Nonsyndromic Pierre Robin Sequence Research Articles

Use of Mandibular Distraction Osteogenesis to Correct Micrognathia and Airway Obstruction in Newborn Female with Pierre Robin Sequence and Neonatal Abstinence Syndrome in Rural Appalachia

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.

The Pathogenesis of Pierre Robin Sequence through a Review of SOX9 and Its Interactions.

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.

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.

Three-dimensional comparison of mandibular morphology in young people with Treacher Collins syndrome and Pierre Robin sequence

Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS) share mandibular deficiency as a similar clinical finding. This study aimed to compare the mandibular size and morphology of subjects with TCS and PRS. Group TCS was composed of 17 subjects (7 male, 10 female) with a mean age of 11.5years (standard deviation, 4.4) from a single center. Group PRS was composed of 17 subjects paired by age and sex with group TCS. Preorthodontic cone-beam computed tomography examinations of all patients were evaluated using Mimics Innovation Suite 17.0 (Materialise, Leuven, Belgium). Nine 3-dimensional measurements were performed in segmented 3D images of the mandible. Intragroup comparisons were performed using paired t tests. Intergroup comparisons were performed using analysis of variance and Tukey tests. The significance level considered was 5%. TCS showed a significant dimensional difference between less and more affected sides for ramus, condyles, and mandibular body. The mandibular dimensions in PRS were more symmetrical. Group TCS presented a smaller mandibular effective length and mandibular body length compared with PRS. The condyle width and height and the ramus width were also decreased in TCS. The gonial angle was greater in TCS compared with the PRS group. Young subjects with TCS presented a smaller, more vertical, and more asymmetrical mandible compared with nonsyndromic PRS.

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.

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.

How Does Hypodontia Compare in Nonsyndromic Pierre Robin Sequence Versus Isolated Cleft Palate and Isolated Cleft Lip?

To assess the prevalence and patterns of hypodontia in nonsyndromic Pierre Robin sequence (PRS) and compare it with hypodontia in nonsyndromic isolated cleft palates and isolated cleft lips. Retrospective cohort study. Alder Hey Children's Hospital, United Kingdom. Patients with nonsyndromic PRS (group 1), isolated cleft palate (group 2), and isolated cleft lip (group 3). Hypodontia in the permanent dentition assessed from orthopantomographs. A total of 154 patients were included. Group 1 had the highest incidence of hypodontia with 47% having at least one tooth congenitally absent. Groups 2 and 3 had reduced rates of hypodontia with 27% and 19% of the groups missing teeth, respectively; 93% of cases of hypodontia in group 1 involved the absence of at least one second premolar. Of these patients, there was found to be bilateral agenesis of second premolars in 50% of cases. Patients with PRS and cleft palates are more likely to have hypodontia than those with isolated cleft palates or unilateral cleft lips. Patients with PRS have more severe hypodontia than those with isolated cleft palates or unilateral cleft lips. Bilateral agenesis of lower second premolars is a commonly seen pattern among patients with PRS. In this large UK study, a similar prevalence and pattern of hypodontia to other nonsyndromic PRS populations worldwide has been demonstrated.

Impact of Hospital Characteristics on Mandibular Distraction Osteogenesis Outcomes Among Patients With Pierre Robin Sequence Utilizing a National Inpatient Database.

