Nonsyndromic cleft lip and palate: CRISPLD genes and the folate gene pathway connection.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect that has a multifactorial etiology. Despite having substantial genetic liability, <15% of the genetic contribution to NSCLP has been delineated. In our efforts to dissect the genetics of NSCLP, we found that variation in the CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) gene is associated with NSCLP and that the protein is expressed in the developing murine craniofacies. In addition, we found suggestive linkage of NSCLP (LOD > 1.0) to the chromosomal region on 8q13.2-21.13 that contains the CRISPLD1 gene. The protein products of both CRISPLD1 and CRISPLD2 contain more cysteine residues than comparably sized proteins. Interestingly, the folic acid pathway produces endogenous cysteines, and variation in genes in this pathway is associated with NSCLP. Based on these observations, we hypothesized that variation in CRISPLD1 contributes to NSCLP and that both CRISPLD genes interact with each other and genes in the folic acid pathway. METHODS: Single nucleotide polymorphisms (SNPs) in CRISPLD1 were genotyped in our non-Hispanic white and Hispanic multiplex and simplex NSCLP families. RESULTS: There was little evidence for a role of variation for CRISPLD1 alone in NSCLP. However, interactions were detected between CRISPLD1/CRISPLD2 SNPs and variation in folate pathway genes. Altered transmission of one CRISPLD1 SNP was detected in the NHW simplex families. Importantly, interactions were detected between SNPs in CRISPLD1 and CRISPLD2 (15 interactions, 0.0031 ≤p < 0.05). CONCLUSION: These novel findings suggest that CRISPLD1 plays a role in NSCLP through the interaction with CRISPLD2 and folate pathway genes.

Folate pathway and nonsyndromic cleft lip and palate.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth defect. Periconceptional supplementation with folic acid, a key component in DNA synthesis and cell division, has reduced the birth prevalence of neural tube defects and may similarly reduce the birth prevalence of other complex birth defects including NSCLP. Past studies investigating the role of two common methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs), C677T (rs1801133) and A1298C (rs1801131), in NSCLP have produced conflicting results. Most studies of folate pathway genes have been limited in scope, as few genes/SNPs have been interrogated. Here, we asked whether variations in a more comprehensive group of folate pathway genes were associated with NSCLP, and were there detectable interactions between these genes and environmental exposures? METHODS: Fourteen folate metabolism-related genes were interrogated using 89 SNPs in multiplex and simplex non-Hispanic white and Hispanic NSCLP families. RESULTS: Evidence for a risk association between NSCLP and SNPs in NOS3 and TYMS was detected in the non-Hispanic white group, whereas associations with MTR, BHMT2, MTHFS, and SLC19A1 were detected in the Hispanic group. Evidence for over-transmission of haplotypes and gene interactions in the methionine arm was detected. CONCLUSIONS: These results suggest that perturbations of the genes in the folate pathway may contribute to NSCLP. There was evidence for an interaction between several SNPs and maternal smoking, and for one SNP with gender of the offspring. These results provide support for other studies that suggest that high maternal homocysteine levels may contribute to NSCLP and should be further investigated.

General management considerations in pediatric facial fractures.

The treatment of pediatric facial fractures, although similar to that of adults, requires a separate and thorough understanding of the unique developmental issues inherent to this age group. The contribution of several of these factors allows for a large portion of these injuries to be managed more conservatively; however, operative indications still exist. The optimal form of management in these situations must balance the risks of impacting dentition or future skeletal growth versus obtaining acceptable stability and reduction for healing. Although these principles have remained largely unchanged over the years, a more current discussion on the state of resorbable and titanium fixation is offered to highlight evolving management considerations. Although uniquely challenging, the proper management of pediatric facial trauma is possible if the treating physician remains aware of key anatomic, epidemiological, evaluation, and management issues.

A novel autologous scaffold for diced-cartilage grafts in dorsal augmentation rhinoplasty.

BACKGROUND: Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. METHODS: In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). RESULTS: A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. CONCLUSION: The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.

Packing and postoperative rhinoplasty management: a survey report.

