Intellectual Functioning of Children With Isolated PRS, PRS-Plus, and Syndromic PRS.

OBJECTIVE: Describe the intelligence quotient (IQ) of children with Pierre Robin sequence (PRS). DESIGN: Prospective cohort study. SETTING: Neurodevelopmental follow-up clinic within a hospital. PATIENTS: Children with PRS (n = 45) who had been in the Neonatal Intensive Care Unit (NICU) were classified by a geneticist into 3 subgroups of isolated PRS (n = 20), PRS-plus additional medical features (n = 8), and syndromic PRS (n = 17) based on medical record review and genetic testing. MAIN OUTCOME MEASURE: Children with PRS completed IQ testing at 5 or 8 years of age with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III) or Fourth Edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) or Fifth Edition (WISC-V). RESULTS: IQ scores were more than 1 to 2 standard deviations below the mean for 36% of the overall sample, which was significantly greater compared to test norms (binomial test P = .001). There was a significant association between PRS subtype and IQ (Fisher's exact P = .026). While only 20% of children with isolated PRS were within 1 standard deviation below average and 35% of children with syndromic PRS were below 1 to 2 standard deviations, 75% of PRS-plus children scored lower than 1 to 2 standard deviations below the mean. CONCLUSION: PRS subgroups can help identify children at risk for cognitive delay. The majority of children with PRS-plus had low intellectual functioning, in contrast to the third of children with syndromic PRS who had low IQ and the majority of children with isolated PRS who had average or higher IQ.

Rescue of Premature Coronal Suture Fusion with TGF-ß2 Neutralizing Antibody in Rabbits with Delayed-Onset Synostosis.

OBJECTIVES: An overexpression of Tgf-ß2 leads to calvarial hyperostosis and suture fusion in individuals with craniosynostosis. Inhibition of Tgf-ß2 may help rescue fusing sutures and restore normal growth. The present study was designed to test this hypothesis. DESIGN: Twenty-eight New Zealand White rabbits with delayed-onset coronal synostosis had radiopaque markers placed on either side of the coronal sutures at 10 days of age. The rabbits were randomly assigned to: (1) sham control rabbits (n = 10), (2) rabbits with control IgG (100 µg/suture) delivered in a collagen vehicle (n = 9), and (3) rabbits with Tgf-ß2 neutralizing antibody (100 µg/suture) delivered in a collagen vehicle (n = 9). Longitudinal growth data were collected at 10, 25, 42, and 84 days of age. Sutures were harvested at 84 days of age for histomorphometry. RESULTS: Radiographic analysis showed significantly greater ( P < .05) coronal suture marker separation, craniofacial length, cranial vault length, height, shape indices, cranial base length, and more lordotic cranial base angles in rabbits treated with anti-Tgf-ß2 antibody than in controls at 42 and 84 days of age. Histologically, rabbits treated with anti-Tgf-ß2 antibody at 84 days of age had patent and significantly ( P < .05) wider coronal sutures and greater sutural area compared to controls. CONCLUSIONS: These data support our hypothesis that antagonism of Tgf-ß2 may rescue fusing coronal sutures and facilitate craniofacial growth in this rabbit model. These findings also suggest that cytokine therapy may have clinical significance in infants with progressive postgestational craniosynostosis.

Infant Mandibular Distraction for Upper Airway Obstruction: A Clinical Audit.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is an effective method of treating upper airway obstruction (UAO) in micrognathic infants. The short-term outcomes include relief of UAO, avoidance of tracheostomy, and prompt discharge from hospital. However, it is a significant surgical procedure with potential associated morbidities. This study describes a cohort of infants managed using MDO over a twelve-year period. METHODS: A retrospective chart review was undertaken for children who had MDO before the age of 5 years between 2000 and 2012. This was followed by a clinical review of the same cohort specifically looking for dental anomalies, nerve injuries, and scar cosmesis. RESULTS: Seventy-three children underwent MDO at a mean age of 2 months [interquartile range (IQR), 1.7-4.2] for nonsyndromic infants and 3.3 months (IQR, 2.1-7.4) for those with syndromes. Infants were discharged from hospital, on average, 15 days after procedure. After MDO, of the 9 who were previously tracheostomy dependent, 5 (56%) were decannulated within 12 months and none of the nontracheostomy-dependent children required further airway assistance. The majority of children required supplemental feeding preoperatively but, 12 months postoperatively, 97% of the nonsyndromic infants fed orally. Thirty-nine children (53%) were reviewed clinically [median age, 5.1 y (IQR, 3.9-6.5)] with 18 being syndromic. Many of the mandibular first permanent and second primary molars had developmental defects, but there was a low rate of neurosensory deficit and good scar cosmesis. CONCLUSIONS: This study contributes further to the evidence base underpinning the management of micrognathic infants with UAO.

