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Science Advances Nov 2022Aberrations in tissue-specific enhancers underlie many developmental defects. Disrupting a noncoding region distal from the human gene causes the Pierre Robin sequence...
Aberrations in tissue-specific enhancers underlie many developmental defects. Disrupting a noncoding region distal from the human gene causes the Pierre Robin sequence (PRS) characterized by the undersized lower jaw. Such a craniofacial-specific defect has been previously linked to enhancers transiently active in cranial neural crest cells (CNCCs). We demonstrate that the PRS region also strongly regulates in CNCC-derived Meckel's cartilage (MC), but not in limb cartilages, even after decommissioning of CNCC enhancers. Such an MC-specific regulatory effect correlates with the MC-specific chromatin contacts between the PRS region and , highlighting the importance of lineage-dependent chromatin topology in instructing enhancer usage. By integrating the enhancer signatures and chromatin topology, we uncovered >10,000 enhancers that function differentially between MC and limb cartilages and demonstrated their association with human diseases. Our findings provide critical insights for understanding the choreography of gene regulation during development and interpreting the genetic basis of craniofacial pathologies.
Topics: Humans; Chromatin; Pierre Robin Syndrome; Enhancer Elements, Genetic; Cartilage
PubMed: 36417512
DOI: 10.1126/sciadv.abo3648 -
Plastic and Reconstructive Surgery Nov 2020One 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."...
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, II.
Topics: Adolescent; Cephalometry; Cleft Palate; Conservative Treatment; Female; Follow-Up Studies; Humans; Male; Malocclusion, Angle Class II; Mandible; Orthognathic Surgical Procedures; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 33136957
DOI: 10.1097/PRS.0000000000007246 -
Seminars in Fetal & Neonatal Medicine Dec 2021Robin sequence (RS) is a heterogeneous congenital condition characterized by retrognathia, glossoptosis, upper airway obstruction, and very often, posterior U-shape... (Review)
Review
Robin sequence (RS) is a heterogeneous congenital condition characterized by retrognathia, glossoptosis, upper airway obstruction, and very often, posterior U-shape cleft palate. Half the children with RS have an underlying syndrome, either identified (syndromic RS) or not (RS+). Long-term intellectual developmental outcome first depends on the underlying diagnosis and is often poor in syndromic cases. On the contrary, the rare studies that analysed the long-term developmental outcome of children with isolated RS who received effective treatment of their respiratory and feeding difficulties early in life, showed intellectual and academic results close to or within the normal range. Speech outcome in RS is often delayed with phonation disorders. Speech difficulties depend on intellectual level, hearing and velar function after palate repair. It affects most children with RS and deserves active monitoring and care.
Topics: Child; Cleft Palate; Humans; Pierre Robin Syndrome; Respiration Disorders; Retrospective Studies; Treatment Outcome
PubMed: 34561179
DOI: 10.1016/j.siny.2021.101286 -
The Journal of Craniofacial Surgery May 2021This cohort study aimed to assess how age at repair affects outcomes in nonsyndromic patients with and without Robin Sequence using a national database of commercial...
BACKGROUND
This cohort study aimed to assess how age at repair affects outcomes in nonsyndromic patients with and without Robin Sequence using a national database of commercial healthcare claims.
METHODS
Children under 4 years of age undergoing palatoplasty were identified in the IBM MarketScan Commercial Database based on ICD-9-CM and CPT procedure codes. They were divided into Robin and non-Robin cleft palate groups, and further divided by time of initial cleft palate repair: Robin Sequence into 2 groups: age ≤10 months or >10 months; non-Robin cleft palate into 3 groups: age ≤10 months, >10-14 months, or >14 months age. Time to cleft palate revision within each group was assessed using Cox proportional-hazard models.
RESULTS
A total of 261 patients with Robin Sequence and 3046 with non-Robin cleft palate were identified. In patients with Robin, later repair was associated with decreased risk of secondary procedures compared with early repair (Hazard Ratio (HR) 0.19, 95%CI 0.09-0.39, P < 0.001). In patients with non-Robin cleft palate, decreased risk of revision compared to early repair was associated both with repair at >10-14 months (adjusted HR 0.40, 95%CI 0.31-0.52, P < 0.001) and > 14 months (adjusted HR 0.71, 95%CI 0.57-0.88, P = 0.002). Adjusting for timing of repair, patients with non-Robin cleft palate were at significantly increased risk of secondary procedure if diagnosed with failure to thrive or anemia in the 30 days prior to palatoplasty.
CONCLUSIONS
In patients with and without Robin sequence, cleft palate repair at or before 10 months of age was associated with higher risk for secondary procedures.
Topics: Child; Child, Preschool; Cleft Palate; Cohort Studies; Humans; Infant; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome
PubMed: 33290333
DOI: 10.1097/SCS.0000000000007311 -
Plastic and Reconstructive Surgery Jun 2022The timing of extubation following placement of mandibular distractors in the setting of Pierre Robin sequence is variable across institutional algorithms. Postoperative...
