Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence.

Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high-volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U-shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U-shaped CP. The most common palatal morphology among those who died was an intact palate. U-shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.

Predictors of Failure in Infant Mandibular Distraction Osteogenesis.

PURPOSE: Mandibular distraction osteogenesis (MDO) has been shown to be successful in treating upper airway obstruction caused by micrognathia in pediatric patients. The purpose of this study was to assess the success rate of MDO and possible predictors of failure. PATIENTS AND METHODS: The records of all neonates and infants who underwent MDO from 2008 to 2015 were retrospectively reviewed. Procedural failure was defined as patient death or the need for tracheostomy postoperatively. Details of distraction, length of stay, and failures were captured and elucidated. RESULTS: Of the 82 patients, 47 (57.3%) were male; 46 (56.1%) had sporadic Pierre Robin sequence; 33 (40.3%) had syndromic Pierre Robin sequence; and 3 (3.7%) had micrognathia, not otherwise specified. The average distraction length was 27.5 mm (range, 15 to 30 mm; SD, 4.4 mm), the average age at operation was 63.3 days (range, 3 to 342 days; SD, 71.4 days), and the average length of post-MDO hospital stay was 43 days (range, 9 to 219 days; SD, 35 days) with an average follow-up period of 4.3 years (range, 1.1 to 9.6 years; SD, 2.6 years). There were 7 failures (8.5%) (5 tracheostomies and 2 deaths) resulting in a 91.5% success rate. Regression analysis showed that the predicted probability of the need for tracheostomy was 45% (P = .02) when the patient had a central nervous system (CNS) anomaly. The predicted probability of the need for tracheostomy and death combined was 99.6% when the patient had laryngomalacia and a CNS anomaly and was preoperatively intubated (P < .05). CONCLUSIONS: This review confirms that MDO is an effective method of treating the upper airway obstruction caused by micrognathia with a high success rate. In our sample the presence of CNS abnormalities, laryngomalacia, and preoperative intubation had a significant impact on the failure rate.

Mortality in Robin sequence: identification of risk factors.

Although Robin sequence (RS) is a well-known phenomenon, it is still associated with considerable morbidity and even mortality. The purposes of this study were to gain greater insight into the mortality rate and identify risk factors associated with mortality in RS. We retrospectively reviewed all RS infants followed at the Wilhelmina Children's Hospital from 1995 to 2016. Outcome measurements were death and causes of death. The authors identified 103 consecutive RS infants with a median follow-up of 8.6 years (range 0.1-21.9 years). Ten of the 103 infants (10%) died at a median age of 0.8 years (range 0.1-5.9 years). Nine of these ten infants (90%) were diagnosed with an associated syndrome. Of these, seven infants died of respiratory insufficiency due to various causes (two related to upper airway obstruction). The other two syndromic RS infants died of arrhythmia due to hypernatremia and of West syndrome with status epilepticus. One isolated RS infant died of brain ischemia after MDO surgery. Cardiac anomalies were observed in 41% and neurological anomalies in 36%. The presence of a neurological anomaly was associated with a mortality rate of 40% versus 7% in infants with no neurological anomaly (p = 0.016), with an odds ratio of 8.3 (95% CI 1.4-49.0) for neurological anomaly versus no neurological anomaly. Mortality was 15% in infants with syndromic RS versus 2% in infants with isolated RS (p = 0.044). Mortality was not significantly associated with the presence of a cardiac anomaly, surgical treatment for severe respiratory distress in the neonatal period, or prematurity. CONCLUSION: RS represents a heterogeneous patient population and is associated with a high level of underlying syndromes. The present study reports a mortality rate of 10% significantly associated with syndromic RS and the presence of neurological anomalies. A multidisciplinary approach in all infants born with RS, including genetic testing and examination of neurological anomalies in a standardized way, is crucial to identify infants with underlying syndromes potentially associated with increased mortality. What is Known: • Reported mortality rates in Robin sequence vary from 2% to 26%. • Clinicians mainly focus on the morbidity of Robin sequence that includes respiratory complications due to upper airway obstruction in the period after birth. • Robin sequence represents a heterogeneous patient population and is associated with a high level of underlying syndromes. What is New: • The present study reports a mortality rate of 10% significantly associated with syndromic Robin sequence and the presence of neurological anomalies. • A multidisciplinary approach in all infants born with Robin sequence, including genetic evaluation and standardized workup for neurological anomalies, is crucial to identify infants with underlying syndromes potentially associated with increased mortality.