BACKGROUND: Postoperative management following rhinoplasty varies greatly among aesthetic surgeons. Few studies have addressed practice trends in postoperative rhinoplasty care or questioned the frequency of packing and splinting. Many conventional postoperative techniques remain controversial (eg, packing). OBJECTIVE: To investigate current postoperative practices in the United States, correlating the results with surgical education, practice type, and complication rates. METHODS: An online survey was distributed to members of the American Society for Aesthetic Plastic Surgery. Respondents were polled about their background, route of education, type of practice, frequency and preference of postoperative nasal care, and most frequent rhinoplasty complications. Statistical analysis was performed with the χ(2) test. RESULTS: Of the 1550 total surveys sent, 126 responses were received (8.1%). The majority of respondents were in private practice (86%) and trained in plastic surgery (83%). Approximately 33% continue to regularly employ packing following rhinoplasty, but data show that surgeons performing 21 or more rhinoplasties per year were less likely to utilize packing (P = .06). Those surgeons with higher rhinoplasty case volumes were significantly more likely to utilize a secondary therapy (eg, steroids, arnica) in combination with ice packs (P = .03) to prevent postoperative ecchymosis. Finally, surgeons with lower rhinoplasty case volumes reported more frequent postoperative nasal tip deformities (P = .01). CONCLUSIONS: Postoperative rhinoplasty care varies greatly among practicing aesthetic surgeons. Importantly, a high percentage of private practice aesthetic surgeons continue to utilize nasal packing following rhinoplasty. However, these numbers trend downward in surgeons who perform rhinoplasties more frequently.

Perioperative steroids for minimizing edema and ecchymosis after rhinoplasty: a meta-analysis.

BACKGROUND: Minimizing complications after rhinoplasty is a priority for every surgeon performing the procedure. Perioperative steroid administration has been shown to decrease postoperative edema and ecchymosis in a number of prospective randomized trials. OBJECTIVES: In an effort to further elucidate the significance of the data and develop an evidence-based algorithm for steroid administration, the authors offer a meta-analysis of the existing literature. METHODS: A systematic review of the literature was performed. All articles were reviewed for relevant data, which were extracted, pooled, and compared. Seven prospective randomized trials investigating perioperative steroid use in rhinoplasty have been conducted and reported. Four of these studies had the same method of patient edema and ecchymosis assessment, and their data were compared. RESULTS: Based on results from the four relevant studies, perioperative steroid use significantly reduces postoperative edema and ecchymosis of the upper and lower eyelids at one day and seven days postoperatively (P < .0001). Preoperative steroid administration decreases postoperative upper and lower eyelid edema at one day preoperatively, when compared to postoperative administration (P < .05). Extended dosing is superior to one-time dosing (P < .05). CONCLUSIONS: Perioperative steroid use decreases postoperative edema and ecchymosis associated with rhinoplasty. Preoperative administration is superior to postoperative, and extended dosing is superior to singular. Based on these results, evidence-based guidelines for perioperative steroid administration can be given.

Variation in WNT genes is associated with non-syndromic cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect. Genetic and environmental factors have been causally implicated and studies have begun to delineate genetic contributions. The Wnt genes are involved in regulating mid-face development and upper lip fusion and are therefore strong candidates for an etiological role in NSCLP. Furthermore, the clf1 region in A/WyN clefting susceptible mice contains the Wnt3 and Wnt9B genes. To assess the role of the Wnt family of genes in NSCLP, we interrogated seven Wnt genes (Wnt3, Wnt3A, Wnt5A, Wnt7A, Wnt8A, Wnt9B and Wnt11) in our well-defined NSCLP dataset. Thirty-eight single nucleotide polymorphisms were genotyped in 132 multiplex NSCLP families and 354 simplex parent-child trios. In the entire dataset, single-nucleotide polymorphisms (SNPs) in three genes, Wnt3A (P = 0.006), Wnt 5A (P = 0.002) and Wnt11 (P = 0.0001) were significantly associated with NSCLP after correction for multiple testing. When stratified by ethnicity, the strongest associations were found for SNPs in Wnt3A (P = 0.0007), Wnt11 (P = 0.0012) and Wnt8A (P = 0.0013). Multiple haplotypes in Wnt genes were associated with NSCLP, and gene-gene interactions were observed between Wnt3A and both Wnt3 and Wnt5A (P = 0.004 and P = 0.039, respectively). This data suggests that alteration in Wnt gene function may perturb formation and/or fusion of the facial processes and predispose to NSCLP.

Family-based study shows heterogeneity of a susceptibility locus on chromosome 8q24 for nonsyndromic cleft lip and palate.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate is a common birth defect. Although a number of susceptibility loci have been reported, replication has often been lacking. This is likely due, in part, to the heterogeneity of datasets and methodologies. Two independent genome-wide association studies of individuals of largely western European extraction have identified a possible susceptibility locus on 8q24.21. METHODS: To determine the overall effect of this locus, we genotyped six of the previously associated single nucleotide polymorphisms in our Hispanic and non-Hispanic white family-based datasets and evaluated them for linkage and association. In addition, we genotyped a large African American family with nonsyndromic cleft lip with or without cleft palate that we had previously mapped to the 8q21.3-24.12 region to test for linkage. RESULTS: There was no evidence for linkage to this region in any of the three ethnic groups. Nevertheless, strong evidence for association was noted in the non-Hispanic white group, whereas none was detected in the Hispanic dataset. CONCLUSION: These results confirm the previously reported association and provide evidence suggesting that there is ethnically based heterogeneity for this locus.

