Pierre Robin Sequence Patients Research Articles

Growth Patterns of the Maxillomandibular Complex in Preadolescent Patients With Pierre-Robin Sequence Using Cluster Analysis and Longitudinal Follow-Up Cephalometric Data.

To investigate the growth patterns of the maxillomandibular complex in preadolescent patients with Pierre-Robin sequence (PRS). The samples consisted of 20 preadolescent PRS patients who had cleft palate and did not undergo growth-modification therapy or surgical intervention [6 boys and 14 girls; mean age of lateral cephalograms taken, 8.8 y (T1) and 13.7y (T2)]. According to k-means cluster analysis, four clusters were defined over 3 major groups at T1: (1) Both very retrusive maxilla and mandible group: Cluster-4 [n=4, very large gonial angle, very low facial height ratio (FHR)] and Cluster-1 (n=5, small gonial angle, normal FHR); (2) Retrusive maxilla and very retrusive mandible group (Cluster-3, n=7, normal gonial angle, very low FHR); and (3) Both normal maxilla and mandible group (Cluster-2, n=4, very large gonial angle, low FHR). Seven angular and ratio variables [sella-nasion-A point (SNA), sella-nasion-B point (SNB), A point-nasion-B point (ANB), saddle angle, gonial angle, mandibular-body-length/anterior-cranial-base-length (MBL/ACBL), and FHR] at T1 and T2 and growth change from T1 to T2 were investigated. At T1, SNA, SNB, saddle angle, gonial angle (all P<0.05), and FHR (P<0.01) showed significant difference among 4 clusters. At T2, SNA, SNB and gonial angle (all P<0.05) still showed significant difference among 4 clusters. During T1 to T2, there was no significant change in variables at each cluster except an increase in MBL/ACBL in Cluster-1 and FHR in Cluster-3 (all P<0.05). Preadolescent PRS patients exhibited diverse skeletal phenotypes at T1, which did not change significantly from their original skeletal patterns by growth during T1 to T2.

Conservative Airway Management Successful in Majority of Infants With Pierre-Robin Sequence at Queensland Children's Hospital: A Retrospective Review.

Pierre-Robin Sequence (PRS) is a congenital abnormality characterized by micrognathia, glossoptosis, and variable severity upper airway obstruction. Clear management algorithms are lacking, particularly the indications for surgical versus nonsurgical intervention. The authors reviewed the management of these children in Queensland. All children diagnosed with PRS at Queensland Children's Hospital from April 2014 to October 2019 were identified (n=45), and their charts were retrospectively reviewed. Three management patterns emerged: prone/lateral positioning, nasopharyngeal airway (NPA) use, and surgery (tracheostomy or mandibular distraction). Most children (n=30; 67%) were managed successfully nonsurgically with an NPA (median age of insertion 0.25 mo, median duration 5.0 mo). Of these, 12 patients (40%) also required supplemental oxygen. The median age of NPA cessation was 5.5 months, with oxygen therapy ceasing at a median 8.25 months, upon which no further support was required. The remaining majority (n=13; 29%) of children were managed without an NPA, using positioning alone (10/13; 77%) or positioning combined with supplemental oxygen (1/13), CPAP (1/13), or both adjunct measures (1/13). Only 2 patients underwent surgical intervention. Feeding supplementation using nasogastric tube was necessary in 78% of patients for a median duration of 4 months. Cleft palate co-existed in all but one patient. Management of upper airway obstruction in PRS children is variable between units. Over a 5-year period, 96% of children with PRS were successfully managed without surgical intervention at the Queensland Children's Hospital. These findings contrast with some other literature and may suggest that more careful consideration of surgical intervention in PRS patients is prudent.

Implementation of Mandibular Distraction Osteogenesis for Patients With Pierre Robin Sequence in a Developing Country Through International Collaboration: A Paradigm for Success.