This study collected national inpatient data to investigate the impact of hospital specialty and size on patient outcomes following mandibular distraction osteogenesis (MDO). Kids' Inpatient Database was used to identify patients less than 12 months of age with Pierre Robin sequence (PRS) who underwent MDO in one of the following years: 2006, 2009, and 2012. Inpatient database from the United States. Two hundred seventy-six patients with PRS underwent MDO with 134 (48.6%) identified as nonsyndromic and 142 (51.4%) as syndromic. Mandibular distraction osteogenesis. Length of hospital stay, adjunct airway and nutritional interventions and disposition. The average length of stay was 24 and 30 days for patients with nonsyndromic and syndromic PRS, respectively (P = .066). Patients with a syndromic as compared to nonsyndromic diagnosis had a higher incidence of gastrostomy tube placement (21.8 vs 12.7%, P = .045). Univariate analysis showed that a lower proportion of patients at children's hospitals as compared to non-children's hospitals necessitated 1 or more airway or nutrition-related intervention (19/148 [12.8%] vs 31/127 [24.4%]; P = .012) and had a lower incidence of a nonroutine discharge (transfer or patient death; 7.4% vs 40.0% nonroutine; P < .001). Multivariable analysis additionally revealed that patients at children's hospitals were less likely to discharge nonroutine (OR = 0.07, 95% CI: 0.02-0.32). Results from this national cohort demonstrated that at children-specific hospitals patients with PRS were less likely to require additional airway and nutritional procedures and more likely to discharge to home.

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.

Comparison Between Treacher Collins Syndrome and Pierre Robin Sequence: A Cephalometric Study.

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.

Weight Gain in Infants With Pierre Robin Sequence in the First Year of Life.

To compare growth trends among infants with Pierre Robin sequence (PRS) to normal World Health Organization (WHO) growth standards. Case series with chart review. Twenty-four infants with syndromic and nonsyndromic PRS (54% male) treated at an urban academic medical center between 2009 and 2017 were included. Infants with symptomatic hypoventilation underwent mandibular distraction osteogenesis (71%). Weights were recorded at roughly 1- to 3-month intervals from birth to 12 months, with ages adjusted for prematurity. The 50th percentile (P50) for this cohort was calculated and compared to WHO standards. In total, 135 weight entries for 24 subjects were included. The birth weight P50 was similar to the WHO standard (females: 0.09 kg above WHO [95% CI, -0.25 to +0.43; z score = 0.19]; males: 0.38 kg below WHO [95% CI, -0.77 to 0.00; z score = -0.79]). A slower growth rate was noted among female and male infants with PRS: in month 5, the PRS P50 among females was 1.42 kg below the WHO standard (95% CI, -1.77 to -1.07; z score = -1.64). Among males in month 3, the PRS P50 was 1.68 kg below the WHO standard (95% CI, -2.12 to -1.24; z score = -2.19). By month 12, weight deficiencies had resolved in both groups. Newborns with and without PRS may have similar birth weights, but the growth rate among male and female infants with PRS may lag behind that of unaffected infants, even when upper airway obstruction has been addressed in early infancy.

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.

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.

Pierre Robin Sequence: Incidence of Speech-Correcting Surgeries and Fistula Formation

Children with Pierre Robin sequence (PRS) and cleft palate have a high rate of velopharyngeal insufficiency (VPI) following primary palatoplasty. Our purpose was to determine the long-term incidence of speech-correcting surgeries (SCSs) and fistula rates in PRS after primary palatoplasty and the influence of possible causal factors. A retrospective single-center, observational chart review study. After exclusion, the study cohort comprised 78 nonsyndromic PRS children (48 females) born between 1990 and 2009 and treated at the Cleft Palate and Craniofacial Center of Helsinki University Hospital, Finland. Causal factors included gender, surgeon, age at primary palatoplasty, surgical technique, airway obstruction in infancy, and cleft severity. We analyzed the outcome at age 8 years and at data retrieval, with a median follow-up of 14 years (range: 8-27 years). Thirty-four (43.6%) children received SCS by age 8 years, and of the 19 (24.4%) postoperative fistulas, 6 (7.7%) underwent closure. At data retrieval, 37 (47.4%) children had undergone SCS and 8 (10.3%) had a fistula closure. Median age at SCS was 6 years. The results showed no significant association for gender, surgeon, age at primary palatoplasty, surgical technique, cleft severity, or airway obstruction in infancy regarding incidence of SCS, fistulas, or repaired fistulas. Pierre Robin sequence in children is associated with a high incidence of SCS and fistula formation, which necessitates accurate clinical follow-up and observation of speech development. The development of VPI in PRS is complex and most likely involving multiple factors.

