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The Cleft Palate-craniofacial Journal :... Nov 2021Patients with Richieri-Costa-Pereira syndrome (RCPS) present severe craniofacial alterations and frequently require orthodontic and surgical procedures. Thus, this study...
OBJECTIVE
Patients with Richieri-Costa-Pereira syndrome (RCPS) present severe craniofacial alterations and frequently require orthodontic and surgical procedures. Thus, this study aims to describe the craniofacial relationships in patients with RCPS.
DESIGN
Panoramic radiographs and lateral cephalometric teleradiographs of 7 patients with RCPS and 7 age- and sex-matched nonsyndromic patients were analyzed. Cephalometric measurements were used to determine the size of apical bases, the relationship between them, the pattern of craniofacial growth, and the facial heights of the patients. Interobservers' concordance was verified by intraclass coefficient. For comparison between the groups, paired test was employed. values <.05 indicated statistical significance.
RESULTS
Average age of patients with RCPS was 18.5 years. Six patients were female. All patients with RCPS had Pierre-Robin sequence while 2 also presented cleft mandible. Most patients with RCPS had missing lower central incisors (100%), lower lateral incisors (85.7%), lower second premolars (85.7%), and/or upper lateral incisors (57.1%). Concordance between observers was excellent for all cephalometric measurements (0.87-0.99). Patients with RCPS presented severe craniofacial alterations when compared to control group: sella-nasion-B point (SNB) angle (73.8 ± 4.86 vs 78.85 ± 4.53, = .029), maxillary length (7.89 cm ± 0.58 cm vs 16.36 cm ± 0.75 cm, = .001), mandibular length (9.90 cm ± 0.46 cm vs 20.61 cm ± 0.45 cm, = .001), upper anterior face height (5.41 cm ± 0.50 cm vs 9.40 cm ± 0.47 cm, = .001), lower anterior face height (5.48 cm ± 0.75 cm vs 11.66 cm ± 0.55 cm, = .001), and posterior face height (6.70 cm ± 0.33 cm vs 13.65 cm ± 1.06 cm, = .001). There was no difference in SNB, A point-nasion-B point, pogonion-nasion-B point, and mandibular place angles between the groups ( > .05).
CONCLUSION
Patients with RCPS present deficient development of maxilla and mandible when compared with nonsyndromic patients.
Topics: Adolescent; Clubfoot; Female; Hand Deformities, Congenital; Humans; Maxilla; Pierre Robin Syndrome
PubMed: 33504197
DOI: 10.1177/1055665620987749 -
Paediatric Respiratory Reviews Mar 2023Pierre Robin Sequence (PRS) is defined by a constellation of characteristics including micrognathia, glossoptosis and airway obstruction. PRS can occur in isolation or... (Review)
Review
Pierre Robin Sequence (PRS) is defined by a constellation of characteristics including micrognathia, glossoptosis and airway obstruction. PRS can occur in isolation or can be associated with syndromes and another anomalies. Airway obstruction and feeding difficulties are the major presenting issues, and the severity of the condition ranges from mild, with minimal to no symptoms, to severe, with overt obstruction resulting in apnoeas, severe respiratory distress and cyanosis. The presence of airway obstruction can result in obstructive sleep apnoea and abnormalities in gas exchange, as well as exacerbation of already present feeding difficulties and failure to thrive, secondary to mismatch of caloric intake to energy usage associated with increased effort of breathing. Management of airway obstruction for infants with PRS varies between centres. This paper explores the surgical and non-surgical management options available, their effectiveness and pitfalls in children with PRS. Despite the pros and cons of each management option, it is evident that resource availability and multidisciplinary clinical support are key factors to successful management.
Topics: Infant; Child; Humans; Pierre Robin Syndrome; Osteogenesis, Distraction; Airway Obstruction; Sleep Apnea, Obstructive; Dyspnea; Treatment Outcome
PubMed: 35987882
DOI: 10.1016/j.prrv.2022.07.001 -
Journal of Developmental Biology Dec 2020The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory... (Review)
Review
The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory obstruction, and in some cases, cleft palate. A causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated gene expression, precise cellular processes, pathogenesis, and PR-associated anomalies are documented. This review presents the current understanding of PR phenotypes, the proposed pathogenetic processes underlying them, select genes associated with PR, and available animal models that could be used to better understand the genetic basis and phenotypic variation of PR.
PubMed: 33291480
DOI: 10.3390/jdb8040030 -
Molecular Cell May 2023Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate SOX9 expression at genomic distances over 1.25 Mb. We applied...
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.
