Evaluating 3D Morphometrics for Assessing Micrognathia in Neonates with Severe Pierre Robin Sequence: A Case-Control Study.

We present a case of Pierre Robin sequence and Neonatal Abstinence Syndrome (NAS) in a newborn female patient to highlight the surgical technique of mandibular distraction osteogenesis to correct airway obstruction due to micrognathia. The patient presented as a transport after delivery due to respiratory distress. She was noted to have a cleft palate and micrognathia. The absence of other dysmorphic features diagnosed her with non-syndromic Pierre Robin sequence. To solve her upper airway obstruction, mandibular distraction osteogenesis was performed. This procedure allowed the patient to be weaned from all respiratory support and nasogastric tube feeds by the end of her hospitalization. She was able to be discharged home weeks before her internal hardware was surgically removed. Mandibular distraction osteogenesis was previously unavailable in rural Appalachia, making this case novel to the area. The patient also developed NAS during her hospitalization, highlighting the ongoing substance abuse epidemic in Appalachia.

Pierre Robin sequence (PRS) is characterized by micrognathia, glossoptosis, and upper airway obstruction. This study aimed to compare the dentoskeletal characteristics of children diagnosed with non-syndromic PRS and those with cleft palate. This study was conducted on the non-syndromic PRS patients in the database of our hospital. The control group of non-syndromic isolated incomplete cleft palate patients was matched from the same database by age, gender and weight in a 1:3 ratio. The dentoskeletal characteristics were compared between the PRS and control groups. The study included 14 patients in the PRS group and 42 patients in the control group. A point-Nasion-B point (ANB) angle was significantly greater in the PRS group compared with the control group. The PRS group exhibited a significantly lower ratio of the linear distance between Articulare and Gonion (ArGo) to the distance between Gonion and Pogonion (GoPo) compared to the control group. Additionally, the anteroposterior length and area of the lower pharyngeal airway space (LPAS) were markedly reduced in the PRS group. The ANB angle, the ArGo/GoPO ratio and the anteroposterior length and area of LPAS could serve as valuable indicators to identify micrognathia in patients with non-syndromic PRS.

Introduction: Pierre Robin Sequence (PRS) is characterized by the presence of micrognathia, glossoptosis, and airway obstruction. While syndromic children may require multiple procedures to address airway obstruction and malocclusion, one of the controversies in non-syndromic PRS is the potential for “catch-up” mandibular growth equivalent to children without craniofacial diagnoses. Here, we evaluate long-term requirements of orthognathic surgery at skeletal maturity in PRS patients. Methods: 115 children diagnosed with PRS were evaluated from institutions. Children ≥13 years of age were included and patients who underwent any type of mandibular distraction or surgery prior to skeletal maturity were excluded. Demographics, surgical, and orthodontic histories were reviewed. Descriptive statistics were reported. Chi-square was used to compare groups. Results: 43 patients with PRS met inclusion criteria (57% female; mean age: 20 ± 3.3 years). Mean length of follow up was 14.2 ± 5.2 years. 18 patients (41%) were diagnosed as syndromic, the majority of which was Stickler Syndrome. 41 patients (95%) had a history of a cleft palate and of those patients, 18 (44%) had velopharyngeal insufficiency necessitating surgery. Data was available for 42 patients in regards to orthodontic and orthognathic care. Orthodontic evaluation revealed that 41 patients (98%) had a history of orthodontic treatment and 20 (48%), 17 (40%), and 5 (12%) were classified as Angle Class I, II, and III, respectively. Subset analysis revealed that 13 and 4 patients with a syndromic diagnosis were Class I and class II, respectively, while 1 was class III (p<0.05). A total of 17 (39.5%) patients underwent or were recommended to undergo orthognathic surgery due to Class II (n=11/17, 65%) or Class III (n=3/17, 18%) malocclusion. When PRS children with surgical Class II malocclusion were separated into nonsyndromic versus syndromic subgroups, 9/11 (80%) were nonsyndromic and 2/11 (18%) were syndromic. Overall, 9/25 (36%) of nonsyndromic and 2/18 (11%) of syndromic PRS children required orthognathic surgery to specifically address maxillomandibular and occlusal abnormalities (p=0.09). Conclusion: The presented study suggests deficient long-term mandibular growth of nonsyndromic PRS children is relatively similar to that of children with syndromic PRS. These findings lie in contrast to the concept of mandibular “catch-up” growth and suggest that the maxillomandibular relationship in PRS may not resolve without intervention.