S6B-04 SESSION 6B: HFM ROBIN - PART I QUANTIFICATION OF MANDIBULAR MORPHOLOGY IN PIERRE ROBIN SEQUENCE USING NOVEL 3-DIMENSIONAL TECHNIQUES

Introduction: Pierre Robin Sequence (PRS) is described as micrognathia, glossoptosis, and airway obstruction. Various studies utilizing anthropometric analysis, 2-dimensional CT scans and/or linear measurements produced from 3-dimensional images have sought to delineate anatomical differences of the mandible in patients with PRS. Several studies have noted micrognathia, however, no discrete quantitative measure exists defining precise measurements of mandibular morphology. The purpose of this study was to utilize 3D software to evaluate the mandibles of children diagnosed with non-syndromic Pierre Robin Sequence, producing novel measurements to determine morphologic differences compared to control patients. Methods: Patients diagnosed with non-syndromic PRS receiving a craniofacial/maxillofacial CT scan under the age of 6 months were identified. Basic demographic information was retrieved. 3D structures were created from CT scans using the Materialise Mimics Innovation Suite software. Study patients were then age and sex-matched to control patients diagnosed with normal CT scans. The mandibles were segmented from surrounding structures and a combination of linear, angular, and 3D measurements were performed. Results: A total of 31 study patients were included (average age 1.2 months) and 31 matched control patients (average age 1.7 months); 17 males and 14 females in each group. Study patients were noted to have a smaller mandibular body length by linear and 3-dimensional measurements (p < 0.05). However, a maxilla-mandibular body ratio was calculated to control for patient-specific size differences revealing an average ratio of 0.86 for both study and control patients (p > 0.05). Gonial angles were slightly narrower in study patients (-5.3o), but the intergonial angle was more obtuse (+14.3o) (p < 0.05). A ratio comparing gonial width and the distance between the gonion and menton was greater in PRS patients (p < 0.001). Conclusion: With the use of advanced technology and the advent of 3-dimensional software, we can now obtain accurate craniofacial measurements quantifying morphologic differences. This study is the first to use novel 3D measurements revealing the precise differences of non-syndromic PRS mandibles. When controlling for patient-specific dimensions, we conclude that the size of the mandible is not proportionally smaller, however, the shape is abnormal. Due to the larger intergonial angle and narrow gonial angles, the overall shape of the mandible likely contributes to glossal malposition resulting in airway obstruction. Understanding this morphological variance will assist in providing enhanced operative interventions.

S6B-15 SESSION 6B: HFM ROBIN - PART I LONG-TERM ORTHOGNATHIC CONSIDERATIONS IN THE PIERRE ROBIN SEQUENCE PATIENT

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.

Novel dental phenotype in non-syndromic Pierre Robin Sequence: A retrospective study

ObjectiveThe objective was to investigate dental phenotypes in individuals with non-syndromic Pierre Robin Sequence (ns-PRS) and compare the prevalence of these phenotypes with subjects with non-syndromic cleft palate (ns-CP) and a control group with subjects without any craniofacial anomalies. MethodsA total of 760 panoramic radiographs of 330 individuals (110 with ns-PRS; 110 with ns-CP and 110 without any malformations) were digitized and evaluated regarding the diagnosis of taurodontism, tooth agenesis, root dilaceration and tooth transposition. Chi-square test was applied to compare the occurrence of dental phenotypes between groups. A P value of less than 0.05 was considered statistically significant. ResultsTotal prevalence of dental phenotypes was 94.5% of ns-PRS; 54.5% of ns-CP and 59.1% of the control group subjects with a statistically significant difference for the ns-PRS when compared to the other two groups. Two dental phenotypes, taurodontism and dental agenesis were identified with statistically significant higher prevalences in subjects with ns-PRS when compared with the ns-CP group and the control group (p < 0.001). Taurodontism was the most prevalent dental phenotype, with 92.73% in the ns-PRS group, 40.91% for ns-CP and 44.55% in the control group. Tooth agenesis had a prevalence of 22.7% for ns-PRS, 4.5% for ns-CP and no case in the control group. For the prevalence of root dilaceration and tooth transposition, no statistically significant differences were observed between the three groups. ConclusionsDue to the high frequency of taurodontism in individuals with ns-PRS, we suggested that this novel phenotype would be important in the phenotypic screening of ns-PRS and could be considered as a phenotype associated with ns-PRS.

