the face and upper airway that results from the abnormal development of the neonatal mandible. Typically described as the triad of micrognathia, glossoptosis, and upper airway obstruction, it is frequently associated with a cleft palate and can be found in isolation or as part of a syndromic presentation. Owing to the intimate relationship between the mandible and its soft tissue attachments, micrognathia manifests clinically with respiratory and feeding difficulties. There is significant heterogeneity in both the degree of anatomic aberration and the associated physiological compromise, which dictates the medical and surgical treatment plan. In severe cases requiring surgical intervention, mandibular distraction osteogenesis (MDO) has been shown to be successful in relieving airway obstruction by correcting the morphologic deficiency of the mandible. However, controversy persists regarding the best treatment method as the exact relationship between the anatomic changes affected by MDO and the physiologic improvement remains poorly understood. This controversy is fueled by differing opinions about the natural growth potential of the abnormal mandible in patients with RS and the lack of long-term data on the maxillomandibular relationship at skeletal maturity of patients who underwent MDO in infancy. The objective of this systematic review is to provide a comprehensive summary of the morphologic changes to the mandible, upper airway, and hyoid bone affected by MDO and the impact of these changes on physiologic improvement and long-term growth. [ABSTRACT FROM AUTHOR]

Background: Cerebro-costo-mandibular syndrome (CCMS) is a rare congenital syndrome consisting of the main features of micrognathia and posterior rib gaps. Due to multiple abnormalities, patients almost have difficulty breathing with upper airway obstruction, decreased thoracic capacity, spina bifida, and scoliosis. Case presentation: We describe a case of a late preterm neonate boy presenting with low Apgar, respiratory distress, and complicated orofacial anomalies that had a poor outcome. His radiographic findings showed mandibular hypoplasia (micrognathia), chest deformity, multiple posterior rib gap defects, and abnormal costotransverse articulation. Based on physical examination and radiologic findings, the diagnosis of CCMS confirmed for the patient. Conclusion: Physicians should always consider the diagnosis of CCMS in all infants with micrognathia and rib-gap defects. These infants need careful respiratory function monitoring. Early airway management improves growth and development. In addition, their physical and psychological development should be assessed regularly. [ABSTRACT FROM AUTHOR]

Pierre Robin sequence (PRS) is characterized by facial abnormalities such as micrognathia, glossoptosis, and upper airway obstruction. Up to 90% of these children will present with cleft palate. Cleft palate is considered a common feature of PRS but is not a mandatory diagnostic characteristic. Premature diagnosis of PRS is prudent to plan and decide earlier on modes of airway management in infants with PRS, which, to date, remains a conundrum. We describe the challenges faced in managing an infant with PRS. We perform a narrative review of treatment options available for children with PRS and advocate for the role of early multidisciplinary teams in managing children with PRS. [ABSTRACT FROM AUTHOR]

Objective: to investigate the ability of mandibular distraction osteogenesis (MDO) to avoid gastrostomy tube (G-tube). Data Sources: PubMed, EBSCOhost, Cochrane, and Embase. Review Methods: We retrospectively reviewed the number of MDO cases performed at our institution for patients with Robin Sequence (RS) over the past 10 years. In our institutional review, patients were excluded if they had a G-tube already placed at the time of surgery. We also performed a systematic review of the literature. Articles were excluded if they did not detail feeding outcomes after MDO, or if MDO was performed on patients that did not have RS. Results: In our systematic review, 12 articles were included that comprised a total of 209 neonates with RS that underwent MDO. A total of 174 (83.3%) patients avoided a G-tube once MDO was performed. A total of 14 patients met the inclusion criteria at our institution. Of the 14 RS patients, 9 (64%) avoided having a G-tube placed and all (14/14) avoided tracheostomy. The average birth weight of patients avoiding a G-tube was 3.11 kg compared to 2.25 kg (P =.045) in the group requiring a G-tube. In the group avoiding a G-tube, the average weight at time of operation was 3.46 kg compared to 2.83 kg (P =.037) in the group requiring a G-tube. Conclusion: MDO may be considered as a surgical option to prevent G-tube placement for neonates with non-syndromic RS who have difficulty with PO feeding but whose airway obstruction is not severe enough to require respiratory support. Based on our institutional experience, a minimum weight of 3.00 kg correlated with higher success rates of PO intake and avoiding a G-tube. [ABSTRACT FROM AUTHOR]

Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships.

Brainstem evoked response audiometry (BERA) is the most established and recommended objective audiometric method for the clinical diagnosis of hearing impairment in high-risk infants. It is unclear whether infants with orofacial clefts meet the criteria for the high-risk group. This retrospective cohort study evaluated the need for diagnostic BERA in infants with cleft palate with or without cleft lip by assessing the predisposition to and diagnosis of congenital hearing impairment. Data from 122 patients treated at a single cleft centre were evaluated. BERA was conducted at the time of palate repair at 4–6 months of age. Clinical follow-up was analysed up to 4 years. The presence of a syndrome was examined as a risk factor for congenital hearing impairment. Among the 122 patients, four had congenital sensorineural or mixed hearing loss requiring hearing aids. All affected patients had syndromes in addition to the cleft. Most patients with elevated hearing thresholds had transient conductive hearing loss. Most suspected sensorineural hearing loss initially diagnosed was refuted. However, a higher incidence of sensorineural hearing loss was found in patients with syndromic clefts, supporting the diagnostic use of BERA with initial surgery only in patients with syndromic clefts. [ABSTRACT FROM AUTHOR]