BACKGROUND
The timing of extubation following placement of mandibular distractors in the setting of Pierre Robin sequence is variable across institutional algorithms. Postoperative maintenance of intubation allows for an improvement in airway dimension and tongue positioning before extubation, theoretically decreasing the impact of postoperative airway edema. Maintenance of intubation, however, is not without risk. The authors analyze their institutional experience with neonatal mandibular distraction followed by immediate extubation to assess feasibility and safety profiles.
METHODS
A 4-year retrospective review of patients diagnosed with Pierre Robin sequence who underwent mandibular distraction within the first 3 months of life was performed. Patients intubated preoperatively were excluded.
RESULTS
Fifty-two patients met inclusion criteria. Thirty-eight patients (73 percent) were extubated immediately, whereas 14 patients (27 percent) remained intubated. No differences between these groups were found when comorbidities, cleft pathology, preoperative respiratory support, or grade of view on direct laryngoscopy were analyzed. Case duration greater than 120 minutes, operation start time after 3 pm, and the subjective designation of a difficult airway by the anesthesiologist were associated with maintaining intubation (p < 0.05). Eight patients (21 percent) in the extubated group required an increase in respiratory support in the postoperative interval. Four of these patients (11 percent) required reintubation. Increased postoperative respiratory support was more likely in patients with certain comorbidities and higher preoperative respiratory support requirements (p < 0.05).
CONCLUSIONS
The authors' data suggest that immediate extubation following neonatal mandibular distraction is feasible in patients who are not intubated preoperatively. Careful consideration should be given to patients who require significant respiratory support preoperatively and in those with certain comorbidities.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, III.
Topics: Airway Extubation; Airway Obstruction; Humans; Infant; Infant, Newborn; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome
PubMed: 35413037
DOI: 10.1097/PRS.0000000000009141 -
The British Journal of Oral &... Sep 2023Pierre Robin Sequence (PRS) is a congenital craniofacial anomaly distinguished by the presence of micrognathia, glossoptosis, and upper airway obstruction. Cleft palate... (Review)
Review
Pierre Robin Sequence (PRS) is a congenital craniofacial anomaly distinguished by the presence of micrognathia, glossoptosis, and upper airway obstruction. Cleft palate occurs in over 3/4 of patients with PRS. The wide U-shape cleft and airway dysfunction create challenges in clinical management. Currently, disputes exist on the treatment protocol and prognosis of cleft palate management among patients with PRS. This review is focused on the deformity features, intervention timing, technique selection, airway support, and outcome evaluation of cleft palate among patients with PRS, aiming to provide reference to further evolution in the management of PRS-related cleft palate.
Topics: Humans; Cleft Palate; Airway Obstruction; Pierre Robin Syndrome; Prognosis; Outcome Assessment, Health Care
PubMed: 37453893
DOI: 10.1016/j.bjoms.2023.06.003 -
International Journal of Pediatric... Apr 2020Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current...
OBJECTIVES
Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current literature reports that Stickler syndrome is the most common syndrome associated with PRS, and 22q11 deletion syndrome (22q11 DS) as the second most common. This study identifies associations between PRS and genetic syndromes.
METHODS
A retrospective chart review was performed to identify patients diagnosed with PRS over a 10-year period from 4/1/2007 to 4/1/2017 at a tertiary children's hospital.
RESULTS
4,052 consecutive charts were reviewed and 234 patients had a diagnosis of PRS confirmed with the triad of micrognathia, glossoptosis, and airway obstruction. Of note, all of these patients had cleft palate. Of the 234 patients with PRS, 65 patients had syndromic diagnoses (28%). One patient had 22q11 DS (0.43%), and 31 patients had Stickler syndrome (13.2%). Additionally, 3 patients had central hypoventilation syndrome, 3 patients had Duane syndrome, 2 patients had Cornelia de Lange syndrome, 2 patients had Emanuel syndrome, 2 patients had Gordon syndrome, 2 patients had Mobius syndrome, 2 patients had Nager syndrome. Multiple other syndromes were identified, but occurred in isolated cases.
CONCLUSION
This study supports literature that PRS is most commonly associated with Stickler Syndrome but rarely associated with 22q11 DS given that only 1 patient had both PRS and 22q11 DS.
Topics: 22q11 Deletion Syndrome; Adolescent; Arthritis; Arthrogryposis; Child; Child, Preschool; Chromosome Disorders; Cleft Palate; Clubfoot; Connective Tissue Diseases; De Lange Syndrome; Duane Retraction Syndrome; Female; Hand Deformities, Congenital; Hearing Loss, Sensorineural; Heart Defects, Congenital; Humans; Hypoventilation; Infant; Infant, Newborn; Intellectual Disability; Male; Mandibulofacial Dysostosis; Mobius Syndrome; Muscle Hypotonia; Pierre Robin Syndrome; Retinal Detachment; Retrospective Studies; Sleep Apnea, Central
PubMed: 31927149
DOI: 10.1016/j.ijporl.2019.109842 -
Journal of Cranio-maxillo-facial... Jun 2020To determine weight gain during treatment with the modified palatal plate (MPP) in infants with isolated and syndromic Pierre Robin Sequence (PRS) suffering from...