Though it has made significant strides, Vietnam remains a resource-constrained country of 98 million people. Vietnam National Children's Hospital (VNCH) provides tertiary care to a catchment of 40 million people and is the sole national children's hospital. As such, it is one of the few referral centers in the country equipped to take care of patients diagnosed with Pierre Robin sequence (PRS) as this requires pulmonary, critical care, otolaryngology, and plastic surgery expertise. Before 2015, the only surgical options were tongue lip adhesion or tracheostomy. Only 20% of patients successfully avoided tracheostomy, mechanical ventilation, or death. From 2015 to 2019, mandibular distraction osteogenesis (MDO) was introduced by visiting international surgeons on a short-term basis. Since 2020, local surgeons at VNCH have refined their technique and widely use MDO independently. This report seeks to capitulate their experience and identify factors leading to success. A retrospective review was conducted of patients diagnosed with PRS at VNCH from 2015 to 2022. Paper records were digitized, translated, and reviewed for inclusion criteria, including demographics, indications, hospital course, and postoperative outcomes. Complete records satisfying inclusion criteria were available for 53 patients with a diagnosis of PRS who underwent MDO from 2020 to 2022. From 2015 to 2019, there were 19 cases of MDO, though records were incomplete. The median age at the time of MDO was 50 ± 43 days. Forty patients (75.5%) had isolated PRS and 13 (24.5%) were syndromic. Forty-four patients (83%) had a cleft palate. Fifty-one (96.2%) of patients required preoperative supplemental oxygen or mechanical ventilation. The active distraction and consolidation phase was 4.8 ± 1.3 months. The median days to discharge after surgery was 19.0 ± 8.3 days. Median weight at birth, at the time of surgery, and at the time of device removal were 6.8 ± 1.2, 7.7 ± 1.9, and 14.8 ± 2.8 pounds, respectively. Fifty-two patients (98.1%) had obstructive sleep apnea preoperatively with an average Apnea Hypopnea Index of 25.0 ± 10.6. Post-MDO, only 4 (7.5%) had obstructive sleep apnea and the average Apnea Hypopnea Index was 5.2 ± 0.6. No patients (0) required a tracheostomy for a 100% success rate. The tremendous success of the implementation of MDO by local surgeons in Vietnam after its introduction by visiting international surgeons illustrates a paradigm for capacity-enhancing global surgical endeavors. Mandibular distraction osteogenesis has replaced tongue lip adhesion as the surgical treatment of choice for PRS patients at VNCH. Surgical techniques can be transferred to operating environments with basic infrastructure through collaboration and resource optimization. These results demonstrate that global surgical engagement may be scalable and repeatable with direct benefits for patients in lower-middle-income countries.

The Outcome of Mandibular Distraction Osteogenesis in Infants with Severe Pierre Robin Sequence in Vietnam.

The purpose of this study was to provide the experience of a single center with mandibular distraction osteogenesis (MDO) in Pierre Robin Sequence (PRS) patients. A longitudinal research analysis was conducted to identify PRS patients who underwent MDO at Vietnam National Children's Hospital between 2019 and 2021. The following criteria were used to determine inclusion: 1) those pediatric patients with PRS who were not well handled with conservative therapy, 2) those who received MDO with internal mandibular distractors, and 3) no previous treatment elsewhere. Demographic data, postoperative complications, and surgical results were all evaluated. The inclusion criteria were met by 73 patients. There were no difficulties associated with our distraction strategy. The majority of individuals with tracheostomies were successfully decannulated, and the remainder were able to avoid tracheostomies. Using MDO in PRS is an effective technique to avoid future airway issues. The success rate was lower and the complication rate higher for patients who had a tracheotomy before distraction and for those who underwent distraction at an age older than 2 months. The presence of laryngomalacia, gastric reflux disease, cardiac abnormalities, and GI anomalies did not increase the likelihood of MDO failure in PRS patients.

Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus

Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate SOX9 expression at genomic distances over 1.25 Mb. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. We observed pronounced changes in locus topology between cell types. Subsequent analysis of single-chromatin fiber traces revealed that these ensemble-average differences arise through changes in the frequency of commonly sampled topologies. We further identified two CTCF-bound elements, internal to the SOX9 topologically associating domain, which promote stripe formation, are positioned near the domain's 3D geometric center, and bridge enhancer-promoter contacts in a series of chromatin loops. Ablation of these elements results in diminished SOX9 expression and altered domain-wide contacts. Polymer models with uniform loading across the domain and frequent cohesin collisions recapitulate this multi-loop, centrally clustered geometry. Together, we provide mechanistic insights into architectural stripe formation and gene regulation over ultra-long genomic ranges.

Polysomnography-guided mandibular distraction osteogenesis in Pierre Robin sequence patients.

Craniofacial malformations with micrognathia cause high grades of obstructive sleep apnea (OSA) measured by polysomnography (PSG). Mandibular distraction osteogenesis is a novel procedure for upper airway obstruction relief. Our primary objective was to describe the utilization of PSGs to improve obstruction in patients undergoing mandibular distraction. This is a retrospective study. Patients with micrognathia and severe upper airway obstruction, presenting with severe OSA diagnosed by PSG, were included from a single tertiary care center between 2015 and 2019. PSGs were done (1) prior to surgery, (2) once the cosmetic goal was achieved (Post-Op 1), and (3) if residual moderate-to-severe OSA was seen, every 2 nights until mild or no OSA was achieved (Post-Op 2). Thirteen patients were included. The median age at surgery was 1.1 months (10 days-3 months). All 13 patients had baseline severe OSA, with a median obstructive apnea-hypopnea index of 33 events/h and a median O2 nadir of 73%. Post-Op 1 PSG was done at a median of 6 days after surgery. Median first postoperative obstructive apnea-hypopnea index in all 13 patients was 6.8 events/h, with a median O2 nadir of 87%. A median additional distraction of 3 mm was needed beyond the traditionally recommended advancement. Long-term follow-up studies at or after 1 year were done in 5 patients, all showing persistent nonsevere OSA. This is the first case series utilizing PSGs as a guide for mandibular distraction osteogenesis in patients with micrognathia showing the need for jaw overcorrection to achieve resolution of OSA. Kochhar R, Modi V, de Silva N, etal. Polysomnography-guided mandibular distraction osteogenesis in Pierre Robin sequence patients. J Clin Sleep Med. 2022;18(7):1749-1755.