The phenotypic spectrum of Bruck syndrome has broadened since its first description. Besides its orthopedic manifestations, other findings such as myopathy or cardiac disease have been reported in previous studies. A case is presented with Pierre Robin syndrome and subglottic mass. Because of the clinical picture of congenital high airway obstruction syndrome, emergency tracheotomy was performed upon delivery. An excisional biopsy under direct laryngoscopy was done later. The patient died of congestive heart failure when 8 months old. In conclusion, Bruck syndrome types 1 and 2 may not be phenotypically equivalent and there may be unexpected upper respiratory system findings. [ABSTRACT FROM AUTHOR]

Objective: Assess the impact of prenatal diagnosis of Robin sequence (RS) on parental experience during gestation and early infancy. Design: Prospective case-control study. An online survey was administered via email to 44 parents representing 34 unique patients with RS. Participants: Parents of children diagnosed with RS and who received mandibular distraction at our tertiary care children's hospital. Participants were separated by the timing of RS diagnosis into prenatal and control postnatal groups. Main Outcome Measures: Effects of timing of diagnosis on parents' preparation, caregiver support, education about the condition, stress, and overall mental health. Results: Complete responses were received from 44 parents representing 34 unique patients (50% response rate): prenatal, n = 17; postnatal, n = 27. Prenatal diagnosis improved parents' satisfaction regarding time to prepare for treatment (P =.001), stress of uncertainty about their child's health (P =.018), and stress about the operation(s) their child would need (P =.001). Both the prenatal (82%) and postnatal (78%) groups reported a negative impact on mental health based on diagnosis timing. All parents in the prenatal group preferred having received a prenatal diagnosis and the majority of the postnatal group (85%) would have preferred to have received the diagnosis prenatally. Conclusions: Prenatal diagnosis of RS provided tangible benefits for parents by allowing them to mentally prepare, make plans for delivery and treatment, and become educated about the condition. Parents in both groups reported a negative impact on their mental health based on diagnosis timing and the majority of parents consistently preferred prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Surgical missions are often conducted in outreach areas where facilities are often not as advanced as in an institution. Excellent team coordination, detailed planning, and good communication are necessary for a successful outcome. Unfamiliar work environment, new acquaintances within the team, and language barriers at the mission site are some of the challenges often faced. Careful patient selection is crucial in a mission setup as most complications can be traced back to the preanaesthetic check and preoperative preparedness. We describe airway management strategies (airway assessment, mask ventilation, intubation options, and the postoperative airway plan) contrived by our anaesthesia team at one such surgical mission where four children with Pierre Robin Syndrome and incomplete cleft palate (involving posterior hard palate and complete soft palate)were successfully operated.

The results of a survey of twenty-four neonatal units in the United Kingdom and Ireland are presented. A structured ten-item questionnaire was used, and demonstrated the variation in how infants with RS are diagnosed and managed. Notably, the survey revealed that a minority of infants were diagnosed antenatally. There were significant discrepancies in diagnostic criteria used and 79% of the units referred the patients to tertiary services. A preference for minimally invasive approaches to managing upper airway obstruction, such as a trial of prone positioning before progressing to a nasopharyngeal airway, was reported by 96% of the centers. A narrative review was undertaken which discusses the current practices for diagnosis and early management of Robin sequence (RS). The challenges of antenatal diagnosis, strategies to enhance outcomes through early detection and controversies surrounding the management of neonatal upper airway obstruction associated with RS are included. The results of the survey and our comprehensive review of the literature emphasize that there remains uncertainty regarding the best approach to treating Robin sequence.

Objective : To describe perioperative feeding performance in infants with Robin sequence (RS) who underwent mandibular distraction osteogenesis (MDO). Design : A retrospective study of infants that underwent MDO from May 2010 to December 2019. Setting : Tertiary pediatric hospital. Patients : A total of 40 patients underwent MDO and 20 met inclusion criteria. Of the included infants, 6 had an associated syndrome and 80% were male. Main Outcome Measures : Time to full oral feeds, rate of G-tube placement, and change in weight percentile following MDO. Results : Average oral intake prior to MDO was 22.1% of individual goal feeds. Among the 15 (75%) children that did not require G-tube placement, mean time to full oral feeds after MDO was 11 days ± 5.7 days, with 80% of infants reaching full oral feeds within 2 weeks after extubation. The proportion of G-tube placement in patients with a syndrome was higher than in isolated RS (−0.6; 95% CI: −1.0, −0.2). Mean percentages of weight-for-age percentile decreased during the first 3 months after the procedure. This was followed by a mean upturn in weight starting after the third month after MDO with a recovery to preoperative mean weight-for-age percentiles by 6 months after surgery. Conclusions : This study suggests that infants with RS may achieve full oral feeds despite poor feeding performance before MDO. Infants with syndromic RS are more likely to require G-tube. These findings may be used to inform G-tube discussion and offer a timeline to work toward goal oral feeds for infants with RS after MDO. [ABSTRACT FROM AUTHOR]

Objective: Robin sequence (RS) consists of micrognathia and glossoptosis that result in upper airway obstruction (UAO). In RS patients who undergo tracheostomy, long-term goals include natural decannulation (ND) without further surgical airway intervention. The objective of this study was to identify long-term trends in the rate and length of time to ND. Methods: Retrospective chart review on 144 patients with RS treated from 1995 to 2020 at a pediatric tertiary care center. Patients were grouped by year of tracheostomy. Demographic data, UAO management, postoperative care, complications, and time to decannulation were recorded. Results: Thirty-six patients met the inclusion criteria. Tracheostomy was performed at a median age of 45.5 days. 19 (53%) patients experienced ND at a median time of 66.1 months. ND rate was higher in non-syndromic patients (93% non-syndromic vs 27% syndromic; P <.0001) and during the first study period (1995-2006: 78%, 2007-2020: 28%; P =.003). Cox proportional-hazard regression demonstrated that white race [aHR 0.15 (0.03-0.8); P =.023] and higher birthweight [aHR 0.9 (0.8-0.98); P =.018] were associated with a higher likelihood of ND while a syndromic diagnosis had a negative association with ND [aHR 12.5 (3.3-50.0); P <.001]. Conclusions: Our study documented that ND in patients with RS who underwent tracheostomy was significantly associated with ethnicity, birthweight, and syndromic status. The negative impact on successful ND was most observed in patients with syndromic associations. Additionally, ND rates are lower in the 2007 to 2020 subgroup. We suspect this is because alternative management techniques such as tongue lip adhesion and mandibular distraction osteogenesis became primary surgical treatment in severe RS upper airway obstruction at our institution starting in 2007. [ABSTRACT FROM AUTHOR]

