Incidence, Characteristics, and Outcomes of Robin Sequence: A Population-Based Analysis in the United States.

INTRODUCTION: While the literature is replete of clinical studies reporting on the Robin sequence (RS), population-based analyses are scarce with significant variability within the literature in terms of reported incidence, demographic parameters, and outcomes. The authors have conducted a 20-year population-based analysis to guide clinical practice. METHODS: A birth cohort was created from the available datasets in the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID; 2000-2019). Robin sequence patients were identified and further stratified by syndromic status. Incidence, demographic parameters, and outcomes including mortality and tracheostomy rates were computed. A subset analysis comparing the isolated and syndromic cohorts was conducted. Data was analyzed through a χ 2 or t test. RESULTS: The incidence of RS was 5.15:10,000 (95% CI: 4.99-5.31) from a birth cohort of 7.5 million. Overall, 63.3% of the cohort was isolated RS and 36.7% had syndromic RS. Robin sequence patients had a significantly higher rate of cardiac (25.9%) and neurological (8.6%) anomalies compared with the general birth cohort and were most commonly managed in urban teaching hospitals ( P <0.0001). The pooled mortality and tracheostomy rates were 6.6% and 3.6%, respectively. Syndromic status was associated with a longer length of hospital stay (27.8 versus 13.6 d), tracheostomy rate (6.2% versus 2.1%), and mortality (14.1% versus 2.2%) compared with isolated RS ( P <0.0001). CONCLUSIONS: The true incidence of RS is likely higher than previously reported estimates. Isolated RS patients have a low associated mortality and tracheostomy rate and are typically managed in urban teaching hospitals. Syndromic status confers a higher mortality rate, tracheostomy rate, and length of stay compared with nonsyndromic counterparts.

Global birth prevalence of Robin sequence in live-born infants: a systematic review and meta-analysis.

Robin sequence (RS), a congenital disorder of jaw maldevelopment and glossoptosis, poses a substantial healthcare burden and has long-term health implications if airway obstruction is suboptimally treated. This study describes the global birth prevalence of RS and investigates whether prevalence estimates differ by geographical location, ethnicity or study data source (registry versus non-registry data). The protocol was prospectively registered with PROSPERO.Databases were searched using keywords and subject terms for "Robin sequence", "epidemiology", "incidence" and "birth prevalence". Meta-analysis was performed fitting random effects models with arcsine transformation.From 34 eligible studies (n=2722 RS cases), pooled birth prevalence was 9.5 per 100 000 live births (95% CI 7.1-12.1) with statistical heterogeneity. One third of studies provided a case definition for RS and numerous definitions were used. A total of 22 countries were represented, predominantly from European populations (53% of studies). There was a trend towards higher birth prevalence in European populations and lower prevalence from registry-based studies. Only two studies reported ethnicity.This study indicates that RS occurs globally. To investigate geographical differences in prevalence, additional studies from non-European populations and reporting of ethnicity are needed. Heterogeneity of estimates may be due to variable diagnostic criteria and ascertainment methods. Recently published consensus diagnostic criteria may reduce heterogeneity among future studies.

Associated anomalies in Pierre Robin sequence.

Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in the reported studies. The aims of this report was to study the types and the prevalence of the anomalies co-occurring with PRS in a well-studied population northeastern France. The types and the prevalence of anomalies co-occurring in cases with PRS were ascertained in all terminations of pregnancy, stillbirths and live births in 387,067 births occurring consecutively during the period 1979-2007 in the area covered by our registry of congenital anomalies which is population-based, 89 cases of PRS were registered during the study period with a prevalence of 2.29 per 10,000 births, 69.7% of the cases had associated non-PRS anomalies. Chromosomal abnormalities were present in 10 (11.2%) cases including three 22 q11.2 deletion. Non-chromosomal recognizable conditions were diagnosed in 27 cases (30.3%) including 10 Stickler syndrome, 8 Treacher Collins syndrome, 3 cases with short stature and 6 other syndromes. Multiple congenital anomalies (MCA) were present in 25 cases (28.1%). The most frequent MCA were in the ear, face and neck (35 out of 98 anomalies, 35.7%), cardiovascular (18 anomalies, 18.4%), musculoskeletal (11 anomalies, 11.2%), central nervous (7 anomalies, 7.1%), urinary (6 anomalies, 6.1%), and eye (6 anomalies, 6.1%) system. The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with PRS.