Next Generation Sequencing and Cytogenetic Based Evaluation of Indian Pierre Robin Sequence Families Reveals CNV Regions of Modest Effect and a Novel LOXL3 Mutation.

Pierre Robin Sequence (PRS) affects approximately 1 per 8500 to 14000 new-borns worldwide. Although the clinical entity is well defined, the pathogenesis of PRS is debated. The present study aims to understand the contribution of genomic imbalances and genetic variants in patients clinically diagnosed of PRS. A total of 7 independent patients with nonsyndromic PRS thoroughly evaluated by a medical geneticist at a tertiary care hospital, were included in the study. Blood samples were collected from these patients and their family members. Array CGH was performed on all 7 patients and their respective family members for detection of underlying cytogenetic defects. Whole exome sequencing (WES) was performed for 5 families to capture single nucleotide variants or small indels. Cytogenetic analyses did not detect any previously reported gross chromosomal aberrations for PRS in the patient cohort. However, copy number variations (CNVs) of size <1 Mb were detected in patients which may have implications in PRS. The present study provided evidence for the occurrence of de novo deletions at 7p14.1 locus in PRS patients: further validating the candidate loci susceptibility in oral clefts. WES data identified LOXL3 as candidate gene, carrying novel deleterious variant, which is suggestive of the role of point mutations in the pathogenesis of PRS. The present study offered considerable insight into the contribution of cytogenetic defects and novel point mutation in the etiology of nonsyndromic PRS. Studies comprising large number of cases are required to fully elucidate the genetic mechanisms underlying the PRS phenotype.

Study on the Effect of Bilateral Mandible Distraction Osteogenesis About the Nutrition Status of Infants With Pierre-Robin Sequence.

Objective: By comparing and studying the changes of food intake, weight, body length, BMI, blood albumin level and other indicators of infants with Pierre-Robin Sequence (PRS) before and after Bilateral Mandible Distraction Osteogenesis operation, to explore the effect of distraction osteogenesis on PRS patients about the improvement of nutrition status.Methods: The children with PRS who admitted to the Oral and Maxillofacial Surgery Department of Guangzhou Women and Children's Medical Center from July 2015 to December 2020 were selected. All patients accepted bilateral mandible distraction osteogenesis surgery, and the pre- and post-operative indicators were recorded, such as food intake, weight, length, blood albumin level and others. BMI was calculated based on the indicators mentioned above, and comparative statistical analysis was performed.Results: 1. All patients were fed with whole milk before the first surgery, and the average calorie per kg was 91.8 kcal/kg, significantly lower than the standard (100–150 kcal/kg), suggesting the overall nutritional intake of PRS patients is low; 2. t tests for independent samples were used to analyze the pre-operative and post-operative indicators. The WFA percentile increased from 14.16 ± 2.17 to 15.01 ± 1.85% (P = 0.0048), WFA z score increased from −2.40 ± 0.18 to −1.90 ± 0.14 after the surgery (P = 0.0010), LFA percentile increased from 20.04 ± 3.48 to 33.67 ± 4.29% (P = 0.0098), LFA z score increased from −2.09 ± 0.19 to −1.42 ± 0.23 (P = 0.0009), BMI z score increased from −1.95 ± 0.22 to −1.39 ± 0.16 (P = 0.0408), ALB raised from 37.06 ± 0.51 to 42.85 ± 0.30 g/L (P < 0.001), which indicating that the physique of patients improved after the distraction osteogenesis surgery, mainly was reflected by the lifting of weight and length growth curves; the body shape also improved, indicating that the patients' nutrition status after the surgery is also improved.Conclusion: Bilateral mandible distraction osteogenesis surgery has a positive effect on the nutrition status of children with PRS. This effect is mainly reflected by the improvements of the body physical indicators after surgery.

1173 Airway and Breathing Problems in Pierre Robin Sequence: A Systematic Review Protocol

Abstract Aim The primary aim is to systematically review the specific airway and/or breathing problems which have been reported in Pierre Robin Sequence (PRS). Secondary aims are to understand the prevalence and severity of these airway and breathing problems, and options for screening, assessment, and monitoring. Method A search strategy will be designed to search the following databases: MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials(CENTRAL) including a grey literature search, to identify publications on airway and/or breathing problems in Pierre Robin Sequence patients. Airway or breathing problems to be included are defined upper airway conditions (e.g., sleep apnoea) or clinically or objectively defined airway/breathing problems (e.g., increased respiratory rate, polysomnography). Screening will exclude non-English articles, abstracts, letters, editorials, expert opinions and breathing problems not anatomically related to craniofacial underdevelopment. Results This systematic review has been successfully registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42020210572) Conclusions PRS is a rare craniofacial condition which presents at birth, consisting of micrognathia, glossoptosis and airway problems, and is usually, but not always, associated with a cleft palate. There is no consensus on the type of airway problems that affect patients with PRS. The findings of this systematic review will help to develop a consensus on the airway and breathing problems in PRS and options for assessment and monitoring of the airway and breathing problem. This data may also contribute to development of a standardized guideline for management of airway and breathing problems in PRS.