Surgical missions are often conducted in outreach areas where facilities are often not as advanced as in an institution. Excellent team coordination, detailed planning, and good communication are necessary for a successful outcome. Unfamiliar work environment, new acquaintances within the team, and language barriers at the mission site are some of the challenges often faced. Careful patient selection is crucial in a mission setup as most complications can be traced back to the preanaesthetic check and preoperative preparedness. We describe airway management strategies (airway assessment, mask ventilation, intubation options, and the postoperative airway plan) contrived by our anaesthesia team at one such surgical mission where four children with Pierre Robin Syndrome and incomplete cleft palate (involving posterior hard palate and complete soft palate)were successfully operated. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the mid-term effect of MDO in children with Robin sequence (RS). In this case series, 13 patients with RS who underwent MDO were followed up for more than 5 years. Data were collected using clinical history and physical examination. Polysomnography was performed and endoscopic evaluations of the airway was performed if patients still presented obstructive signs of upper airways and/or dysphagia. The patients' clinical signs improved in the mid-term after versus before MDO (inspiratory noise, 92,3% vs 30,8%; apnea, 84,6% vs 7,7%; cyanosis, 76,9% vs 0%; desaturations, 69,2% vs 0%; and suprasternal/intercostal retractions, 61,5% vs 0%; p < 0.05). Statistically significant improvement was noted in the following polysomnographic parameters evaluated in the pre and postoperative mid-term: apnea-hypopnea index, total sleep time and desaturation index (p < 0.05). Within the limitations of the study it seems that MDO is an effective surgical option for children with RS, not only in the short term as previously demonstrated, but also in the mid-term. [ABSTRACT FROM AUTHOR]

Objective: To investigate the subjective risk for obstructive sleep apnea (OSA) in adolescents and young adults with isolated Robin sequence (IRS). Additionally, to investigate the association of OSA risk with respiratory signs/symptoms, and retrognathia. Design: Prospective, observational, and cross-sectional study. Setting: Tertiary reference hospital for the rehabilitation of craniofacial anomalies. Participants: Adolescents and adults (n = 30) with IRS were clinically evaluated and screened through the Berlin Questionnaire (BQ) and Respiratory Symptoms Questionnaire. The maxillomandibular relationship was assessed on lateral cephalograms of those that reached skeletal maturity (n = 13). Polysomnography (PSG) was performed in a subgroup of 4 individuals. Results: The mean age of the sample was 18.2 (±3.4) years, 17 (56.7%) were adolescents (14-19 years), and 16 were (53.3%) female, all presented a repaired cleft palate. Clinical Parameters: Systemic arterial pressure (118.0 ± 4.1/76.3 ± 4.9 mmHg), body mass index (BMI) (20.9 ± 2.8 kg/m2), neck (33.2 ± 2.3 cm), and waist circumferences (72.0 ± 5.8 cm) were within normal ranges. A skeletal class I pattern was observed in 61.5% of the participants while a class II was seen in 15.4% of them. A high risk for OSA was detected in 16.7%, and it was associated with nasal obstruction, snoring and drowsiness, and a skeletal class II pattern (P ≤.05). One patient presented with mild OSA (apnea–hypopnea index [AHI] = 10.1 events/hour) at the PSG exam. Conclusions: A high risk for OSA can be observed with a moderate frequency among adolescents and young adults with IRS, especially among those who are concurrently suffering from nasal obstruction, snoring and retrognathia. [ABSTRACT FROM AUTHOR]

Background: This study characterizes the potential loss of velar length in patients with a wide cleft and rescue of this loss of domain by local flap reconstruction, providing anatomic evidence in support of primary lengthening of the soft palate during palatoplasty. Methods: A retrospective review was conducted of all patients with a cleft palate at least 10mm in width, who underwent primary palatoplasty with a buccal flap prior to 18 months of age over a 2-year period. All patients underwent primary palatoplasty with horizontal transection of the nasal mucosa, which was performed after nasal mucosa repair, but prior to muscular reconstruction. The resulting palatal lengthening was measured and the mucosal defect was reconstructed with a buccal flap. Results: Of the 22 patients included, 3 (13.6%) had a history of Pierre Robin sequence, and 5 (22.7%) had an associated syndrome. No patients had a Veau I cleft, 7 (31.8%) had a Veau II, 12 (54.5%) had a Veau III, and 3 had (13.6%) a Veau IV cleft. All patients had a right buccal flap during primary palatoplasty. The mean cleft width at the posterior nasal spine was 10.6 ± 2.82mm, and mean lengthening of the velum after horizontal transection of the nasal mucosa closure was 10.5 ± 2.23mm. There were 2 (9.1%) fistulas, 1 (4.5%) wound dehiscence, 1 (4.5%) 30-day readmission, and no bleeding complications. Conclusions: Patients with a wide cleft palate have a potential loss of 1cm velar length. The buccal flap can rescue the loss of domain in palatal length, and potentially improve palatal excursion. [ABSTRACT FROM AUTHOR]