Epidemiology of Robin sequence in the UK and Ireland: an active surveillance study.

BACKGROUND: Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000-14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth. OBJECTIVES: To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment. METHODS: Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points. RESULTS: 173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone. CONCLUSIONS: Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence.

Study protocol for a multicenter, multinational, observational registry of epidemiology, treatment and outcome of patients with Robin sequence.

BACKGROUND: Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis and upper airway obstruction. Diagnosis and treatment are characterized by heterogeneity, resulting in a lack of uniformly collected data. METHODS: We have set up a prospective, observational, multicenter, multinational registry aimed at obtaining routine clinical data from RS patients receiving different treatment approaches and enabling an assessment of outcomes obtained through different therapeutic approaches. Patient enrolment has started in January 2022. Disease characteristics, adverse events and complications depending on the different diagnostic and treatment approaches and their effects on neurocognition, growth, speech development and hearing outcome are evaluated using routine clinical data. In addition to characterizing the patient population and comparing outcomes achieved with different treatment approaches, the registry will evolve to focus on endpoints such as quality of life and long-term developmental status. DISCUSSION: This registry will provide data on different treatment approaches collected during routine care with diverse framework conditions and will allow assessing diagnostic and therapeutic outcomes of children with RS. These data, urgently demanded by the scientific community, may contribute to refining and personalizing existing therapeutic approaches and increase knowledge about the long-term outcome of children born with this rare condition. TRIAL REGISTRATION: DRKS00025365.

Syndromes associated with Robin sequence: a national prospective cohort study.

OBJECTIVES: To determine the prevalence of syndromic Robin sequence (RS) in the UK and if this group of patients had an increased need for airway and feeding management compared with a non-syndromic RS cohort. DESIGN: A prospective national multicentre study of cases submitted to the Cleft Collective cohort studies. SETTING: Specialist cleft services in the UK. PATIENTS: 259 participants who fulfilled the diagnosis of RS. This group was compared with 548 participants with cleft palate only (CPO). MAIN OUTCOME MEASURES: The primary outcome measure was the presence of a syndrome in patients with RS and CPO. Secondary outcome measures included the use of airway and feeding adjuncts. RESULTS: An associated syndrome was seen in 28% of patients with RS and 14% of patients with CPO. The most common syndrome for the RS group was Stickler syndrome (27%). Syndromic status was significantly higher among patients with RS compared with those with CPO (OR 2.36, 95% CI 1.65 to 3.39; p<0.001). Patients with syndromic RS have an increased reliance on airway adjuncts compared with the patients without syndromic RS (OR 2.02, 95% CI 1.13 to 3.64; p=0.018). There was no evidence of a difference in the use of feeding adjuncts between syndromic and non-syndromic RS groups (OR 2.43, 95% CI 0.78 to 7.58; p=0.126). CONCLUSION: The presence of a syndrome has implications for management of patients with RS. Early identification of a syndrome may help prevent the consequences of a missed syndromic diagnosis. Routine ophthalmological and genetic screening for Stickler syndrome should be mandatory for all patients with RS.

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

OBJECTIVE: 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. DESIGN: Retrospective cohort study. SETTING: Alder Hey Children's Hospital, United Kingdom. PATIENTS: Patients with nonsyndromic PRS (group 1), isolated cleft palate (group 2), and isolated cleft lip (group 3). MAIN OUTCOME MEASURES: Hypodontia in the permanent dentition assessed from orthopantomographs. RESULTS: 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. CONCLUSIONS: 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.

Robin sequence without cleft palate: Genetic diagnoses and management implications.

Robin sequence (RS), the triad of micrognathia, glossoptosis, and airway obstruction, is a major cause of respiratory distress and feeding difficulties in neonates. Robin sequence can be associated with other medical or developmental comorbidities in ~50% of cases ("syndromic" RS). As well, RS is variably associated with cleft palate (CP). Previous studies have not investigated differences in clinical characteristics of children with RS based on presence or absence of CP. We retrospectively reviewed 175 children with RS and compared genetic diagnoses, medical and developmental comorbidities, severity of airway obstruction, and feeding outcomes between those with and without CP. Strikingly, 45 of 45 (100%) children with RS without CP were classified as syndromic due to presence of comorbidities unrelated to RS, while 83 of 130 (64%) children with RS with CP were classified as syndromic. Among 128 children with syndromic RS, there were no differences in severity of airway obstruction, surgical intervention rate or type, or feeding outcome at 12 months based on CP status. Our findings support the conclusion that the pathogenesis of RS without CP is distinct from RS with CP and more likely to cause additional medical or developmental problems. Alternatively, children with RS without CP and without additional anomalies present may be under recognized.