Maxillomandibular Development after Mandibular Distraction Osteogenesis in Isolated Pierre Robin Sequence Patients

Mandibular distraction osteogenesis (MDO) is a favored surgical technique for addressing the airway difficulties that result in patients with Pierre Robin sequence. Devices are placed to distract the micrognathic mandible forward and generate bone at bilateral mandibular osteotomies.1 Though it is generally accepted that these patients will continue to develop with disproportionate maxillomandibular growth after distraction2, the timeline for relapse back to a skeletal class II relationship, as well as differences between male and female development post-distraction, is not well-described.The purpose of this study is to characterize a timeline of maxillomandibular growth for patients with isolated Pierre Robin sequence (iPRS) after MDO during infancy based on Steiner's analysis and clinical impressions, as well as to identify differences in post-distraction growth between males and females. The researchers hypothesized that these patients would demonstrate disproportionate growth after distraction and that females would relapse at a faster rate than males. By improved understanding of this timeline, clinicians may better educate parents with expectations for their child's craniofacial development after distraction.Department records were retrospectively reviewed to identify patients with iPRS who underwent MDO during infancy from 2004 through 2016. Patients with post-distraction imaging from which cephalometric data could be traced (i.e., lateral cephalograms or cone beam computerized tomography [CBCT] scans) were included. These were traced by 2 independent reviewers for SNA, SNB, and ANB angles, according to Steiner's analysis to determine skeletal classification. Patients with pre- and post-distraction lateral profile photos were assessed by 1 reviewer for skeletal classification based on clinical appearance. Patient age at distraction, sex, time from initial distraction to imaging study, and prior maxillomandibular surgeries were abstracted. Descriptive statistics and significance testing were performed; 38 patients with iPRS who underwent MDO were identified. Of these, 15 (39.5%) had at least 1 postoperative lateral cephalogram. Average time from surgery to initial lateral cephalogram (TAS) was 67.81 months for all patients (range 25.53 to 129.93 months). The majority of patients (n = 12) had an ANB > 2° at the time of lateral cephalogram. One patient (TAS 25.53 months) had an ANB of 1.3°, whereas 2 patients (both with prior cleft palate repair) had an ANB < 0° (TAS 32.67 and 97.17 months). Nine (60%) of all patients with lateral cephalogram data fell within 1 standard deviation of average TAS (39.52 to 96.1 months), with corresponding average SNA, SNB, and ANB angles of 80.97, 73.99, and 7.03, respectively; 33% of these patients (n = 3) had prior palatal surgery. Of the 38 patients, 37 had pre- and post-distraction lateral photographs; 13 of 15 (86.7%) females, and 12 of 22 (54.5%) males relapsed to a skeletal class II relationship by the last follow-up appointment (P = .04). The mean postoperative follow-up months for females (69.3 months) and males (79.9 months) was similar (P = .50). Based on post-distraction cephalometric tracing, 80% of patients reverted back to a skeletal class II relationship by an average of 68 months. Based on post-distraction clinical appearance, 68% of patients reverted to a class II relationship by an average of 76 months. Furthermore, a more significant percentage of females relapsed to a skeletal class II relationship compared to males at similar follow-up points. These findings may help clinicians and parents better understand and prepare for the maxillomandibular developmental timeline of these patients post-distraction.

Maxillomandibular Development after Mandibular Distraction Osteogenesis in Isolated Pierre Robin Sequence Patients