Objective: Describe the intelligence quotient (IQ) of children with Pierre Robin sequence (PRS). Design: Prospective cohort study. Setting: Neurodevelopmental follow-up clinic within a hospital. Patients: Children with PRS (n = 45) who had been in the Neonatal Intensive Care Unit (NICU) were classified by a geneticist into 3 subgroups of isolated PRS (n = 20), PRS-plus additional medical features (n = 8), and syndromic PRS (n = 17) based on medical record review and genetic testing. Main Outcome Measure: Children with PRS completed IQ testing at 5 or 8 years of age with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III) or Fourth Edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) or Fifth Edition (WISC-V). Results: IQ scores were more than 1 to 2 standard deviations below the mean for 36% of the overall sample, which was significantly greater compared to test norms (binomial test P =.001). There was a significant association between PRS subtype and IQ (Fisher's exact P =.026). While only 20% of children with isolated PRS were within 1 standard deviation below average and 35% of children with syndromic PRS were below 1 to 2 standard deviations, 75% of PRS-plus children scored lower than 1 to 2 standard deviations below the mean. Conclusion: PRS subgroups can help identify children at risk for cognitive delay. The majority of children with PRS-plus had low intellectual functioning, in contrast to the third of children with syndromic PRS who had low IQ and the majority of children with isolated PRS who had average or higher IQ. [ABSTRACT FROM AUTHOR]

The purpose of this article is to report the author's technique for using patient-specific distractors for customized distraction osteogenesis of the mandible in patients with Pierre Robin sequence and upper airway obstruction. The advantages of virtual planning and patient-specific plates in other aspects of craniomaxillofacial surgery, such as orthognathic and reconstructive surgery, have been reported previously. Similar to patient-specific plates, the theorized advantages of patient-specific distractors in infants with Robin sequence and upper airway obstruction include increased accuracy, decreased operating time, and less morbidity to vital anatomic structures such as the inferior alveolar nerve and developing tooth buds. This technique is novel in using patient-specific distractors in the craniomaxillofacial skeleton. [ABSTRACT FROM AUTHOR]

Robin sequence (RS), a congenital disorder of jaw maldevelopment and glossoptosis, poses a substantial healthcare burden and has long-term health implications if airway obstruction is suboptimally treated. This study describes the global birth prevalence of RS and investigates whether prevalence estimates differ by geographical location, ethnicity or study data source (registry versus non-registry data). The protocol was prospectively registered with PROSPERO. Databases were searched using keywords and subject terms for “Robin sequence”, “epidemiology”, “incidence” and “birth prevalence”. Meta-analysis was performed fitting random effects models with arcsine transformation. From 34 eligible studies (n=2722 RS cases), pooled birth prevalence was 9.5 per 100 000 live births (95% CI 7.1–12.1) with statistical heterogeneity. One third of studies provided a case definition for RS and numerous definitions were used. A total of 22 countries were represented, predominantly from European populations (53% of studies). There was a trend towards higher birth prevalence in European populations and lower prevalence from registry-based studies. Only two studies reported ethnicity. This study indicates that RS occurs globally. To investigate geographical differences in prevalence, additional studies from non-European populations and reporting of ethnicity are needed. Heterogeneity of estimates may be due to variable diagnostic criteria and ascertainment methods. Recently published consensus diagnostic criteria may reduce heterogeneity among future studies. [ABSTRACT FROM AUTHOR]

Introduction: Pierre Robin syndrome is a malformative sequence associating retrognathism, glossoptosis and a median cleft palate which is usually large. This poses the problem of its therapeutic management. Purpose: To show the approach of the Stomatology and Maxillofacial Surgery Department of the Mohammed VI University Hospital in the management of cleft palate in Pierre Robin syndrome.This was a retrospective study, covering 5 years, which allowed us to include 7 cases of cleft palate in Pierre Robin syndrome. Our study parameters were epidemiological, clinical, therapeutic and evolutionary. Results: The average age of our patients, at the time of the 1st consultation, was 4 months. There was a slight male predominance with a sex ratio = 1.3. The patients presented a U-shaped cleft in 57.1% of cases, and a V-shaped cleft in 42.9% of cases. Three patients underwent a one-stage closure by velopalatoplasty using the Von Langenbeck technique. Four patients underwent a 2-stage closure, i.e., intravascular veloplasty in the first stage, followed by closure of the residual cleft palate in the second stage. The results were satisfactory. A palatal fistula was noted in 42.8% of cases, which was managed secondarily. Conclusion: The management of cleft palate in Pierre Robin syndrome is a real challenge for the maxillofacial surgeon.

Objective: To characterize the prevalence and presentation of laryngomalacia and efficacy of supraglottoplasty (SGP) in a cohort of patients with Pierre Robin Sequence (PRS). Design: Retrospective cohort study. Setting: Tertiary-care children's hospital. Patients, Participants: Consecutive patients with PRS born between January 2010 and June 2018. Main Outcome Measures: Chart review included demographics, comorbid airway obstruction including laryngomalacia, timing of surgical interventions, clinical symptoms, sleep study data, and modified barium swallow study data. Results : 126 patients with PRS were included; 54% had an associated syndrome, 64% had an overt cleft palate, and 22% had a submucous cleft palate. 64/126 were noted to have laryngomalacia (51%). Patients with concurrent PRS and laryngomalacia were significantly more likely to have submucous cleft palate (P =.005) and present with aspiration with cough (P =.01) compared to patients with PRS without laryngomalacia. Patients with concurrent laryngomalacia and PRS showed a significant decrease in apnea–hypopnea index (AHI) and obstructive AHI (OAHI) after mandibular distraction, with a median AHI and OAHI improvement of 22.3 (P =.001) and 19.8 (P =.002), respectively. Patients who underwent only SGP did not show significant improvement in these parameters (P =.112 for AHI, P =.064 for OAHI). Conclusions : The prevalence of laryngomalacia in our PRS cohort was 51%. Patients with PRS and laryngomalacia are more likely to present with overt aspiration compared to patients with PRS without laryngomalacia. These data support that laryngomalacia does not appear to be a contraindication to pursuing MDO. [ABSTRACT FROM AUTHOR]