Epidemiology of Pierre-Robin sequence in Europe: A population-based EUROCAT study.

BACKGROUND: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. OBJECTIVE: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. METHODS: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. RESULTS: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%). CONCLUSIONS: This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS.

Stickler Syndrome: Airway Complications in a Case Series of 502 Patients.

BACKGROUND: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and complications in a nonselected series of Stickler syndrome cases. To our knowledge, this is the largest such series in the published literature. METHODS: We retrospectively identified patients with genetically confirmed Stickler syndrome who had undergone general anesthesia in a major teaching hospital, seeking to identify factors that predicted patients who would require more than 1 attempt to correctly site an endotracheal tube (ETT) or supraglottic airway device (SAD). Patient demographics, associated factors, and anesthetic complications were collected. Descriptive statistical analysis and logistic regression modeling were performed. RESULTS: Five hundred and twoanesthetic events were analyzed. Three hundred ninety-five (92.7%) type 1 Stickler and 63 (96.9%) type 2 Stickler patients could be managed with a single attempt of passing an ETT or SAD. Advanced airway techniques were required on 4 occasions, and we report no major complications. On logistic regression, modeling receding mandible (P = .0004) and history of cleft palate (P = .0004) were significantly associated with the need for more than 1 attempt at airway manipulation. CONCLUSIONS: The majority of Stickler patients can be anesthetized safely with standard management. If patients have a receding mandible or history of cleft, an experienced anesthetist familiar with Stickler syndrome should manage the patient. We recommend that patients identified to have a difficult airway wear an alert bracelet.

Methadone, Pierre Robin sequence and other congenital anomalies: case-control study.

OBJECTIVE: Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS. DESIGN/SETTING: This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011. PATIENTS: Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview. RESULTS: Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2). CONCLUSIONS: These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.

Femoral-facial syndrome: A review of the literature and 14 additional patients including a monozygotic discordant twin pair.

Femoral-facial syndrome (FFS, OMIM 134780), also known as femoral hypoplasia-unusual face syndrome, is a rare sporadic syndrome associated with maternal diabetes, and comprising femoral hypoplasia/agenesis and a distinct facies characterized by micrognathia, cleft palate, and other minor dysmorphisms. The evaluation of 14 unpublished Brazilian patients, prompted us to make an extensive literature review comparing both sets of data. From 120 previously reported individuals with FFS, 66 were excluded due to: not meeting the inclusion criteria (n = 21); not providing sufficient data to ascertain the diagnosis (n = 29); were better assigned to another diagnosis (n = 3); and, being fetuses of the second trimester (n = 13) due to the obvious difficult to confirm a typical facies. Clinical-radiological and family information from 54 typical patients were collected and compared with the 14 new Brazilian patients. The comparison between the two sets of patients did not show any relevant differences. Femoral involvement was most frequently hypoplasia, observed in 91.2% of patients, and the typical facies was characterized by micrognathia (97%), cleft palate (61.8%), and minor dysmorphisms (frontal bossing 63.6%, short nose 91.7%, long philtrum 94.9%, and thin upper lip 92.3%). Clubfoot (55.9%) was commonly observed. Other observed findings may be part of FFS or may be simply concurrent anomalies since maternal diabetes is a common risk factor. While maternal diabetes was the only common feature observed during pregnancy (50.8%), no evidence for a monogenic basis was found. Moreover, a monozygotic discordant twin pair was described reinforcing the absence of a major genetic factor associated with FFS.

Epidemiology of Robin sequence with cleft palate in the East of Scotland between 2004 and 2013.