Mandibular distraction osteogenesis (MDO) is a favored surgical technique for addressing the airway difficulties that result in patients with Pierre Robin sequence. Devices are placed to distract the micrognathic mandible forward and generate bone at bilateral mandibular osteotomies.1 Though it is generally accepted that these patients will continue to develop with disproportionate maxillomandibular growth after distraction2, the timeline for relapse back to a skeletal class II relationship, as well as differences between male and female development post-distraction, is not well-described.The purpose of this study is to characterize a timeline of maxillomandibular growth for patients with isolated Pierre Robin sequence (iPRS) after MDO during infancy based on Steiner's analysis and clinical impressions, as well as to identify differences in post-distraction growth between males and females. The researchers hypothesized that these patients would demonstrate disproportionate growth after distraction and that females would relapse at a faster rate than males. By improved understanding of this timeline, clinicians may better educate parents with expectations for their child's craniofacial development after distraction.Department records were retrospectively reviewed to identify patients with iPRS who underwent MDO during infancy from 2004 through 2016. Patients with post-distraction imaging from which cephalometric data could be traced (i.e., lateral cephalograms or cone beam computerized tomography [CBCT] scans) were included. These were traced by 2 independent reviewers for SNA, SNB, and ANB angles, according to Steiner's analysis to determine skeletal classification. Patients with pre- and post-distraction lateral profile photos were assessed by 1 reviewer for skeletal classification based on clinical appearance. Patient age at distraction, sex, time from initial distraction to imaging study, and prior maxillomandibular surgeries were abstracted. Descriptive statistics and significance testing were performed; 38 patients with iPRS who underwent MDO were identified. Of these, 15 (39.5%) had at least 1 postoperative lateral cephalogram. Average time from surgery to initial lateral cephalogram (TAS) was 67.81 months for all patients (range 25.53 to 129.93 months). The majority of patients (n = 12) had an ANB > 2° at the time of lateral cephalogram. One patient (TAS 25.53 months) had an ANB of 1.3°, whereas 2 patients (both with prior cleft palate repair) had an ANB < 0° (TAS 32.67 and 97.17 months). Nine (60%) of all patients with lateral cephalogram data fell within 1 standard deviation of average TAS (39.52 to 96.1 months), with corresponding average SNA, SNB, and ANB angles of 80.97, 73.99, and 7.03, respectively; 33% of these patients (n = 3) had prior palatal surgery. Of the 38 patients, 37 had pre- and post-distraction lateral photographs; 13 of 15 (86.7%) females, and 12 of 22 (54.5%) males relapsed to a skeletal class II relationship by the last follow-up appointment (P = .04). The mean postoperative follow-up months for females (69.3 months) and males (79.9 months) was similar (P = .50). Based on post-distraction cephalometric tracing, 80% of patients reverted back to a skeletal class II relationship by an average of 68 months. Based on post-distraction clinical appearance, 68% of patients reverted to a class II relationship by an average of 76 months. Furthermore, a more significant percentage of females relapsed to a skeletal class II relationship compared to males at similar follow-up points. These findings may help clinicians and parents better understand and prepare for the maxillomandibular developmental timeline of these patients post-distraction.

Characterization of phenotypes and predominant skeletodental patterns in pre-adolescent patients with Pierre-Robin sequence.

ObjectiveTo investigate the phenotypes and predominant skeletodental pattern in pre-adolescent patients with Pierre–Robin sequence (PRS).MethodsThe samples consisted of 26 Korean pre-adolescent PRS patients (11 boys and 15 girls; mean age at the investigation, 9.20 years) treated at the Department of Orthodontics, Seoul National University Dental Hospital between 1998 and 2019. Dental phenotypes, oral manifestation, cephalometric variables, and associated anomalies were investigated and statistically analyzed.ResultsCongenitally missing teeth (CMT) were found in 34.6% of the patients (n = 9/26, 20 teeth, 2.22 teeth per patient) with 55.5% (n = 5/9) exhibiting bilaterally symmetric missing pattern. The mandibular incisors were the most common CMT (n = 11/20). Predominant skeletodental patterns included Class II relationship (57.7%), posteriorly positioned maxilla (76.9%) and mandible (92.3%), hyper-divergent pattern (92.3%), high gonial angle (65.4%), small mandibular body length to anterior cranial base ratio (65.4%), linguoversion of the maxillary incisors (76.9%), and linguoversion of the mandibular incisors (80.8%). Incomplete cleft palate (CP) of hard palate with complete CP of soft palate (61.5%) was the most frequently observed, followed by complete CP of hard and soft palate (19.2%) and CP of soft palate (19.2%) (p < 0.05). However, CP severity did not show a significant correlation with any cephalometric variables except incisor mandibular plane angle (p < 0.05). Five craniofacial and 15 extra-craniofacial anomalies were observed (53.8% patients); this implicated the need of routine screening.ConclusionsThe results might provide primary data for individualized diagnosis and treatment planning for pre-adolescent PRS patients despite a single institution-based data.

Impact of Cleft Palate on Tongue-Based Upper Airway Obstruction in Pierre Robin Sequence: Implications for Mandibular Distraction Osteogenesis and Timing of Cleft Palate Repair