Objective: Prior research suggests that children with cleft palate (CP) are at increased risk of obstructive sleep-disordered breathing (SDB). However, few studies differentiate the effects of CP repair on SDB based on syndrome status. The goal of this study was to evaluate differences in SDB after palatoplasty among children with nonsyndromic CP, syndromic CP, and isolated Robin sequence (RS). Design: Retrospective chart review. Setting: Tertiary academic children's hospital. Patients/Participants: A total of 145 children who underwent primary CP repair from 2014 to 2021. Main Outcome Measure: Post-palatoplasty SDB is defined as parent-reported symptoms and/or evidence of obstructive sleep apnea (OSA). Results: Median age at palatoplasty was 11.1 [IQR 10.2-13.6] months. Most patients (61.4%) had nonsyndromic CP, 26.9% had a syndrome, and 11.7% had RS. Children with syndromic CP and RS had more post-palatoplasty SDB symptoms (56.4% vs 58.8% vs 30.3%, P =.006) and higher rates of OSA (25.6% vs 29.4% vs 5.6%, P =.001) compared to children with nonsyndromic CP after palatoplasty. Children with syndromic CP and RS had nearly 3 to 4 higher odds of post-palatoplasty SDB than children with nonsyndromic CP (adjusted odds ratio [aOR] 2.88, 95% CI 1.29–6.47, P =.010; aOR 3.73, 95% CI 1.19–11.70, P =.024). Conclusion: This study showed that children with CP experience higher rates of SDB after palatoplasty than the general pediatric population. Within the cohort, children with syndromic CP and isolated RS were more likely to have obstructive sleep disorders than nonsyndromic children after palatoplasty. Clinicians should counsel caregivers accordingly and closely monitor these groups for SDB after palate repair. [ABSTRACT FROM AUTHOR]

The Tübingen Palatal Plate (TPP) is a minimally invasive yet highly effective functional orthodontic treatment for upper airway obstruction in infants with Robin Sequence (RS). It consists of a palatal plate to cover the cleft and a velar extension that shifts the root of the tongue forward. We review our practical experience with this approach. First, upon admission, our local orthodontists perform an (3-D) intraoral scan of the maxilla. Based on the scan data, the TPP is manufactured in a semi-digital workflow. The length and angulation of its extension is checked via awake laryngoscopy and the effectiveness confirmed by a sleep study. Plates are kept in place by adhesive cream. When inserting the TPP, the tip of the tongue must be visible. Next, metal fixation bows should be secured to the forehead using tape and elastic bands. Plates are removed daily for cleaning, and the oral mucosa is then checked for pressure marks. Feeding training (initially only via finger feeding) may even start before plate insertion. Breathing often normalizes immediately once the plate is inserted. For isolated RS, we have never had to perform a tracheostomy. This has largely been possible through our highly dedicated and competent team, particularly the nursing staff, and the early involvement of parents. [ABSTRACT FROM AUTHOR]

Mandibular Distraction Osteogenesis (MDO) is now the preferred procedure to alleviate airway obstruction in infants with severe Robin Sequence (RS). However, there have been very few studies investigating complications related to MDO surgery performed on patients affected by isolated RS. In this study, age at distraction, weight at distraction, preoperative intubation, repeat MDO and complications associated with MDO were included as variables. Minor, moderate and major problems were evaluated and recorded as surgical site infections (SSI), injuries to the facial nerve, self-extinction hypertrophic scars, temporomandibular joint ankylosis, device failures, early ossification and fibrous non-union. One hundred and fifty one patients with isolated RS were included. At distraction, the mean age was 72 days (12–540 days) and the mean weight was 4.05 kg (2.4–12.2 kg). Only one patient needed tracheostomy after MDO, and none required further distraction. Ultimately, the complication rate was 15.23%, and there was a total of 7.95% minor, 9.27% moderate and 0% major complications. Minor incidents included surgical site infection (SSI) managed with antibiotics taken orally (n = 8), neuropraxia in the VII cranial nerve (CN) (n = 1), and hypertrophic scarring (n = 3). Incidents reported as moderate were SSIs managed with intravenous antibiotics (n = 9), incision and drainage (n = 3) and self-extubation (n = 2). There was no case of TMJ ankylosis. There were no cases of early or premature ossification, fibrous non-union and device fracture. In conclusion, MDO is an effective and appropriate management technique for infants with isolated RS and severe airway obstruction. Infections at the surgery site accounted for the vast majority of the complications. Further investigations may be needed to determine the long-term consequences of MDO. [ABSTRACT FROM AUTHOR]