Pierre Robin sequence (PRS) is a triad of micrognathia, glossoptosis, and respiratory distress. There is no standard clinical classification used in the management of neonatal airway in patients with PRS. The goal of our study was to review the presentation and management of patients with PRS and formulate a clinical grading system and treatment algorithm. A 10-year retrospective review of all neonates diagnosed with PRS was performed after obtaining institutional ethics approval. Patients were identified using our cleft lip and palate program database. Inclusion criteria were 2 of the following 3 clinical features-glossoptosis, retrognathia, or airway obstruction. We collected demographic data, clinical information (coexisting airway morbidity, maxillary-mandibular discrepancy, type of intervention used, complications, and outcomes (feeding, length of stay, and airway status) during the first year of life. Sixty-three patients met our inclusion criteria. Of these, 55 (87%) had cleft palate and 17 (27%) were syndromic. Forty-eight (76%) patients were managed by prone positioning. Of the 15 surgically managed patients, the initial procedure was floor of mouth release in 7, mandibular distraction osteogenesis (MDO) in 4, and tongue-lip adhesion in 4. Five patients with coexisting airway morbidity needed a second surgery; 2 had MDO and 3 tracheostomies (one patient was later decannulated). Seven (47%) of the surgically managed patients required a gastrostomy tube. At present, there is no consensus on neonatal airway management in infants with PRS. From our review of 63 patients with PRS, we hereby propose a simple 4-point classification system and treatment algorithm, based on clinical features.

Speech prognosis and need of pharyngeal flap for non syndromic vs syndromic Pierre Robin Sequence

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

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.

To examine the long-term outcomes and complications in infants with upper airway obstruction and feeding difficulty who underwent bilateral mandibular distraction osteogenesis (MDO) within the first 3 months of life and to identify any preoperative characteristics that may predict the long-term outcome following early MDO intervention for airway obstruction. An institutional, retrospective medical chart review was performed. Inclusion criteria were bilateral MDO performed at an age younger than 3 months, with a minimum follow-up of 3 years. A quantitative outcome measures scale was developed, and patients were scored based on long-term postoperative complications as well as airway and feeding goals. Factors such as need for an additional surgical procedure were also considered. Nineteen children were identified as having undergone MDO before 3 months of age and having more than 3 years of follow-up data. The mean age at distraction was 4.8 weeks (range, 5 days-12 weeks); the mean length of follow-up was 5.6 years (range, 37-122 months). Of these 19 patients, 14 had isolated Pierre Robin sequence (PRS) and 5 had syndromic PRS. All patients with isolated PRS had a good or intermediate long-term result. Infants with comorbidities such as developmental delay, seizures, or arthrogryposis had the poorest outcomes. Bilateral MDO is a relatively safe and effective means of treating airway obstruction and feeding difficulty in infants with PRS. The effects of this procedure, which carries a relatively low morbidity, persist through early childhood in most patients.

Prognosis of airway obstruction and feeding difficulty in the Robin sequence

Background: The Pierre Robin sequence (PRS), consisting of cleft palate, micrognathia and glossoptosis, can be seen as part of the phenotype in other Mendelian syndromes—for instance, campomelic dysplasia (CD) which...

The aim of this study was to compare the dentoskeletal pattern of Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS). Retrospective. Single center. Eighteen patients diagnosed with TCS (Group TCS) or PRS (Group PRS) in rehabilitation treatment at a single center. Group TCS was composed of 9 patients (4 male, 5 female) with a mean age of 12.9 years (standard deviation = 4.8). Group PRS was composed of 9 patients paired by age and sex with group TCS. Cone beam computed tomography-derived cephalometric images taken before the orthodontic or the orthodontic-surgical treatment were analyzed using Dolphin Imaging (Dolphin Imaging 11.0 & Management Solutions). Variables evaluating the cranial base, the maxillary and mandibular skeletal components, maxillomandibular relationship, the vertical components and the dentoalveolar region were measured. Intergroup comparisons were performed using t tests. The significance level considered was 5%. Intergroup differences in the mandible size and growth pattern were observed. Group TCS showed a smaller mandibular length (Co-Go, Co-Gn) and a higher palatal plane (SN-Palatal Plane) and mandibular plane angles (SN-Go.Gn) compared to group PRS. No differences between TCS and PRS were observed for the sagittal position of the maxilla, maxillomandibular relationship, and dental components. Treacher Collins syndrome presented a decreased mandible and a more severe vertical growth pattern compared to PRS.