The role of distraction osteogenesis in the management of craniofacial syndromes.

Distraction osteogenesis (DO) has been established as a useful technique in the correction of skeletal anomalies of the long bones for several decades. However, the use of DO in the management of craniofacial deformities has been evolving over the past 20 years, with initial experience in the mandible, followed by the mid-face and subsequently, the cranium. This review aims to provide an overview of the current role of DO in the treatment of patients with craniofacial anomalies.

Anesthetic implications of infants with mandibular hypoplasia treated with mandibular distraction osteogenesis.

OBJECTIVES: To document the incidence of difficult intubation following mandibular distraction osteogenesis (MDO) in children with severe mandibular hypoplasia. BACKGROUND: Syndromes associated with significant mandibular hypoplasia, especially Pierre Robin sequence, provide a challenge in airway management both in and out of the operating room. Mandibular advancement using mandibular distraction osteogenesis devices has been used in infants in an attempt to reduce the incidence of acute life-threatening airway obstruction. Whether MDO also reduces the incidence of difficult intubation has not been adequately described. METHODS: A retrospective chart review of 51 infants with upper airway obstruction secondary to mandibular hypoplasia who required MDO between January 2002 and 2012. The primary outcome was the incidence of difficult or failed intubation. Secondary outcomes were the relationship between syndrome type and the incidence of difficult intubation. RESULTS: Fifty-one PRS infants were identified. Twenty-eight patients had isolated PRS, six had syndromic PRS, seven had Treacher Collins syndrome, and 10 had another coexisting syndrome. Prior to mandibular distraction osteogenesis (MDO), the incidence of difficult intubation was 71%, with the highest incidence in patients with Treacher Collins syndrome (100%), sPRS syndrome (100%), and PRS (65%). Following MDO, the incidence of difficult intubation was 8.3%. The difference was statistically significant for all patients (Kruskal-Wallis rank test P = 0.0001) those with isolated PRS (P = 0.0001), syndromic PRS (P = 0.0023), and other syndromes (P = 0.0002), but not for Treacher Collins syndrome (P = 0.21). Three patients had pre existing tracheostomies. CONCLUSIONS: In a select group of infants with severe upper airway obstruction who have failed nonsurgical airway interventions, mandibular distraction osteogenesis reduces the incidence of difficult mask ventilation and difficult intubation. We were not able to compare the improvement in airway management to a comparable group of PRS infants who did not undergo surgical intervention. The improvement in laryngeal view was most marked for infants with isolated PRS but no significant benefit was demonstrated in infants with TCS.

Growth and development considerations for craniomaxillofacial surgery.

The purpose of craniomaxillofacial surgery is to improve function, occlusion, craniofacial balance, and aesthetics. Accurate diagnosis, assessment, and careful treatment planning are essential in achieving a successful outcome, and an understanding of the pattern of facial growth is integral in this process. Patients with craniofacial congenital dysmorphologies, posttraumatic asymmetries, or disturbances of facial balance from radiation may have functional and/or aesthetic issues that require treatment. Understanding the complexities of growth in the skull and face is a key component to appropriate treatment planning for these disorders. This article reviews growth and development in the craniofacial skeleton.

Repair of critical size defects in the rabbit calvarium with the use of a novel scaffold material.

A number of materials have been implanted into skull defects to determine if improved healing outcomes can be achieved. In some instances, packing or implanting bone-inducing alloplasts into a standardized skull defect results in better healing than an untreated defect. AlloDerm is a skin derived acellular collagen membrane and has characteristics that are known to be effective in promoting bone growth. It has not been previously investigated for use in cranial bone healing. The aim of the investigation was to determine if implanting this novel scaffold into skull defects will improve the quality of bone repair. Six rabbits received AlloDerm grafts into critical-sized calvarial defects. The rabbits were sacrificed at two months and the specimens examined histologically and radiographically. At the time of sacrifice, it was found that while bony growth had commenced at the margins of the defect and as isolated islands within the graft, there did not appear to be a major benefit in using the material described.

Postoperative anti-Tgf-beta2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits.

Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-beta2 (Tgf-beta2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-beta2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n=9); 2) suturectomy with nonspecific, control IgG antibody (n=9); and 3) suturectomy with anti-Tgf-beta2 antibody (n=11). At 10 days of age, a 3 mm x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 microg/suture) or anti-Tgf-beta2 (100 microg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P<0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. Cephalometric analysis revealed significant (P<0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. These data support the initial hypothesis that interference with Tgf-beta2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

Cysts of the jaws and advances in the diagnosis and management of nevoid Basal cell carcinoma syndrome.