Topics: Humans; Chromatin; Regulatory Sequences, Nucleic Acid; Promoter Regions, Genetic; Gene Expression Regulation; Genome; Cell Cycle Proteins; Enhancer Elements, Genetic; CCCTC-Binding Factor
PubMed: 36996812
DOI: 10.1016/j.molcel.2023.03.009 -
The Journal of Craniofacial Surgery 2020The aim of this study was to evaluate pre-operative nutritional status, associated syndromes and abnormalities, and post-operative outcomes of patients with Pierre Robin...
INTRODUCTION
The aim of this study was to evaluate pre-operative nutritional status, associated syndromes and abnormalities, and post-operative outcomes of patients with Pierre Robin Sequence (PRS) versus those with non-syndromic isolated cleft palate (CIP).
METHODS
Between January 1995 and December 2013, patients with a cleft palate Veau I-II according to the Veau classification with and without PRS who underwent primary repair were retrospectively analyzed. The nutrition status, age at the time of palatoplasty, additional anomalies, gestational complications, and post-operative speech abnormalities and outcomes were evaluated.
RESULTS
A total of 59 patients with PRS (PRS group) and 132 patients without PRS (non-PRS group) were included in the study. Of all patients, 92 were males and 99 were females with a mean age of 14 ± 4.18 (range, 6 to 26) years. The rate of gestational complications, enteral nutrition, complete cleft, additional anomalies, and velopharyngeal insufficiency was significantly higher in the PRS group (P < 0.05). However, the incidence of fistulas and age at the time of palatoplasty did not significantly differ between the groups.
CONCLUSION
Based on our study results, enteral nutrition, respiratory problems, pregnancy complications, velopharyngeal insufficiency, and additional anomalies, but not post-operative palatal fistulas, are more frequently seen in patients with PRS. Although pre-operative care and treatment and rehabilitation in patients with PRS are more complicated than those with the CIP, our experience demonstrates that meticulous repair and follow-up can minimize complications, such as fistulas.
Topics: Adolescent; Adult; Child; Cleft Palate; Female; Fistula; Humans; Incidence; Male; Pierre Robin Syndrome; Postoperative Complications; Postoperative Period; Retrospective Studies; Speech Disorders; Treatment Outcome; Velopharyngeal Insufficiency; Young Adult
PubMed: 31725501
DOI: 10.1097/SCS.0000000000005961 -
Plastic and Reconstructive Surgery Feb 2022Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies... (Observational Study)
Observational Study
BACKGROUND
Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years.
METHODS
All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes.
RESULTS
Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p < 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate (p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate-only group. Statistical analysis revealed no significant effect of group (Z = -1.47; p = 0.14).
CONCLUSIONS
No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, II.
Topics: Child; Child Development; Child, Preschool; Cleft Palate; Female; Humans; Male; Pierre Robin Syndrome; Prospective Studies; Speech; Speech Disorders
PubMed: 34898524
DOI: 10.1097/PRS.0000000000008730 -
Journal of Community Genetics Oct 2020Pierre Robin sequence (PRS) is a craniofacial abnormality comprising micrognathia, glossoptosis and airway obstruction, which can impair the newborn's feeding and...
Pierre Robin sequence (PRS) is a craniofacial abnormality comprising micrognathia, glossoptosis and airway obstruction, which can impair the newborn's feeding and breathing. While there has been much research around the cause of PRS and most appropriate methods of care, understanding the psychosocial aspects of a PRS diagnosis from the parents' perspective is lacking. The aim of this study is to understand parental experiences of having a child diagnosed with PRS, as well as the role of genetic counselling in PRS. Fourteen semi-structured interviews were conducted with parents of children diagnosed with isolated PRS between 2 and 5 years prior. From these 14 interviews, eleven transcripts were analysed to find common themes and experiences. The diagnosis was confusing and overwhelming for participants during emotionally sensitive periods and little was understood about the cause of their child's PRS. Those participants who did recall experiences with genetic services reported that they were minimal and uninformative. According to participant recollection, genetic counselling was rarely offered, despite there being a potential for this service in PRS. Genetic counselling would be a valuable source of information and support for parents both at the time of antenatal diagnosis, and potentially 6 to 12 months later in the outpatient environment when these children are all routinely reviewed by their clinical care team.
PubMed: 32372164
DOI: 10.1007/s12687-020-00466-4 -
Plastic and Reconstructive Surgery Mar 2021Pierre Robin sequence (Robin sequence) is defined as the triad of micrognathia, glossoptosis, and airway obstruction. It is frequently associated with palatal clefting....