BACKGROUND: Robin sequence (RS) is a congenital disorder characterized by cleft palate, micrognathia, and glossoptosis which can result in clinically significant upper airway obstruction (UAO). Historically, incidence of RS in the UK has been estimated as 1 in 8500 live births. Our study describes birth prevalence, clinical characteristics, and management of RS in the East of Scotland (EoS) region. METHODS: Retrospective case note review of infants born in EoS from 2004 to 2013 with a clinical diagnosis of RS. Cases were identified by searching the regional cleft service patient database and review of Hospital Activity Statistics data. Regional live birth rate provided the denominator for incidence calculations. RESULTS: A total of 105 cases of RS were identified, giving a birth prevalence of 1:2685 live births. No trends in annual incidence were observed over the 10-year period. Intrauterine exposure to potentially teratogenic agents was identified in 17% cases, including Methadone in 8% cases. Signs of UAO were present in 93% of infants, 63% of whom required active airway management. Nasopharyngeal airway (NPA) was the most commonly used intervention (53% cases), whilst only 7% required surgical management. Infants with an underlying syndrome or additional anomalies (RS+) were significantly more likely to be admitted to a tertiary center and require surgical airway or feeding support compared to those with isolated RS. CONCLUSIONS: RS incidence in EoS is substantially higher than that reported within other populations, and than previously reported in the UK. A possible association with intrauterine Methadone exposure warrants further investigation.

Richieri-Costa-Pereira syndrome: Expanding its phenotypic and genotypic spectrum.

Richieri-Costa-Pereira syndrome is a rare autosomal recessive acrofacial dysostosis that has been mainly described in Brazilian individuals. The cardinal features include Robin sequence, cleft mandible, laryngeal anomalies and limb defects. A biallelic expansion of a complex repeated motif in the 5' untranslated region of EIF4A3 has been shown to cause this syndrome, commonly with 15 or 16 repeats. The only patient with mild clinical findings harbored a 14-repeat expansion in 1 allele and a point mutation in the other allele. This proband is described here in more details, as well as is his affected sister, and 5 new individuals with Richieri-Costa-Pereira syndrome, including a patient from England, of African ancestry. This study has expanded the phenotype in this syndrome by the observation of microcephaly, better characterization of skeletal abnormalities, less severe phenotype with only mild facial dysmorphisms and limb anomalies, as well as the absence of cleft mandible, which is a hallmark of the syndrome. Although the most frequent mutation in this study was the recurrent 16-repeat expansion in EIF4A3, there was an overrepresentation of the 14-repeat expansion, with mild phenotypic expression, thus suggesting that the number of these motifs could play a role in phenotypic delineation.

[Cleft lip and palate]. / Lippen-Kiefer-Gaumen-Spalten.

BACKGROUND: Cleft lip and palate (CLP) represents a group of malformations of unknown etiology but similar phenotypes. This implies consequences for the diagnostics, therapy, prevention, prognosis and risk estimation. OBJECTIVE: Definition of CLP subtypes and the embryonic development, clarification of correlations and differences between entities using epidemiological data, overview of the present state of genetic analyses, correlation to syndromes, sequences and associations and resulting consequences for clinical practice. MATERIAL AND METHODS: Update on embryological development of the face, summary of epidemiological and genetic studies and considerations on pedopathological and forensic aspects. RESULTS: Syndromic and non-syndromic CLP exhibit different and highly variable etiologies, therapeutic needs and prognosis. A thorough understanding is mandatory to distinguish between the different subgroups. In addition to specific aspects of CLP for the pediatric (forensic) pathologist this article provides an overall view of the topic which aims to help understand these malformations.

Health-related quality of life in children with Robin sequence.

This patient-reported outcome (PRO) study reports on 102 children with Robin sequence (RS) and their parents. There has been differentiated between those with isolated RS and those with RS as part of a syndrome, and take various treatments into account. All RS families from an earlier described cohort were invited to participate. Parents and RS children completed online questionnaires regarding health-related quality of life (HRQoL), satisfaction with appearance, parental distress, and RS specific topics. Results were compared with the Dutch norm population if available. There was no major difference in HRQoL in RS children and the Dutch norm population, nor between children with isolated RS and those with RS as part of a syndrome. The latter is likely due to the large percentage of children with Stickler syndrome, and small number of RS children with intellectual disability. Parental distress was higher in RS children with syndromes compared to parents of isolated RS children. When comparing various treatments, the subgroup treated by mandibular distraction showed a tendency of lower HRQoL scores, less satisfaction with appearance, and more parental distress. Also in the NPA group parents showed a tendency of more parental distress. Subgroups for each treatment were very small, however, and firm conclusions cannot be drawn. In this study, HRQoL in RS children is demonstrated comparable to the norm population, despite variations in treatment, possibly with less favorable outcome for children who received mandibular distraction. Markedly larger studies are needed to allow more reliable comparison of PROs in various treatments, and to incorporate PROs in management guidelines to obtain optimal patient care. © 2016 Wiley Periodicals, Inc.