Facial trauma: general principles of management.

Facial fractures are common problems encountered by the plastic surgeon. Although ubiquitous in nature, their optimal treatment requires precise knowledge of the most recent evidence-based and technologically advanced recommendations. This article discusses a variety of contemporary issues regarding facial fractures, including physical and radiologic diagnosis, treatment pearls and caveats, and the role of various synthetic materials and plating technologies for optimal facial fracture fixation.

Ethnic heterogeneity of IRF6 AP-2a binding site promoter SNP association with nonsyndromic cleft lip and palate.

OBJECTIVE: The goal of this study was to confirm the reported association between a noncoding SNP (rs642961) in IRF6 and nonsyndromic cleft lip and palate. DESIGN, SETTING, AND PARTICIPANTS: Two SNPs in IRF6 (rs2235371 and rs64296) were genotyped in Hispanic and non-Hispanic white multiplex (122) and simplex (308) nonsyndromic cleft lip and palate families. Linkage and family-based association analyses were performed on the individual SNPs as well as the 2-SNP haplotype. RESULTS: Only modest evidence was found for an association with rs642961 and the 2-SNP haplotype. In contrast, strong evidence was found for the association with rs2235371; this was most evident in the non-Hispanic white simplex families. CONCLUSIONS: Although it is confirmed that variation in IRF6 is associated with nonsyndromic cleft lip and palate, the results do not support the reported association with SNP rs64296. Importantly, the association varies between ethnic groups. This finding underscores the need for evaluating additional variations in IRF6 across multiple populations to better determine its role in nonsyndromic cleft lip and palate.

Contemporary techniques in inferior turbinate reduction: survey results of the American Society for Aesthetic Plastic Surgery.

BACKGROUND: Nasal airway obstruction is a frequently-encountered problem, often secondary to inferior turbinate hypertrophy. Medical treatment can be beneficial but is inadequate for many individuals. For these refractory cases, surgical intervention plays a key role in management. OBJECTIVE: The authors evaluate the current trends in surgical management of inferior turbinate hypertrophy and review the senior author's (SS) preferred technique. METHODS: A questionnaire was devised and sent to members of the American Society for Aesthetic Plastic Surgery (ASAPS) to determine their preferred methods for assessment and treatment of inferior turbinate hypertrophy. RESULTS: One hundred and twenty-seven physicians responded to the survey, with 85% of surveys completed fully. Of the responses, 117 (92%) respondents were trained solely in plastic surgery and 108 (86.4%) were in private practice. Roughly 81.6% of respondents employ a clinical exam alone to evaluate for airway issues. The most commonly-preferred techniques to treat inferior turbinate hypertrophy were a limited turbinate excision (61.9%) and turbinate outfracture (35.2%). CONCLUSIONS: Based on the results of this study, it appears that limited turbinate excision and turbinate outfracture are the most commonly-used techniques in private practice by plastic surgeons. Newer techniques such as radiofrequency coblation have yet to become prevalent in terms of application, despite their current prevalence within the medical literature. The optimal method of management for inferior turbinate reduction should take into consideration the surgeon's skill and preference, access to surgical instruments, mode of anesthesia, and the current literature.

Two hundred twenty-two consecutive pharyngeal flaps: an analysis of postoperative complications.

PURPOSE: The most frequent surgical technique used to treat velopharyngeal insufficiency (VPI), the pharyngeal flap is also one of the more dangerous pediatric procedures due to the potential for airway obstruction and patient death. Prompted by recent concerns over high complication rates associated with this procedure, we completed a retrospective cohort study to evaluate the incidence and character of postoperative complications after 222 consecutive pharyngeal flap surgeries. MATERIALS AND METHODS: A database review was undertaken of all pharyngeal flap surgeries completed from January 2000 to April 2006 at a tertiary pediatric craniofacial center. Main outcome measures included postoperative complications, such as airway compromise manifested as oxygen desaturation, hemorrhage requiring reoperation, wound infection, pharyngeal flap breakdown, and development of obstructive sleep apnea. RESULTS: In 222 consecutive pharyngeal flap patients, the mean age at surgery was 6.4 years (range, 3.1 to 17 years). Postoperative complications were rare in this cohort. Twelve patients (8.0%) required supplemental oxygenation for limited desaturation, and 3 patients (1.35%) demonstrated significant postoperative bleeding. Five patients (3.33%) demonstrated positive findings of OSA at 6 months or longer after postpharyngeal flap surgery. CONCLUSION: When coupled with a thorough preoperative evaluation by specialized personnel, pharyngeal flap surgery is a safe and reliable option for the surgical management of VPI.