BACKGROUND
Pierre Robin sequence (Robin sequence) is defined as the triad of micrognathia, glossoptosis, and airway obstruction. It is frequently associated with palatal clefting. In recent years, increased interest in speech outcomes of cleft patients diagnosed with Robin sequence has been shown.
METHODS
Speech outcomes of cleft patients with Robin sequence were assessed at age 5 in comparison with a cleft palate-only cohort. Speech parameters were evaluated according to the Cleft Audit Protocol for Speech-Augmented and analyzed using the National Audit Standards for Speech (United Kingdom). All patients were treated in the same institution during the same period (2005 to 2012). Subjects who needed nasopharyngeal airway support and those whose airway was managed by positioning only were eligible.
RESULTS
Fifty-one cleft patients diagnosed with Robin sequence were included in this study. Outcomes were compared to those of 128 nonsyndromic cleft palate-only patients.Patients with Robin sequence were shown to present with a significantly higher rate of cleft speech characteristics in comparison to the reference cohort (p = 0.001). Furthermore, it was shown that Robin sequence is associated with a significantly higher rate of secondary speech surgery for velopharyngeal dysfunction before the age of 5 (p = 0.016). Robin sequence patients with a nasopharyngeal airway presented with a higher rate of cleft speech characteristics compared to Robin sequence patients managed with positioning only.
CONCLUSION
Cleft patients with Robin sequence are more likely to need further surgery to correct velopharyngeal dysfunction before the age of 5 and are more prone to present with cleft speech characteristics at the age of 5.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, II.
Topics: Case-Control Studies; Child; Child, Preschool; Cleft Palate; Female; Humans; Male; Pierre Robin Syndrome; Plastic Surgery Procedures; Severity of Illness Index; Speech; Speech Disorders; Treatment Outcome; Velopharyngeal Insufficiency
PubMed: 33587554
DOI: 10.1097/PRS.0000000000007641 -
Plastic and Reconstructive Surgery.... Apr 2022The 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...
UNLABELLED
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.
PubMed: 35415063
DOI: 10.1097/GOX.0000000000004241 -
The Journal of Craniofacial SurgeryAirway obstruction in newborns with Pierre Robin sequence (PRS) may be managed with tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), or tracheostomy...
OBJECTIVE
Airway obstruction in newborns with Pierre Robin sequence (PRS) may be managed with tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), or tracheostomy to prevent airway compromise when conservative airway interventions fail or are contraindicated based on the type of obstruction present. Unfortunately, some of these procedures have the potential to affect a child's speech and feeding development.
METHOD
The authors retrospectively reviewed the records of all children with PRS treated at our institution in the last 25 years. Our primary outcomes of interests were: (1) consonant production errors; (2) achievement of full oral feeds; (3) need for prolonged gastrostomy tube feeds; and (4) avoidance of tracheostomy.
RESULTS
Seven (7/73, 10%) children required intubation at birth for respiratory failure. Forty-two children were treated with TLA (42/73, 58%), 2 with MDO (2/73, 3%), and 1 (1/73, 1%) with tracheostomy. Twenty-one (21/73, 29%) were treated with conservative airway interventions. Of the 7 children requiring intubation, 1 required tracheostomy, and 6 required TLA. Five children who received TLA initially proceeded to tracheostomy. Of the 3 children who underwent MDO, 2 required tracheostomy. Of the 2 patients who underwent MDO, 2 failed, requiring tracheostomy. One child required tracheostomy as the first airway intervention. Among all children with PRS, /s,z/ speech errors were the most common. Children treated with conservative airway interventions had significantly fewer /sh/ errors at age 3 (X = 6.604, P < 0.05) relative to those treated with TLA, MDO, and/or tracheostomy. Consonant production errors extinguished over time, with significantly less /s,z/ errors produced at age 8 compared to at ages 3 (Z = -2.263, P < 0.01), 4 (Z = -2.449, P < 0.05), 5 (Z = -2.775, P < 0.01), and 6 (Z = -2.049, P < 0.05). Among all children, 70% (51/70) were able to achieve full oral feeds.
CONCLUSIONS
This study describes speech-production and feeding outcomes in children with PRS. Tongue-tip sound errors, including /s,z/, are prominent early in speech development but later extinguish, a pattern of speech maturation that follows that of typically-developing children.Most children were able to achieve full oral feeds, with few requiring prolonged g-tube placement. We hope these results serve as a useful tool in managing speech and feeding in children with TLA, and when counselling patients with PRS requiring definitive airway surgery.
Topics: Airway Obstruction; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Retrospective Studies; Speech; Tongue Diseases; Treatment Outcome
PubMed: 34608009
DOI: 10.1097/SCS.0000000000008232