Dysphagia in Robin Sequence can be present in varying degrees, requiring multidisciplinary management and specific swallowing assessment by a specialist. Most studies published to date have evaluated only respiratory outcomes, and the available evidence on the improvement of swallowing is questionable. To conduct a systematic review and meta-analysis of studies evaluating swallowing in children with Robin Sequence before and after airway clearance procedures. The research question was developed based on the PICO strategy. The literature search was performed in electronic databases and gray literature. Studies were selected by 3 independent reviewers. The risk of bias and level of evidence of the studies were assessed. A proportion meta-analysis was performed to calculate the prevalence of dysphagia after airway clearance procedures. The search identified 4938 studies, 5 of which were included. All studies had limitations in terms of design and sample size. The prevalence of dysphagia after airway clearance was obtained by analyzing treatment subgroups: mandibular distraction osteogenesis, mandibular distraction osteogenesis + tracheostomy tube, and nasopharyngeal tube. Clinical and/or instrumental assessment was assessed by a swallowing specialist. The meta-analysis was precluded by the limitations of the studies, especially regarding sample size, which affected the accuracy of the findings. Dysphagia remained unresolved in 55% of children (95% CI 1–99%). The methodological quality of the studies indicated a high risk of bias and very low level of evidence. It was not possible to confirm that airway clearance techniques used in Robin Sequence improve dysphagia. [ABSTRACT FROM AUTHOR]

Disease summary: A diagnosis of Pierre Robin sequence (PRS) is established when a patient exhibits the three clinical hallmarks of micrognathia (small mandible), glossoptosis (backward downward displacement of the tongue base) and airway obstruction present from birth. Cleft palate commonly occurs, but is not a prerequisite for a diagnosis. Pierre Robin sequence may be isolated (20-40 %) or associated with a syndrome, the commonest being Stickler, foetal alcohol, Treacher-Collins and velocardiofacial syndrome. The anatomical features cause a variable degree of airway obstruction and patients may present with stridor, respiratory distress, cyanosis and signs of obstructive sleep apnoea (OSA). Patients may also exhibit other airway pathology such as laryngomalacia and subglottic stenosis. Patients are at risk of inadequate nutrition, aspiration and gastro oesophageal reflux disease. Incidence varies between 1:5,000 to 1:85,000, the range a reflection of the variable clinical presentation. [ABSTRACT FROM AUTHOR]

Since 1920s, a triple combination of micrognathus, drooping tongue and upper airway obstruction has been recognized as Pierre Robin Syndrome (PRS).It occurs alone or in combination with other syndromes, such as first/second branchial arch syndrome and other related syndromes.PRS sequence is clinically associated with dyspnea and feeding difficulties in neonates.Severe PRS cases may die from respiratory obstruction at birth.Thus an early diagnosis is vital during fetal period so that timely treatment may be offered after birth.Therefore more objective diagnostic rationales are required for diagnosing PRS.This review focused upon recent applications of computed tomography (CT) reconstruction and three-dimensional digital technology for an early diagnosis of PRS sequence sign. [ABSTRACT FROM AUTHOR]

We recently published the 3-month follow-up of 2 neonates with Robin sequence whose mandibular hypoplasia and restricted airway were successfully treated with an orthodontic airway plate (OAP) without surgical intervention. Both infants were successfully weaned off the OAP after several months of continuous use. We present the course of OAP treatment in these patients with a focus on breathing, feeding, and facial growth during their first year of life. Both infants demonstrated stable mandibular projection, resolution of obstructive sleep apnea, and normal development. [ABSTRACT FROM AUTHOR]

Background: Controversy remains regarding optimal management of Pierre Robin sequence (PRS). The goal of this study was to compare airway and feeding outcomes in infants with PRS who underwent surgical intervention, specifically mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA), or who had conservative management (CM) without surgery. Methods: All consecutive patients treated for PRS at a pediatric academic medical center, with at least one year follow-up, were included. Patients who underwent tracheostomy as an index procedure were excluded. Patients were divided into those who underwent MDO, TLA or CM. Feeding status and data from initial and follow-up polysomnograms were collected. Comparisons between groups were made using the Kruskal-Wallis test, followed by Mann-Whitney pairwise comparison with a Bonferroni correction, when appropriate. Results: 67 neonates were included. 19 underwent TLA, 29 underwent MDO and 19 underwent CM. The proportions of syndromic patients were similar between groups. Patients undergoing CM had the lowest baseline AHI (9.1), but there were no significant differences between TLA (20.1) and MDO (25.4). At follow-up, the three groups had similar mean AHI (MDO 1.3, TLA 4.2, CM 4.5). A similar proportion of patients achieved AHI 5 or less (TLA 89.5%, MDO 96.6%, CM 84.2%). At one year, there were no significant differences in weight percentiles or in risk of failure-to-thrive between groups. One patient from the TLA group required a tracheostomy. Conclusion: The three treatment modalities achieved high airway and feeding success rates. All three modalities should have a place in the armamentarium of the craniofacial surgeon. [ABSTRACT FROM AUTHOR]

Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS). Leveraging a human stem cell differentiation model, we identify two clusters of enhancers within the PRS-associated region that regulate SOX9 expression during a restricted window of facial progenitor development at distances up to 1.45 Mb. Enhancers within the 1.45 Mb cluster exhibit highly synergistic activity that is dependent on the Coordinator motif. Using mouse models, we demonstrate that PRS phenotypic specificity arises from the convergence of two mechanisms: confinement of Sox9 dosage perturbation to developing facial structures through context-specific enhancer activity and heightened sensitivity of the lower jaw to Sox9 expression reduction. Overall, we characterize the longest-range human enhancers involved in congenital malformations, directly demonstrate that PRS is an enhanceropathy, and illustrate how small changes in gene expression can lead to morphological variation.

IntroductionThe Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS.MethodsWe explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion.ResultsOur systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS.ConclusionSpinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management.

Pierre Robin sequence (PRS) is an inherited disorder that affects one in between 8,500 and 14,000 people and is characterized by a triad of clinical signs. These include micrognathia, glossoptosis and obstruction of the upper airway, typically associated with palatal cleft. PRS has also been associated with various ocular complications, including high congenital myopia, congenital glaucoma, and retinal detachment. Because of the clinical importance of PRS, it is critical to illustrate the features of the Robin sequence to clearly define its primary and secondary clinical signs. We describe a patient with PRS who developed keratoconus as a rare manifestation of the disease and its management.