OBJECTIVE
To 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.
METHODS
The 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.
RESULTS
14 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.
CONCLUSION
PRS 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.
Topics: Airway Obstruction; Child; Humans; Infant; Osteogenesis, Distraction; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome; Weight Gain
PubMed: 32317138
DOI: 10.1016/j.jcms.2020.03.009 -
Archives of Disease in Childhood Oct 2021Obstructive sleep apnoea (OSA) and feeding difficulties are key problems for Pierre Robin sequence (PRS) infants. OSA management varies between treatment centres. Sleep...
INTRODUCTION
Obstructive sleep apnoea (OSA) and feeding difficulties are key problems for Pierre Robin sequence (PRS) infants. OSA management varies between treatment centres. Sleep positioning represents the traditional OSA treatment, although its effectiveness remains insufficiently evaluated.
DESIGN
To complete a polysomnographic (PSG) evaluation of effect of sleep position on OSA in PRS infants less than 3 months of age. We analysed a 10-year national reference centre dataset of 76 PRS infants. PSG was performed as daytime recordings for 67 in the supine, side and prone sleeping position when possible. In most cases, recording included one cycle of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in each position.
RESULTS
One-third of infants (9/76, 12%) had severe OSA needing treatment intervention prior to PSG. During PSG, OSA with an obstructive apnoea and hypopnoea index (OAHI) >5 per hour was noted in 82% (55/67) of infants. OSA was most severe in the supine and mildest in the side or in the prone positions. The median OAHI in the supine, side and prone positions were 31, 16 and 19 per hour of sleep (p=0.003). For 68% (52/67) of the infants, either no treatment or positional treatment alone was considered sufficient.
CONCLUSIONS
The incidence of OSA was 84% (64/76) including the nine infants with severe OSA diagnosed prior to PSG. For the most infants, the OSA was sleep position dependent. Our study results support the use of PSG in the evaluation of OSA and the use of sleep positioning as a part of OSA treatment.
Topics: Body Height; Body Weight; Child Development; Continuous Positive Airway Pressure; Female; Humans; Infant; Infant, Newborn; Male; Patient Positioning; Pierre Robin Syndrome; Polysomnography; Prone Position; Retrospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive; Supine Position
PubMed: 34244167
DOI: 10.1136/archdischild-2020-320527 -
Clinical Oral Investigations Jul 2017In addition to breathing problems, patients with Robin sequence (RS) often encounter feeding difficulties (FD). Data regarding the occurrence of FD and possible... (Review)
Review
OBJECTIVES
In addition to breathing problems, patients with Robin sequence (RS) often encounter feeding difficulties (FD). Data regarding the occurrence of FD and possible influencing factors are scarce. The study aim was to elucidate these factors to improve treatment strategies.
MATERIAL AND METHODS
A retrospective comparative cohort study was conducted, consisting of 69 infants diagnosed with both RS and a cleft palate and 64 isolated cleft palate only (iCPO) infants. Data regarding FD, growth, and airway intervention were collected during the first 2 years of life. A systematic review of the literature was conducted to identify reported FD in RS patients.
RESULTS
RS patients had more FD (91 %) than iCPO patients (72 %; p = 0.004). Also, nasogastric (NG)-tube feeding was necessary more frequently and for a longer period (both p < 0.001). Growth was lower in RS than iCPO infants (p = 0.008) and was not affected by the kind of airway management (conservative/surgical; p = 0.178), cleft palate grade (p = 0.308), or associated disorders (p = 0.785). By contrast, surgical intervention subtype did significantly affect growth. Mean reported FD for RS in the literature is 80 % (range = 47-100 %), and 55 % (range = 11-100 %) of infants need NG-tube feeding.
CONCLUSIONS
FD is present in a large proportion of infants with RS, which indicates the need for early recognition and proper treatment to ensure optimal growth. Growth during the first 2 years of life is significantly lower in RS patients than iCPO patients, which indicates the need for careful attention and long-term follow-up.
CLINICAL RELEVANCE
This study indicates the need for early recognition and proper treatment of FD in RS to ensure optimal growth. In addition, growth needs careful attention and long-term follow-up.
Topics: Child Development; Cleft Lip; Cleft Palate; Feeding and Eating Disorders; Female; Humans; Infant; Male; Pierre Robin Syndrome; Retrospective Studies
PubMed: 27868158
DOI: 10.1007/s00784-016-1996-8