Outcome Following Surgical Interventions for Micrognathia in Infants With Pierre Robin Sequence: A Systematic Review of the Literature.

BACKGROUND: Tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and subperiosteal release of the floor of the mouth (SPRFM) are the most commonly performed surgical procedures to treat severe airway obstruction in infants born with Pierre Robin sequence (PRS). OBJECTIVES: To determine the rate of failure of each type of procedure, in terms of mortality and the need for tracheostomy, and to determine what proportion of infants have significant airway obstruction postoperatively as determined by polysomnography (PSG) and compare the data by procedure type. METHOD: A comprehensive literature search (1981 through June 2015) was done of the National Library of Medicine database using PubMed. Extracted data included diagnosis, type of surgery, and outcome including mortality, need for postoperative tracheostomy and details of PSG. Persistence of significant airway obstruction was defined as an apnea-hypopnea index >15 events/h on PSG. RESULTS: Both mortality rate and need for tracheostomy were low for all procedures. Many studies lacked sufficient detail to identify significant airway obstruction postoperatively. In studies with sufficient data, MDO was associated with the lowest percentage of significant airway obstruction postprocedure (3.6%) compared to 50% for infants who underwent TLA. Insufficient PSG data was available for patients who were treated with SPRFM. CONCLUSIONS: There is a paucity of objective PSG data to definitively assess postoperative airway outcomes for PRS. MDO appears to be the most effective technique based on the available PSG data. Standardized use of PSG may lead to better identification and treatment of patients at risk for suboptimal airway outcomes postoperatively.

In Situ and Home Care Nasopharyngeal Intubation Improves Respiratory Condition and Prevents Surgical Procedures in Early Infancy of Severe Cases of Robin Sequence.

AIM: To evaluate the clinical outcome of infants with Robin Sequence (RS) and severe respiratory obstruction managed with nasopharyngeal intubation (NPI). METHODS: This prospective study was conducted with 107 infants with RS admitted to the Hospital for Craniofacial Anomalies of the University of São Paulo (HRAC-USP), from July 2003 to June 2010, diagnosed with severe RS and treated with NPI. The infants were followed up for the first year of life. Clinical findings, morbidity, and mortality were recorded. RESULTS: Of the 223 infants with RS admitted to the hospital in the period studied, 149 were diagnosed with severe respiratory distress and 107 (71.81%) matched all the inclusion criteria. Of those, 78 (73%) presented Isolated Robin Sequence and 29 (27%) presented other syndromes or anomalies associated with RS. NPI treatment lasted an average of 57 days and the mean hospitalization time was 18 days. Although all infants presented feeding difficulties, 85% were fed orally and only 15% underwent gastrostomy. Morbidity was 14% and no deaths occurred. CONCLUSIONS: The children treated with the RS treatment protocol adopted at the HRAC-USP had improved respiratory and feeding difficulties, required a shorter hospitalization time, and presented low morbidity and mortality during the first year of life. The general outcome prevented surgical procedures in early infancy.

Robin sequence: mortality, causes of death, and clinical outcomes.

BACKGROUND: The authors report the cause of and risk factors for mortality in infants with Robin sequence and identify characteristics associated with quality-of-life outcomes. METHODS: The authors performed an 11-year retrospective review of all infants with Robin sequence treated at a neonatal intensive care unit. Patient characteristics were correlated to mortality and quality-of-life measures. Emergency room visits and hospital admissions were used to assess quality-of-life outcomes. Significant variables were identified by means of univariate analysis. RESULTS: One hundred eighty-one consecutive infants were identified. Patient characteristics included the following: isolated, 32.6 percent; syndromic, 31.5 percent; gastrointestinal, 38.1 percent; pulmonary, 32.6 percent; cardiac, 30.9 percent; central nervous system, 25.4 percent; and two or more organ system anomalies, 69.6 percent. Mortality was 16.6 percent; two deaths were related to airway obstruction problems. There were no deaths in isolated Robin sequence (p = 0.002). Mortality was statistically associated with cardiac anomalies (p < 0.001), central nervous system anomalies (p = 0.001), and two or more organ system abnormalities (p = 0.001). Variables associated with an increased rate of emergency room visits were cardiac anomalies (p = 0.04) and two or more organ system abnormalities (p = 0.04). The presence of two or more organ system abnormalities (p = 0.04) was associated with an increased hospital admission rate. CONCLUSIONS: Mortality and negative quality-of-life measures in Robin sequence are not directly related to respiratory obstruction. Isolated Robin sequence confers no increased risk of mortality. There is a high incidence of cardiac and central nervous system anomalies, which are significantly associated with mortality. Cardiac and cranial imaging should be performed during the initial evaluation of infants with Robin sequence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Long-term survival in TARP syndrome and confirmation of RBM10 as the disease-causing gene.