Pierre Robin sequence: Subdivision, data, theories, and treatment - Part 2: Syndromic and nonsyndromic Pierre Robin sequence.

Context:The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in the scientific literature, relating to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and the early management.Aims of Part 2:Contribute to the sparse scientific knowledge about pathogenesis and involved genetics.Subjects and Methods:An analysis of this large database was conducted focusing on genetic involvement, family history, and the incidence of additional syndromes.Results:Beside of differences related to clinical signs of dyspnea, feeding problems and mortality rates, various concomitant syndromes, and genetic abnormalities were found in cases of Fairbairn–Robin triad (FRT) and Siebold–Robin sequence (SRS), in addition to differences in relation to clinical signs of dyspnea, feeding problems, and mortality rates.Conclusion:Multiple FRT cases presented with various concomitant syndromes and genetic abnormalities, but only one type occurred in two SRS cases. The latter presented a significantly different mortality rate when compared to the FRT subgroup.

Multidisciplinary Aspects of 104 Patients With Pierre Robin Sequence.

To describe Pierre Robin sequence patients with a cleft palate from a multidisciplinary perspective. A total of 104 individuals with Pierre Robin sequence and cleft palate, born between 1980 and 2010. Data were collected retrospectively and compared with large control groups. Of 104 patients, 19 (18.3%) were treated with a nasopharyngeal or oropharyngeal tube, continuous positive airway pressure, and/or a tracheotomy. The mean weight percentile for newborns with Pierre Robin sequence was 30.9. It decreased to 29.9 at the time of cleft palate repair (mean age, 13.7 months) (P = .78). Of 87 patients, 30 (34.5%) developed normal speech after cleft palate repair. Of 93 nonsyndromic Pierre Robin sequence patients, 31 (33.3%) had or are having surgery for velopharyngeal insufficiency, a rate that is significantly higher when compared with a control group of cleft palate-only patients (19.4%; P = .004). Of 31 patients, 25 (80.6%) developed normal resonance after surgery for velopharyngeal insufficiency. There was no significant difference in the rate of syndromes between the Pierre Robin sequence patients and a control group of cleft palate patients without Pierre Robin sequence (P = .25). Seven of 39 boys (17.9%) with Pierre Robin sequence had a diagnosis of autism spectrum disorder. Even though the mean weight percentile for newborns with Pierre Robin sequence was low, the patients did not show a growth spurt during the first year of life. The high rate of velopharyngeal insufficiency after cleft palate repair in patients with Pierre Robin sequence needs further investigation. Also, the high rate of autism spectrum disorder among boys with Pierre Robin sequence prompts further investigation.

Prevalence and patterns of permanent tooth agenesis in patients with nonsyndromic Pierre Robin sequence

Individuals with Pierre Robin sequence (PRS) frequently have tooth agenesis, especially in the mandible. The aims of this study were to characterize permanent tooth agenesis patterns and to determine their prevalence in patients with nonsyndromic PRS. Radiographs and clinic charts of 146 children with nonsyndromic PRS were examined for permanent tooth agenesis, excluding third molars, and the tooth agenesis patterns were identified with the tooth agenesis code. The overall prevalence of permanent tooth agenesis was 32.9% (48 of 146 patients), with about two thirds having bilateral tooth agenesis. No sex or racial predilection was found for tooth agenesis. The most common tooth agenesis pattern was the absence of both mandibular second premolars. Among the children with tooth agenesis, almost half had agenesis patterns involving both mandibular second premolars. Other common patterns of permanent tooth agenesis involved the maxillary lateral incisors and the maxillary premolars. Symmetric agenesis of individual tooth types occurs much more frequently in the mandible than in the maxilla in patients with nonsyndromic PRS. Bilateral absence of the mandibular second premolars is the predominant pattern of dental agenesis.