Samuel Stal

Variation in IRF6 contributes to nonsyndromic cleft lip and palate

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial birth defect which results in lifelong medical and social consequences. While there have been a number of attempts to identify the genes responsible for this disorder, the results have not been consistent among populations and no single gene has been identified as playing a major susceptibility role. Van der Woude syndrome, a disorder characterized by lower‐lip pits with or without cleft lip/palate, results in many cases from mutations in the interferon regulatory factor 6 (IRF6) gene. Recently, Zucchero et al. [2004: N Engl J Med 351:769–780] detected an association between SNPs in IRF6 and NSCLP in a number of different populations. A subsequent study by Scapoli et al. [2005: Am J Hum Genet 76:180–183] confirmed this association in an Italian population. We examined the same SNPs as Scapoli et al. [2005] in our large, well‐characterized sample of NSCLP families and trios, and also detected an altered transmission of IRF6 alleles. This additional confirmation further strengthens the IRF6 association and suggests that IRF6 plays a role in NSCLP susceptibility.

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.

Otoplasty: evaluation, technique, and review.

Prominent ear deformity is the most common abnormality of the external ear. Over two hundred different techniques have been described to correct this deformity. Many of these techniques have proven successful in their ability to achieve high patient satisfaction despite the significant variations in these techniques. From this perspective otoplasty is a privileged procedure allowing the surgeon great latitude in his approach and ability to achieve patient satisfaction. Despite high patient satisfaction, each technique has inherent strengths and weaknesses. The art of otoplasty is in the ability to realize the strengths and weaknesses of a cadre of procedures so as to maximize benefit and minimize complication.Analysis and correction of prominent ears should be approached in a rational, step-wise fashion. The external ear is an infinitely complex structure with great variation between individuals and between the two sides of the same individual. Appropriate evaluation is essential to the application of the appropriate corrective technique. Our approach to otoplasty includes a careful evaluation and description of the deformity in the context of normative standards and the goal of symmetry. When the patient is judged to be sufficiently mature we proceed with an algorithmic application of cartilage-sparing techniques suited to the specific deformity. In this approach, correction of the prominent ear can go beyond patient satisfaction, maximizing outcome in form and symmetry.

Resorbable Mesh in the Treatment of Orbital Floor Fractures

A variety of materials have been used to reconstruct defects of the orbital floor. Autogenous materials such as bone and cartilage have the obvious drawback of the necessary donor site, whereas alloplastic implants carry the potential risk of infection, particularly when in communication with the maxillary sinus. Consequently, there has been interest in the use of resorbable alloplastic material that acts as a barrier until completely degraded. In this series, a total of 12 patients with orbital defects larger than 1 cm2 were treated by the placement of a resorbable mesh plate of polyglycolic and polylactic acid (Lactosorb). Of the total of 12 patients treated, 3 were lost to follow-up. Of the remaining 9 patients, the mean follow-up was 6 months, with the longest follow-up being 15 months and the shortest 1 month. Two patients developed enophthalmos. In each case, this measured 2 mm using Hertel exophthalmometry, and was present in the early postoperative period (less than 1 month). The cause of the enophthalmos in both patients was found to be a technical error in placement of the mesh. One patient developed an inflammatory reaction along the infraorbital rim requiring implant removal. This occurred at 7 months. From the above series, it is concluded that resorbable mesh is an acceptable material for reconstruction of the orbital floor in selected patients. It is believed that larger floor defects are better suited for nonresorbable alloplastic reconstruction, and that placement of the mesh over the infraorbital rim is unnecessary and places the patient at risk for a local inflammatory reaction.

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.

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.

Salvage of amputation stumps by secondary reconstruction utilizing microsurgical free-tissue transfer.

During a 2-year period, 15 lower and upper extremity amputees were treated by microsurgical free-tissue transfer in an effort to salvage their amputation stumps. Salvage of length and restoration of contour to aid in prosthetic rehabilitation were the two main indications for reconstruction. Included in the 15 transfers were 3 scapular free flaps, 11 latissimus dorsi musculocutaneous flaps, and 1 groin flap. Thirteen of the patients in this group were refitted with prostheses following reconstruction and did well with no pain or skin breakdown of the resurfaced stumps. The follow-up period on these patients averaged 16 months. One patient, in whom the flap succeeded, underwent stump soft-tissue revision and myodesis. One patient, in whom the flap failed, continued to develop recurrent ulceration in his stump. This clinical experience followed an extensive laboratory study of 12 above-knee amputation patients using noninvasive Doppler ultrasound measurements to determine weight-loading and interface-pressure distribution between the stump and the socket of the prostheses and their relation to stump length and circumference.

Fifty years of the Millard rotation-advancement: looking back and moving forward.

Summary: Of all the methods for repair of the unilateral cleft lip, none has gained as much popularity as the rotation-advancement. Millard’s original principle of 50 years ago continues to guide surgeons in closure of the cleft lip. Unlike earlier procedures, the brilliance of the rotation-advancement is that it permits individual manipulation and modifications while maintaining Millard’s original surgical and anatomical goals. Millard and many other surgeons have made modifications to adjust the procedure to each specific patient, to address some of its faults, and to gain new advantages. In this article, the authors review the techniques of Drs. Ralph Millard, Steve Byrd, Court Cutting, John Mulliken, and Samuel Stal. The variations from Millard’s original technique are highlighted, including a discussion of the benefits of each modification.

Cartilage warping: an experimental model.

Cadaveric cartilage was cut into blocks with a newly devised cartilage cutter. Over one-hundred pieces of cartilage were used to define a kinetics curve of cartilage warping. Kinetics curves were developed for a control group of cartilage blocks placed in saline-soaked gauze (n = 46). In addition, kinetics curves were developed for cartilage placed in hypotonic saline (n = 14), hypertonic saline (n = 14), and cyanoacrylate glue (n = 6). Photographs of all groups were taken at timed intervals in order to plot the cartilage warping. It was found that pieces of cartilage which were cut peripherally (n = 6) warped twice as much as those cut centrally (n = 40). This was significant to p = 0.001. Within 15 minutes, centrally cut pieces of cartilage warped to approximately 90 percent of their end warpage; on the other hand, peripherally cut pieces of cartilage required 30 minutes to warp 90 percent of their destined warpage. The variables used did not significantly alter the kinetics curves as compared with control.

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.