TARP syndrome, comprising Talipes equinovarus, atrial septal defect (ASD), Robin sequence (micrognathia, glossoptosis, and cleft palate), and persistence of the left superior vena cava, is an X-linked condition with pre- or postnatal lethality in affected males. Based on linkage studies and massively parallel sequencing of X-chromosome exons in two families, the disease-causing gene was identified as RBM10. We identified a maternally inherited frameshift mutation in an unrelated patient, confirming RBM10 as the disease gene. This is the first reported individual with TARP syndrome who survived past early infancy, thus expanding the phenotypic spectrum of this disorder. In addition to the characteristic cleft palate, ASD, and persistent superior vena cava, he had low-set and posteriorly angulated ears, upslanting palpebral fissures, cryptorchidism, and structural brain abnormalities including partial agenesis of the corpus callosum, dysplastic enlarged caudate, and cerebellar hypoplasia with megacisterna magna. Preterm delivery, suspected pulmonary hypoplasia, and pulmonary hypertension resulted in chronic lung disease. At the age of 3(7)/(12) years, he remained ventilator-dependent at night, and he was fed exclusively through a gastro-jejunal tube. Sensorineural hearing loss required a hearing aid. Optic atrophy and cortical visual impairment were noted. He was unable to sit independently, was non-communicative and he had severe intellectual disability. Atrial flutter required recurrent ablation of intra-atrial re-entry pathways. The mother's heterozygosity for the RBM10 mutation underscored the importance of accurate diagnosis and counseling for TARP syndrome.

Pierre Robin sequence: a series of 117 consecutive cases.

A series of 117 cases of Pierre Robin Sequence are classified as isolated (48%), syndromic (35%), and with associated anomalies (17%); the latter group had a poor long-term prognosis. In isolated Pierre Robin Sequence, familial cases and a high incidence of twins were noted. Among syndromic Pierre Robin Sequence, 4 syndromes represent more than 50% of the diagnoses.

The Pierre Robin sequence: review of 125 cases and evolution of treatment modalities.

All children admitted to our hospital between 1964 and 1991 with a diagnosis of Pierre Robin sequence were divided into three groups according to the severity of their symptoms: group I: adequate respiration in prone position and bottle feeding; group II: adequate respiration in prone position but feeding difficulties requiring gavage; and group III: children with respiratory distress and endotracheal intubation and gavage. The presence of associated anomalies, prematurity, and psychomotor impairment was noted as well as the surgical interventions performed. We found 56 children (44.8 percent) in group I, 40 children (32 percent) in group II, and 29 children (23.2 percent) in group III. Seventeen children (13.6 percent) died: 1 of 56 in group I, 4 of 40 in group II, and 12 of 29 in group III. Among the 125 patients, 57 presented at least one associated anomaly other than a cleft palate and the Pierre Robin triad. Thirteen deaths were found in this group (13 of 57 = 22.8 percent). Ten children were premature (10 of 125), and 6 of the premature infants died (60 percent). Twenty-two children required at least one surgical procedure to relieve the upper airway obstruction. Among the 108 survivors in this study, 25 presented a psychomotor impairment (23.1 percent). The children admitted after 1986 were submitted to routine serial blood gases, oxygen saturation monitoring, and polysomnographic recordings. The therapeutic interventions were done earlier. Thirty-four children were followed after 1986: 14 in group I, 11 in group II, and 9 in group III.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cerebro-costo-mandibular syndrome (author's transl)]. / Le syndrome cérébro-costo-mandibulaire.

This rare condition associates a Pierre Robin syndrome with costal and intellectual abnormalities. It usually rapidly results in death from pulmonary complications.