[Neonatal treatment of stage 3 Pierre Robin sequence by mean of a naso-pharyngeal tube]. / Traitement néonatal par tube nasopharyngé dans les séquences de Pierre-Robin stade 3.

INTRODUCTION: In the stage 3 Pierre Robin sequence, glossoptosis is responsible for pharyngeal obstruction and for respiratory and eating disorders. An alternative to labioglossopexie, tracheotomy or mandibular distraction is the placing of a nasal pharyngeal tube in order to lift the lingual obstacle. MATERIAL AND METHOD: In our series of 15 new born with a stage 3 Pierre-Robin sequence, the nasal pharyngeal tube was positioned a few days after birth. RESULT: Ventilation and oxygen saturation were satisfactory. A lowering of hypercapnia and a rise of the weight curve were observed. The tube had to be maintained 64 days on average. No specific complication was noticed. DISCUSSION: The nasal pharyngeal tube lifts the lingual obstacle, improves hypercapnia and allows for a weight gain. In case of glossoptosis, hypercapnia may be ignored or underestimated. Normal oxygen saturation may be falsely reassuring while severe hypercapnia is occurring. Attentive care and parental involvement are needed.

Pierre Robin sequence: Management of respiratory and feeding complications during the first year of life in a tertiary referral centre.

OBJECTIVES: To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. METHODS: Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. RESULTS: Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p-values=0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. CONCLUSIONS: PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems.

Birth prevalence of Robin sequence in the Netherlands from 2000-2010: a retrospective population-based study in a large Dutch cohort and review of the literature.

The birth prevalence of Robin sequence (RS) is frequently cited to be 1 in 8,500 to 14,000 live births (range: 7,1-11,8 per 100.000), which is based on just a few epidemiological studies. The objective of this study is to contribute to the limited knowledge of the epidemiology of RS by determining the frequency of RS in a cleft palate (CP) population and the estimated birth prevalence in live births in the Netherlands, using distinct diagnostic criteria. A retrospective population-based analysis of the National Cleft Registry was performed in order to obtain all CP patients registered in the Netherlands from 2000-2010, in addition to a thorough review of the medical records in three Dutch Academic Pediatric Hospitals for the same period. Furthermore, a systematic search of the literature was conducted to allow for comparison of our findings. The Dutch birth prevalence of RS was estimated to be 1:5,600 live births (or 17.7 per 100,000), with a slight female predominance. RS was estimated to occur in a third of the CP population and patients with RS had a more severe cleft grade than the general CP population. The literature search yielded 42 studies reporting the birth prevalence for RS, which varied between 1:3,900 and 1:122,400 (0.8-32.0 per 100,000), with a mean prevalence of 1:24,500 (8.0 per 100,000). The birth prevalence of RS in the Netherlands was higher than reported for most other countries when similar diagnostic criteria were used, with a slight female predominance. A third of the general CP could be classified as RS.

Bilateral Hypodontia in Adolescents With Pierre Robin Sequence.

OBJECTIVE: To describe the frequency of hypodontia and left-right symmetry of hypodontia in the permanent dentition of children with Pierre Robin sequence (PRS). PATIENTS AND METHOD: The sample consisted of 78 children born with PRS between 1980 and 2006 and referred to the Oslo Cleft Lip and Palate Team (OCLPT). Data were collected retrospectively from the archives of the OCLPT. Panoramic radiographs were evaluated to document hypodontia; third molars were excluded. RESULTS: Of the 78 children with PRS, hypodontia was found in 33 (42%). Of the 33 children with hypodontia, 27 (82%) showed hypodontia in the micrognathic lower arch, 24 (73%) were missing two or more permanent teeth, and 2 (6%) had oligodontia. The teeth most often missing were the mandibular second premolar (72%), followed by the maxillar second premolar (29%). Most cases of hypodontia 21 (64%) occurred bilaterally. Bilateral hypodontia of the mandibular second premolar occurred in 27 (73%) of the patients. CONCLUSION: Hypodontia was found in 33 (42%) of the children with PRS, which is seven times higher than the prevalence among children without PRS (6%). Unlike in the general population, bilateral hypodontia was more common than unilateral hypodontia in the micrognathic mandible of children with PRS.