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

Background:The literature does not offer any review of the pathogenesis of the clinical features of syndromes with Pierre Robin sequence (PRS). The senior author (MMA) proposed a hypothesis that SOX9 and its interactions may play a key role in this pathogenesis. The current review aims to test this hypothesis.Methods:Three literature searches were made: the first aimed to document the main syndromes associated with PRS; and the second was to document the main functions of SOX9 in development; and the third was to investigate if SOX9 and its interactions may play a role in the pathogenesis.Results:SOX9 is the main positive regulator in the development of the mandibular cartilage and it also enhances collagen type II (the main collagen type in cartilage) expression in the mandibular cartilage. Furthermore, SOX9 participates in neural crest development, binds to the exon junction complex, and participates in sex determination. The interactions of SOX9 could explain the pathogenesis of the clinical features of syndromic PRS. These included interactions with collagen type II (in Strickler syndrome), exon junction complex (in Richier-Costa–Periera syndrome), glucose (in Catel–Manzke syndrome), RNA-binding proteins (in TARP syndrome), and the spliceosome (in cerebra-costo-mandibular syndrome). Finally, SOX9 mutations cause campomelic dysplasia.Conclusions:The review supports the hypothesis of the participation of SOX9 in the pathogenesis of the clinical features of syndromic and nonsyndromic PRS. This should guide future research on the topic.

To investigate whether sodium supplementation increases weight gain in babies with grade 3 Pierre Robin sequence if their urinary sodium is low. Retrospective review of all medical, dietitian, and nursing notes of babies admitted from 2000 to 2007, inclusive. Tertiary center for cleft care. A total of 33 babies requiring nasogastric and nasopharangeal intubation for Pierre Robin sequence were identified. Those for whom weights could not be measured accurately (n = 4) were excluded from further study. Urinary sodium was low and weight gain poor in 21 of the remaining 29 babies (72%), and oral sodium supplementation was given to establish and maintain a normal urinary sodium (10 to 20 mmol/L). Mean daily weight gain. The mean daily weight gain of the 18 babies with low urinary sodium admitted in the first few days of life improved from 20 to 34 g (p < .001) following oral sodium supplementation. This gave a mean difference of 14 g (lower quartile = 6 g, upper quartile = 25 g, 95% confidence interval = 20, 90% confidence interval = 10). The mean daily weight gain of the eight patients who did not require sodium supplementation was 33.6 g. Urinary sodium tests are simple and noninvasive and allow monitoring of urinary sodium. If low, adequate supplementation improved weight gain (p < .001), reversing failure to thrive in babies with severe Pierre Robin sequence. These findings have been unreported previously.

This study analyzed in three dimensions the longitudinal growth pattern of young patients with hemifacial microsomia (HFM) before and after mandibular distraction osteogenesis (DO). Six individuals with HFM (five boys and one girl; age at distraction, 12.5 +/- 2.4 years) were treated with similar procedures (surgery, type and direction of distraction, no functional orthodontic treatment before and after DO). Two individuals who did not undergo DO until late in their growth were used to compare growth patterns. In addition, one individual besides the six previously chosen sample in whom no DO was performed was also used to compare longitudinal growth patterns. Lateral and posteroanterior (PA) cephalograms were utilized preoperatively, spanning a period of 9 years. Computerized three-dimensional models were constructed from the lateral and PA cephalograms using a vector intercept algorithm. In the comparison group, for a period of 8 years on the affected side, the ramus height, body length, and total mandibular length increased at an average rate of 1.3, 1.9, and 3.0 mm per year respectively. On the unaffected side, the ramus height increased by 2.1 mm per year, 1.9 mm in the body, and 2.9 mm per year in total mandibular length. On average, the gonial angle on the affected side was increased by 1 deg per year, yet decreased by 1 deg per year on the unaffected side. The proportions between the affected to the unaffected side were maintained. In the six individuals 18 months after DO, it was found that the ramus height was reduced by 1.0 mm, whereas the body was found to resume its growth with a faster rate on the distracted side, maintaining its proportion. Angular changes demonstrated closing of the gonial angle on both the unaffected (0.5 deg) and distracted (3.5 deg) sides. Observed in three dimensions were the following: (1) On average, unoperated patients with isolated HFM tend to maintain their asymmetrical facial proportions and do not worsen substantially with time. (2) Different treatment effects were seen on the ramus, body, and total length of the mandible: changes in body length > ramus height > total length. (3) Eighteen months after DO, the correction was stable but with some degree of settling back from the initial overcorrection (< 5%). (4) Eighteen months after DO the mandibular body was found to have greater growth than the ramus. (5) Evaluating changes in three dimensions provides an improved understanding of the growth pattern and distraction effects on the mandible and its structural components. (6) Additional studies on the effect of mandibular distraction on other conditions involving mandibular deformities are required. In addition, the effect of various distractor devices should also be evaluated. Three-dimensional evaluation is recommended for improved accuracy.