Cysts of the jaws are a relatively commonly encountered pathologic condition, and a full spectrum of these lesions may present in pediatric patients. Most cystic lesions are of odontogenic origin, as seen in adult patients, and a range of surgical approaches are available for their management. These approaches are based on the clinical and radiologic features and the behavioral and histologic characteristics of each cyst. Advances in imaging techniques and laboratory investigations, such as immunocytochemistry and genetic analysis, will continue to facilitate improved diagnoses, patient management, and clinical outcomes.

The role of distraction osteogenesis in the management of craniofacial syndromes.

In patients with craniofacial syndromes, the skeletal discrepancy is often severe, and the ability to achieve the desired movement by immediate surgical repositioning is difficult because of restrictions of the soft-tissue envelope. The technique of distraction osteogenesis has provided an additional option for managing congenital and acquired craniofacial deformities. The use of distraction osteogenesis is, however, still within its infancy as a treatment modality. It is unlikely that the procedure will obviate the need for definitive orthognathic surgery at skeletal maturity in most patients with craniofacial anomalies. The role of distraction osteogenesis in craniofacial surgery will continue to evolve rapidly with increasing experience and technological advancement. Because distraction osteogenesis in the facial skeleton is a relatively new approach, analysis of the contemporary literature is imperative, and future long-term studies on the effects and outcome of distraction are essential.

A comparison of the stability of single-piece and segmental Le Fort I maxillary advancements.

This study retrospectively evaluated the stability of Le Fort I maxillary advancements and compared segmental and one-piece maxillary osteotomy procedures. A cephalometric analysis was performed on 26 cases of maxillary advancement. The sample comprised 11 cases of one-piece and 15 cases of segmental maxillary procedures. The tracings were superimposed and digitized by computer software, and the skeletal changes were analyzed before surgery, immediately after surgery, and at a minimum of 1 year of follow-up. Different values were compared by the paired and nonpaired t tests and were correlated by the Pearson correlation test. The significant value was set at a 95% confidence interval. The maxilla was advanced by a mean of 5.0 +/- 1.6 mm (P < 0.001), and the anterior maxilla was repositioned inferiorly by a mean of 1.5 +/- 3.3 mm (P < 0.05). The maxilla relapsed posteriorly by a mean of 0.6 +/- 1.2 mm (P < 0.05) and superiorly at the anterior maxilla by a mean of 0.8 +/- 1.1 mm (P < 0.001). Overjet and overbite did not significantly change (P > 0.05). It was concluded that maxillary advancement using rigid fixation and interpositional bone grafting in both groups was a stable procedure, particularly in the horizontal plane. In the one-piece group, there was a significantly higher relapse in the vertical plane than in the segmental group (P < 0.05), however. Minor skeletal relapse was compensated for by postoperative tooth movement, and segmental procedures are recommended when required to enhance occlusal results.

Stability of combined Le Fort I maxillary advancement and mandibular reduction.

BACKGROUND: There have been reports that correction of severe Class III abnormality by single jaw surgery may invite relapse in the long-term. The purpose of this study was to retrospectively evaluate the stability of combined Le Fort I maxillary advancement and bilateral sagittal split osteotomies for mandibular reduction. METHODS: Thirty patients with a skeletal Class III malocclusion underwent bimaxillary surgery using rigid fixation and interpositional bone grafting of the maxilla. The average age was 24.4 years, and the mean follow-up period was 20 months (Range: 12-63 months). Post-operative changes were measured on lateral cephalometric radiographs using an anatomical best-fit technique. RESULTS: The maxilla was advanced, on average, 6.1 mm (SD: 1.8 mm) and repositioned superiorly at PNS 1.9 mm (SD: 2.1 mm). The mandible was repositioned posteriorly 5.6 mm ISD: 4.2 mm) at menton, which also auto-rotated superiorly. At follow-up, the maxilla relapsed horizontally 0.6 mm (SD: 1.1 mm, p < 0.01) with no significant vertical change. The maxillary central incisors were proclined and the interincisal angle was reduced. Menton relapsed anteriorly 1.4 mm (SD: 2.7 mm, p < 0.01), and gonion rotated superiorly 1.5 mm (SD: 2.3 mm, p < 0.001). In 67 per cent of cases menton moved anteriorly less than 2.5 mm. The overjet and overbite did not change significantly. CONCLUSIONS: The data show that 12-months post-operatively, maxillary advancement combined with mandibular setback was relatively stable in the horizontal and vertical planes.