The objectives of this study are to analyze the impact of cleft palate (CP) on upper airway obstruction using polysomnography in patients with Pierre Robin Sequence (PRS) undergoing mandibular distraction osteogenesis (MDO) and subsequent CP repair. A single-surgeon, retrospective chart review was performed of all patients with nonsyndromic PRS treated with MDO. Severity of upper airway obstruction was evaluated pre- and post-distraction via polysomnography. Details of MDO and CP repair were collected and any complications recorded. Twenty-one nonsyndromic PRS patients with CP and 6 patients without CP met inclusion criteria. There was no significant difference in predistraction apnea-hypopnea index between the 2 groups (53.4 ± 42.1 versus 34.4 ± 18.9; P = 0.3). Patients with CP had significantly higher predistraction SpO2 saturation (94.5 ± 1.6% versus 91.0% ± 4.8%; P = 0.01), SpO2 nadir (74.5% ± 9.1% versus 63.6% ± 11.6%; P = 0.03) and lower percentage time spent below 90% SpO2 (6.0% ± 7.2% versus 23.6% ± 29.9%; P = 0.04). The rate of oronasal fistulas formation was 38%. The time between MDO and CP repair was shorter for patients with complications (250.8 ± 3.3 versus 370.8 ± 191.9 days; P = 0.08). Five patients experienced relapse of respiratory difficulties after CP repair. The presence of CP in nonsyndromic PRS patients decreases the severity of obstructive sleep apnea by oxygen parameters on PSG. Palatal fistulas and relapse of respiratory distress are common complications of CP repair following MDO. Delaying CP repair may help to decrease complication rates.

Mandibular Distraction Osteogenesis as a Primary Intervention in Infants With Pierre Robin Sequence.

Pierre Robin sequence (PRS) is a triad of congenital facial abnormalities that can present as a syndrome (syndromic PRS [sPRS]) or an isolated entity (isolated PRS [iPRS]). Patients with PRS can develop airway and feeding problems that may result in failure to thrive. Mandibular distraction osteogenesis (MDO) is a method for improving the functional issues associated with breathing and feeding. There is a Paucity of literature evaluating the outcomes of MDO between sPRS and iPRS patients. An institutional review board-approved retrospective review of PRS patients managed by a single surgeon and treated with MDO between January 2015 and December 2019 at a tertiary referral hospital was performed. The patients were stratified into iPRS or sPRS based on gene testing. Airway outcome measures included avoidance of tracheostomy, relief of sleep apnea, and oxygen saturation improvement. Primary feeding measures included achievement of full oral feeds and growth/weight gain. Statistical analysis included t tests and χ2 tests where appropriate using SPSS. Over the study period, of the 29 infants with PRS, 55% identified as iPRS and 45% as sPRS. There were no significant differences in the patient characteristics, apnea-hypoxia index (22.27 ± 12.27) and laryngeal view (3 ± 0.79) pre-MDO. After MDO, 83% of the subjects achieved a positive feeding outcome and 86% achieved a positive airway outcome with no statistical significance between sPRS and iPRS (P = 0.4369). There was a statistically significant change post-MDO in apnea-hypoxia index (5.24 ± 4.50, P = 0.02) and laryngeal view (1.59 ± 1.00, P = 0.01). Our recent experience would lead us to believe that sPRS patients have greater morbidities and challenging clinical developments that, when properly evaluated, can be managed by MDO. There is a potential role for MDO in reducing the need for traditional surgical interventions for respiratory and feeding problems in both iPRS and sPRS patients.

Respiratory sleep disorders, nasal obstruction and enuresis in children with non-syndromic Pierre Robin sequence

IntroductionObstructive sleep apnea is highly prevalent in non-syndromic Pierre Robin sequence patients. Studies have found a probable relationship between obstructive sleep apnea and nasal obstruction and between obstructive sleep apnea and enuresis. Assessment of the relationship between these variables in non-syndromic Pierre Robin sequence patients is scarce. ObjectiveThe present study aims to evaluate the relationship between symptoms of obstructive sleep apnea, nasal obstruction and enuresis, determining the prevalence of symptoms suggestive of these conditions, in schoolchildren with non-syndromic Pierre Robin sequence, and describe the prevalence of excessive daytime sleepiness habitual snoring and voiding dysfunction symptoms associated with enuresis. MethodsThis was a prospective analytical cross-sectional study developed at a reference center. Anthropometric measurements and a structured clinical interview were carried out in a sample of 48 patients. The instruments “sleep disorders scale in children” “nasal congestion index questionnaire” (CQ-5), and the “voiding dysfunction symptom score questionnaire” were used. Statistical analysis was performed for p < 0.05. ResultsPositive “sleep disorders scale in children” scores for obstructive sleep apnea and CQ-5 for nasal obstruction were observed in 38.78% and 16.33%, respectively. Enuresis was reported in 16.33% of children, being characterized as primary in 71.43% and polysymptomatic in 55.55%; according to the “voiding dysfunction symptom score questionnaire”. There was a significant relationship between nasal obstruction and obstructive sleep apnea symptoms (p < 0.05), but no significance was found between obstructive sleep apnea symptoms and enuresis, and between nasal obstruction and enuresis. The prevalence of excessive daytime sleepiness was 12.24% and of habitual snoring, 48.98%. A family history of enuresis, younger age in years and a positive “voiding dysfunction symptom score questionnaire” score were associated with a higher prevalence of enuresis (p < 0.05). ConclusionChildren with non-syndromic Pierre Robin sequence are at high risk for obstructive sleep apnea symptoms and habitual snoring, with a correlation being observed between nasal obstruction and obstructive sleep apnea symptoms. In addition, the study showed that non-syndromic Pierre Robin sequence, obstructive sleep apnea and nasal obstruction symptoms were not risk factors for enuresis in these patients.