Pierre Robin Sequence (PRS) is a congenital condition characterized by micrognathia, glossoptosis, and cleft palate that presents with airway obstruction and developmental delay with or without other congenital anomalies. These patients’ anesthesia management is challenging because of difficult ventilation and intubation. Regional anesthesia methods should be considered for these patients on a case-by-case basis. This report presents primary use of regional anesthesia for circumcision of a 9-year-old boy with PRS.

Key Clinical Message: Children with Pierre Robin syndrome (PRS) often have trouble breathing and eating as soon as they are born. If conservative therapy fails to alleviate airway obstruction, surgical surgery may be considered. Patients with PRS require multidisciplinary approaches for treatment. Pierre Robin syndrome is a common craniofacial abnormality that causes glossoptosis and blockage of the upper airway. This renders it difficult to feed, which leads to severe malnutrition. This condition is also often marked by an absence of a soft palate. We mention a newborn with Pierre Robin syndrome with the absence of a soft palate and pneumonia complications, whose impending respiratory failure was treated successfully. To solve the complex problems that these babies and their families are facing, a multidisciplinary approach is needed. [ABSTRACT FROM AUTHOR]

The aims of this cohort study were to compare the mandibular morphology between patients with Robin sequence (RS) and controls, and to examine the effects of mandibular distraction osteogenesis (MDO) using different vectors. Measurements of the mandibles of 80 patients with RS and 46 controls aged< 90 days were made using computed tomography. The data were compared among isolated RS patients (n = 58), sy n dromic RS patients (n = 22), a n d controls. Patients with RS exhibited significantly shorter ramus and body lengths and larger symphyseal angles than controls (all P < 0.001). P atients with isolated RS had shorter body lengths (P < 0.001), while syndromic patients had shorter ramus and body lengths (both P < 0.001) than controls. Seventy RS patients underwent MDO. Pre-MDO (n = 37) and post-MDO (n = 29) mandibular measurements were compared between patients undergoing MDO with a vertical vector and those undergoing MDO with a horizontal vector. Polysomnography data from part of the cohort highlighted the effectiveness of both vectors. MDO with a horizontal vector conferred 11% and 36% increases in ramus and body length, respectively, while these increases were 34% and 27.5%, respectively, with a vertical vector. MDO with a vertical vector was effective in lengthening ramus and body components and should be considered in the presence of ramus hypoplasia. [ABSTRACT FROM AUTHOR]

Objective: Robin Sequence (RS), characterized by micrognathia, glossoptosis, and upper airway obstruction, is an increasingly recognized diagnosis. An effective surgical intervention is mandibular distraction osteogenesis (MDO). This study analyzes published evidence regarding facial nerve dysfunction (FND) associated with MDO. Design and Setting: According to PRISMA guidelines, a systematic review was carried out with databases queried in June 2019 using MESH terms, or equivalent terms, as follows: "distraction osteogenesis" and "Robin Sequence". A review of original Spanish and English articles, were included. Outcome measures included the prevalence of FND; the affected branches; the rate of permanent vs. transient FND; the use of an internal vs. external device; the daily distraction rate; and finally, the overall distraction length. Subsequently, a meta-analysis was conducted to collate results regarding the prevalence of FND and the factors associated with it. Results: Of 239 unique studies identified, 19 studies with 729 patients met inclusion criteria; 52 patients developed FND after MDO. A random-effects meta-analysis yielded a pooled prevalence of FND of 6.40%, with moderately heterogeneous studies (I2 = 41%, τ2 = 0.006). Marginal mandibular nerve involvement was most commonly noted. Nine studies reported transient FND, six permanent, one both, and two unspecified. Internal distractors were used in 8 studies and external in 3 and both in 2. Distraction rate was 1.00 to 2.00 mm/day and total distraction length ranged from 13.00 to 22.3 mm. Sample size was the only parameter inversely associated with rate of FND (p = 0.04). Conclusion: This analysis of FND associated with MDO for patients with RS demonstrates a lack of consistent documentation. MDO-associated FND does not appear to be uncommon, and permanent dysfunction can occur. This review underscores the importance of thorough documentation to elucidate the mechanism of FND. [ABSTRACT FROM AUTHOR]