Post-operative use of remoulding orthoses following cranial vault remodelling: a case series.

The use of external orthoses following surgical cranial vault remodelling in infants with craniosynostosis was first described in the 1980s. While a few preliminary reports have been published on its use, there are no reports outlining specific orthotic considerations. The purpose of this paper is to present the orthotic community with an introduction to the various craniosynostoses, the resultant cranial morphologies, and specific orthotic considerations associated with these morphologies, including trigocephaly, frontal plagiocephly, brachycephaly, scapholocephaly, and occipital plagiocephaly. For each presentation, guidelines are presented as to where the cranial remoulding orthosis should maintain contact, thereby discouraging cranial growth, and where the voids should be established and maintained to allow for corrective cranial growth. Principles are supported by photographs of representative cases.

International trends in the treatment of cleft lip and palate.

This article presents a contemporary (2004) survey of the methods and timing used in the care of cleft patients. The results are compared, when possible, with those of a similar study published by the lead author in 1998 and with those of the Eurocleft Project that took place from 1996 to 2000. Although very little uniformity is seen in the care of cleft patients, this comparison demonstrates a significant degree of agreement on many aspects of cleft care and a continuing process of adaptation and evolution in the field of cleft lip and palate surgery.

Postsurgical use of prosthetic palatal appliances. Two case reports.

Patients with cleft lip or palate encounter a myriad of difficulties in their early years of life, some of which begin at birth. The defect often impairs suckling and deglutition in the neonate. It can hinder appropriate speech development and may impose undue social and psychological stresses. Surgical and orthodontic interventions are essential and prosthetic palatal appliances play an important role not only throughout the patient's treatment course, but also in the treatment of unfavorable surgical sequelae.

The use of hydroxyapatite cements in craniofacial surgery.

Hydroxyapatite cements are a useful adjunct in treatment of deficiencies of the craniofacial skeleton. They provide a rapid and reliable method of correcting bony defects or contour deformities. Although they are alloplastic, their high degree of tissue tolerance and their demonstrated ability to incorporate within host bone make problems such as infection and extrusion rare. As with any alloplast, sound surgical principles should be used to avoid these complications. There should always be an acceptable overlying soft tissue envelope and minimal contamination of the operative site. Theoretical concerns about potential growth disturbance have not been borne out in experimental studies or by clinical experience.However, more extensive follow-up of patients will be needed to resolve these issues.

Correction of secondary cleft lip deformities.

LEARNING OBJECTIVES: After studying this article, the practitioner should be able to (1) describe the common secondary deformities of the cleft lip, (2) determine the appropriate timing for surgical intervention to correct the deformities, and (3) determine the best method of addressing each of the individual secondary deformities of the cleft lip. Secondary deformities are common in children born with a cleft lip and palate. Patients with cleft lip deformity will undergo multiple surgical procedures early in life, so it is imperative to prioritize treatment of their secondary deformities and minimize the number of interventions needed. Of the many approaches used to correct these problems, surprisingly few work well consistently. As with all plastic surgery, the timing and procedure should be predicated on the severity of the deformity.

The management of orbitozygomatic fractures.

Orbitozygomatic injuries are among the most common fractures encountered by the plastic surgeon. Appropriate management depends on an accurate diagnosis, focusing on the physical examination and data from computed tomography scans. One must pay particular attention to the orbital component of this injury, as it is from this that so much of the morbidity relating to these fractures is incurred. As with all facial fractures, accurate reduction is paramount to a successful outcome. As many buttresses as are necessary should be visualized to ensure an anatomic reduction. The amount and location of fixation depend on the fracture anatomy.A successful outcome may be expected if these basic principles are followed.

Vertical facial distraction in the treatment of arhinia.

Arhinia is a rare congenital malformation characterized by lack of the formation of external and internal nasal structures. Restricted midfacial growth is secondary to the loss of the midfacial growth centers. Staged reconstruction of the nasal passage and external nose is required. Vertical distraction osteogenesis is a beneficial step in the overall reconstructive program. This provides for additional bone and soft tissue for both improved aesthetic facial proportions and later surgical interventions.

Cleft nasal deformity and rhinoplasty.

The cleft nasal deformity is a complex challenge in plastic surgery involving the skin, cartilage, mucosa, and skeletal platform. Ever since Blair and Brown first described the intricacies of the cleft pathology in 1931, the appropriate approach has been extensively debated in the literature with respect to timing, technique, and extent of surgical intervention. In this article, the authors review the literature and summarize the various modalities for achieving a successful rhinoplasty in the patient with a cleft nasal deformity.