Palatal Re-Repair With Z-Plasty in Treatment of Velopharyngeal Insufficiency of Syndromic and Nonsyndromic Patients With Cleft Palate.

Velopharyngeal insufficiency (VPI) often results from palatal shortening or insufficient levator function after cleft palate repair. To assess the efficacy of palatal re-repair with Z-plasty in treatment of VPI for patients with isolated cleft palate (ICP). This retrospective analysis comprised 130 consecutive patients who had ICP with VPI that required Z-plasty as secondary surgery between 2008 and 2017. Pre- and post-operative evaluation of velopharyngeal function was done perceptually and instrumentally by Nasometer. Median patient age at Z-plasty was 6.8 years (range 3.0-20.1). Of the 130 patients, preoperatively VPI was severe in 73 (56%), mild-to-moderate in 55 (42%), and borderline in 2 (2%). Postoperatively, 105 (81%) of patients achieved adequate (normal or borderline) velopharyngeal competence and 16 (12%) required second operation for residual VPI. The success rate was 84% in nonsyndromic patients, 79% in nonsyndromic Pierre Robin sequence patients, and 58% in syndromic patients. In syndromic children, the speech outcome was significantly worse than in nonsyndromic children (P = 0.014). Complications included wound healing problems in 3 patients (2%), mild infection in 1 patient (1%), postoperative bleeding in 1 (1%), and postoperative fistula in 2 (2%). Palatal re-repair with Z-plasty is a safe operation for VPI correction in patients with ICP with a success rate of 81%. In syndromic patients, the procedure did not seem to work as well as in nonsyndromic patients.

Long-Term Orthognathic Considerations in the Pierre Robin Sequence Patient.

One of the arguments against early intervention for micrognathia in Pierre Robin sequence is the concept that the growth of the mandible will eventually "catch up." Long-term growth of the mandible and occlusal relationships of conservatively managed Pierre Robin sequence patients remain unknown. In this study, the authors evaluated the orthognathic surgery requirements for Pierre Robin sequence patients at skeletal maturity. Orthognathic surgical requirements of conservatively managed Pierre Robin sequence and isolated cleft patients (aged ≥13 years) at two institutions were reviewed and analyzed using t test, chi-square test, and Fisher's exact test. Values of p < 0.05 were considered statistically significant. Of the Pierre Robin sequence patients (n = 64; mean age ± SD, 17.9 ± 2.9 years), 65.6 percent were syndromic (primarily Stickler and velocardiofacial syndrome), 96.9 percent had a cleft palate, and 39.1 percent required orthognathic surgery at skeletal maturity. Nonsyndromic and syndromic Pierre Robin sequence patients demonstrated no differences in occlusal relationships or mandibular surgery frequency. The majority of Pierre Robin sequence patients requiring mandibular advancement had a class II occlusion. Comparison of Pierre Robin sequence patients to isolated cleft palate patients (n = 17) revealed a comparable frequency of orthognathic surgery between the two; however, Pierre Robin sequence patients did require mandibular advancement surgery at a greater frequency than cleft palate patients (p = 0.006). The present study found that 39.1 percent of conservatively managed Pierre Robin sequence patients required orthognathic surgery at skeletal maturity, of which the vast majority required mandibular advancement for class II malocclusion. These data suggest that mandibular micrognathia in conservatively managed Pierre Robin sequence patients may not resolve over time and may require surgical intervention. Risk, II.

Quantification of Mandibular Morphology in Pierre Robin Sequence to Optimize Mandibular Distraction Osteogenesis.

Mandibular distraction osteogenesis (MDO) is the primary surgical intervention to treat airway obstruction in Pierre Robin sequence (PRS). Current morphologic studies of PRS mandibles do not translate into providing airway management decisions. We compare mandibles of infants with nonsyndromic PRS to controls characterizing morphological variances relevant to distraction. We also examine how morphologic measurements and airway grades correlate with airway management. Patients with PRS under 2 months old were age and sex matched to controls. Demographic and perioperative data, and Cormack-Lehane airway grades were recorded. Computed tomography scans were used to generate mandibular models. Bilateral condylions, gonions, and the menton were identified. Linear and angular measurements were made. Wilcoxon rank sum and 2-sample t tests were performed. Twenty-four patients with PRS and 24 controls were included. Seventeen patients with PRS required MDO. PRS patients had shorter ramus heights (16.7 vs 17.3 mm; P = .346) and mandibular body lengths (35.3 vs 39.3 mm; P < .001), more acute gonial angles (125.3° vs 131.3°; P < .001), and more obtuse intergonial angles (94.2° vs 80.4°; P < .001) compared to controls. No significant differences were found among patients requiring MDO versus conservative management nor among distracted patients with high versus low airway grades. Our study examines the largest and youngest PRS population to date regarding management of early airway obstruction with MDO. Our findings indicate that univector mandibular body distraction allows for normalization in nonsyndromic patients with PRS, and airway obstruction management decisions should remain clinical.