The goal of this study was to explore the availability of diagnostic and treatment options for managing upper airway obstruction (UAO) in infants with Robin Sequence (RS) in Europe. Countries were divided in lower- (LHECs, i.e., PPP per capita < $4000) and higher-health expenditure countries (HHECs, i.e., PPP per capita ≥ $4000). An online survey was sent to European healthcare professionals who treat RS. The survey was designed to determine the availability of diagnostic tools such as arterial blood gas analysis (ABG), pulse oximetry, CO2 analysis, polysomnography (PSG), and sleep questionnaires, as well as to identify the used treatment options in a specific center. Responses were received from professionals of 85 centers, originating from 31 different countries. It was equally challenging to provide care for infants with RS in both LHECs and HHECs (3.67/10 versus 2.65/10, p = 0.45). Furthermore, in the LHECs, there was less access to ABG (85% versus 98%, p = 0.03), CO2 analysis (45% versus 70%, p = 0.03), and PSG (54% versus 93%, p < 0.01). There were no significant differences in the accessibility concerning pulse oximetry, sleep questionnaires, home saturation monitoring, nasopharyngeal tubes, Tuebingen plates, and mandibular distraction. Conclusion: This study demonstrates a large difference in available care for infants with RS throughout Europe. LHECs have less access to diagnostic tools in RS when compared to HHECs. There is, however, no difference in the availability of treatment modalities between LHECs and HHECs. What is Known: • Patients with Robin sequence (RS) require complex and multidisciplinary care. They can present with moderate to severe upper airway obstruction (UAO). There exists a large variety in the use of diagnostics for both UAO treatment indications and evaluations. In most cases, conservative management of UAO in RS is sufficient. Patients with UAO that persist despite conservative management ultimately need surgical intervention. To determine which intervention is best suitable for the individual RS patient, the level of UAO needs to be determined through diagnostic testing. • There is a substantial variation among institutions across Europe for both diagnostics and treatment options in UAO. A standardized, internationally accepted protocol for the assessment and management of UAO in RS could guide healthcare professionals in the timing of assessment and indications to prevent escalation of UAO. Creating such a protocol might be a challenge, as there are large financial differences between countries in Europe (e.g., health expenditure per capita in purchasing power parity in international dollars ranges from $600 to over $8500). What is New: • There is a substantial variation in the availability of objective diagnostic tools between European countries. Arterial blood gas analysis, CO2 analysis and polysomnography are not equally accessible for lower-healthcare expenditure countries (LHECs) compared to higher-healthcare expenditure countries (HHECs). These differences are not only limited to availability; there is also a difference in quality of these diagnostic tools. Surprisingly, there is no difference in access to treatment tools between LHECs and HHECs. • There is national heterogeneity in access to tools for diagnosis and treatment of RS, which suggests centralization of health care, showing that specialized care is only available in tertiary centers. By centralization of care for RS infants, diagnostics and treatment can be optimized in the best possible way to create a uniform European protocol and ultimately equal care across Europe. Learning what is necessary for adequate monitoring could lead to better allocation of resources, which is especially important in a low-resource setting. [ABSTRACT FROM AUTHOR]

Background: Pierre Robin Sequence (PRS) is characterized by micrognathia, glossoptosis, and upper airway obstruction. Early recognition and appropriate perinatal management is crucial for optimizing outcomes. This study aimed to evaluate 20-week fetal ultrasounds to determine if specific mandibular measurements could predict PRS diagnosis and disease severity. Methods: A retrospective case-control study of 48 patients with PRS and gender-matched controls was performed. Medical records were reviewed for respiratory and surgical interventions. Three parameters to assess micrognathia were measured on mid-sagittal profile ultrasound images: frontal nasal-mental angle (FNMA), facial-maxillary angle (FMA), and alveolar overjet. Student's t-test and univariate logistic regression was performed. P ≤ 0.05 was considered statistically significant. Results: Patients with PRS demonstrated a significantly smaller mean FNMA compared to the control group, 129.3 ± 8.6° and 137.4 ± 3.2°, respectively (p < 0.0001), as well as significantly smaller mean FMA, 63.2 ± 9.2° and 74.8 ± 6.1°, respectively (p < 0.0001). The PRS group also demonstrated significantly larger mean alveolar overjet compared to the control group, 3.9 ± 1.4 mm and 2.1 ± 0.9 mm, respectively (p < 0.0001). The odds of respiratory intervention increased among cases when FMA was <68°. Additionally, there was a significant difference in median overjet between patients with PRS who did and did not require respiratory intervention. Conclusions: Mandibular features on the 20-week ultrasound can be measured to predict diagnosis and severity of PRS. This is an important first step to prepare for potential respiratory intervention at delivery to minimize perinatal hypoxia. Alveolar overjet, previously not described in prenatal ultrasound literature, is measurable and has utility in prenatal screening for PRS, as do FMA and FNMA. [ABSTRACT FROM AUTHOR]

Femoral facial syndrome (FFS) is a rare condition which may present with hypoplasia or aplasia of the femora and unusual facies characterized by long philtrum, thin upper lip and micrognathia. We present the case of a ten-month old infant with FFS who had retroglossal obstruction and who was treated with a pre-epiglottic baton plate. The pre-epiglottic baton plate can be a simple, non-invasive and effective tool for the clinical management of syndromic patients with mild-to-moderate upper airway obstruction due to micrognathia. [ABSTRACT FROM AUTHOR]

Objective : To evaluate orthodontic care for patients with craniofacial anomalies (CFA) by identifying orthodontic residents' preparedness to treat certain conditions and willingness to receive more training in CFA. Material and Methods : A 12-question survey was sent through the American Association of Orthodontics (AAO) organization to orthodontic residents. Questions were primarily designed to obtain information on the frequency with which they dealt with patients with CFA in their training, specific craniofacial conditions that orthodontic residents feel comfortable treating. Results : A total of 150 participants out of 1066 responded. Of the 150 responses, 35% were first-year residents, 43% second year, and 22% were third-year residents. Thirty nine percent of residents saw 3 or more CFA patients during their residency followed by 24% that saw no patients with CFA. Forty five percent reported that 1 to 3 hours of lecture time was devoted to CFA per month. Sixty percent felt their training in CFA was not sufficient to feel comfortable treating these patients in practice. Specifically, 62% felt comfortable treating Down syndrome, 84% unilateral cleft lip and/or palate, and 64% bilateral cleft lip and/or palate, while the majority did not feel comfortable treating Pierre Robin sequence (68%), Cleidocranial dysplasia (65%), Crouzon syndrome (75%), Pfeiffer syndrome (80%), Treacher Collins syndrome (76%), Apert syndrome (76%), CHARGE syndrome (84%), and DiGeorge sequence (84%). Seventy eight percent of residents reported that they would like more training in treating craniofacial. Conclusions : Orthodontic residents did not feel comfortable treating patients with CFA. Majority of the residents felt that they would like to learn more about CFA. [ABSTRACT FROM AUTHOR]