Abstract 147: Mandibular Measurements At The 20-Week Anatomy Ultrasound As A Prenatal Predictor Of The Severity Of Pierre-Robin Sequence Associated Respiratory Distress

Purpose: Pierre-Robin Sequence (PRS) is defined as micrognathia and glossoptosis leading to upper airway obstruction and possible respiratory distress. Prenatal diagnosis of PRS is key in preparing the delivery team for an airway emergency. Routine 20-week ultrasounds do not screen facial features, which would allow for the evaluation of maxilla-mandibular relationships and mandible size. This study aimed to evaluate 20-week ultrasounds of infants diagnosed with PRS to determine if specific facial measurements could predict PRS disease severity. Methods: A retrospective review of patients with PRS born between December 2014 and March 2019 was performed. NICU and surgical data were collected. Respiratory and surgical interventions were recorded and scored for severity. Mid-sagittal profile images of the anatomy ultrasound were reviewed for each patient, and 3 parameters were measured to assess for micrognathia: facial-maxillary angle (FMA), facial nasomental angle (FNMA), and alveolar overjet. Results: 70 PRS patients were reviewed. 40 were excluded for unavailable ultrasounds. Of the remaining 30, 43% had an FMA below 66°, suggesting micrognathia (range: 47-82°, mean: 65.17°). For FNMA, 77% were below 136°, suggesting micrognathia (r: 104-154°, m: 130.9°). Mean alveolar overjet was 3.6mm (r: 2-7mm). Respiratory outcomes: 12 of 30 patients required no external respiratory support (40%), 11 needed supplemental oxygen by nasal cannula or CPAP (36.7%) and 7 were intubated (23.3%). As respiratory support severity increased, median FMA decreased and alveolar overjet increased, though these differences were not statistically significant. For patients with respiratory independence, median FMA was 68.5° (59.5, 74.75) while the CPAP/NC group had a median FMA of 66° (57, 66) and the intubated group had a median FMA of 65° (52, 66). Alveolar overjet for patients with no respiratory support revealed a median 3.1mm overjet, CPAP/NC patients had 3.2mm, and intubated patients had 3.8mm. Surgical intervention: 11 patients had no surgical procedures (36.5%), 5 patients underwent supraglottoplasty (16.7%), 13 received mandibular distraction or tongue-lip adhesion (14.3%), and 1 required a tracheostomy (3.3%). There was no statistically significant difference in mean ultrasound measurements between surgical and nonsurgical patients. However, surgical patients tended to have smaller FNMAs and greater overjet compared to nonsurgical patients; median FNMA was 131° versus 132°, and median overjet was 3.2 versus 3.1 mm, respectively. Five patients required no respiratory or surgical intervention. Conclusions: In a population of patients with PRS, prenatal facial features on the 20-week ultrasound can be measured. While most patients with PRS at this gestational age had a normal FMA, the majority of patients had an abnormally acute FNMA. Alveolar overjet, previously not described in prenatal ultrasound literature but routinely assessed on neonatal clinical evaluation, is measurable and may have utility in prenatal diagnosis.

Weight gain in infants with Pierre Robin sequence

ObjectiveTo determine weight gain during treatment with the modified palatal plate (MPP) in infants with isolated and syndromic Pierre Robin Sequence (PRS) suffering from micrognathia, upper airway obstruction (UAO), and failure to thrive (FTT), the authors conducted a retrospective study of infants treated with the MPP. MethodsThe main outcome measure was infant weight (g) for up to three months after birth. Demographic and outcome data (associated syndromes, comorbidities, presence of cleft lip or palate, intubation attempts, tracheotomy and cleft repair) were collected. Results14 children born January 2010 - December 2019 were included. The majority (86%) of infants showed highly significant weight gain (p < 0.001) within a 3-month period (mean pretreatment weight 3147 g with a SD of 425 g vs mean weight at three months 4435 g with a SD of 635 g). Syndromic PRS was found in 7% of infants. 43% of nonsyndromic PRS patients were found to have other congenital anomalies. Genetic testing showed normal karyotypes in 93% of infants and a microdeletion in 7% of infants. 21% of infants required tracheotomy, but no patients required mandibular distraction (MDO) or tongue-lip adhesion (TLA) to relieve UAO. ConclusionPRS infants treated with the MPP showed highly significant weight gain within a 3-month period and did not require mandibular surgery for early airway management, but faster gain of weight might have implications for strategies to perform surgery at an earlier point in time.