Cassio Eduardo Raposo-Amaral

Two-stage surgical treatment of severe cherubism.

Cherubism is an autosomal-dominant syndrome characterized by excessive bilateral maxillomandibular bony degeneration followed by fibrous tissue hyperplasia. Eight patients (age, 6–15 years; mean, 11 years) with severe cherubism were treated with a 2-stage operation by the same senior surgeon (C.M.R.-A.) over an 18-year period, 1987 through 2005. Severity was based on a modified Motamedi classification system. The diagnosis was established clinically, radiographically, and histologically. Postoperative follow up ranged from 2 to 18 years (mean, 5.1 years). All patients underwent 2-stage surgical treatment. In the first stage, the anterior wall of the maxilla was osteotomized and removed (n = 5). The cherubic lesion was curetted from the maxilla and orbits. The maxilla was recontoured on the back table and then fixed orthotopically with wires. Alternatively, cortical bone windows were created, the maxillary and orbital lesions were curetted, and the maxilla was infractured and recontoured in situ with manual pressure (n = 3). Six months after the maxillary/orbital procedure, all patients underwent second-stage curettage and recontouring of the mandible using bony access windows and manual infracture. Satisfactory esthetic results were achieved in all patients. The patients remained clinically and radiographically disease-free throughout the follow-up period. The most profoundly affected patient sustained bilateral lower eyelid ectropion that resolved with full-thickness skin grafting. Although cherubism tends to abate by the fourth decade of life, early 2-stage surgical curettage provides a simple and reliable treatment that not only delivers immediate results, but also seems to arrest the growth of any remaining cherubic tissue.

Human Stem Cell Cultures from Cleft Lip/Palate Patients Show Enrichment of Transcripts Involved in Extracellular Matrix Modeling By Comparison to Controls

Nonsyndromic cleft lip and palate (NSCL/P) is a complex disease resulting from failure of fusion of facial primordia, a complex developmental process that includes the epithelial-mesenchymal transition (EMT). Detection of differential gene transcription between NSCL/P patients and control individuals offers an interesting alternative for investigating pathways involved in disease manifestation. Here we compared the transcriptome of 6 dental pulp stem cell (DPSC) cultures from NSCL/P patients and 6 controls. Eighty-seven differentially expressed genes (DEGs) were identified. The most significant putative gene network comprised 13 out of 87 DEGs of which 8 encode extracellular proteins: ACAN, COL4A1, COL4A2, GDF15, IGF2, MMP1, MMP3 and PDGFa. Through clustering analyses we also observed that MMP3, ACAN, COL4A1 and COL4A2 exhibit co-regulated expression. Interestingly, it is known that MMP3 cleavages a wide range of extracellular proteins, including the collagens IV, V, IX, X, proteoglycans, fibronectin and laminin. It is also capable of activating other MMPs. Moreover, MMP3 had previously been associated with NSCL/P. The same general pattern was observed in a further sample, confirming involvement of synchronized gene expression patterns which differed between NSCL/P patients and controls. These results show the robustness of our methodology for the detection of differentially expressed genes using the RankProd method. In conclusion, DPSCs from NSCL/P patients exhibit gene expression signatures involving genes associated with mechanisms of extracellular matrix modeling and palate EMT processes which differ from those observed in controls. This comparative approach should lead to a more rapid identification of gene networks predisposing to this complex malformation syndrome than conventional gene mapping technologies.

Changing face of cleft care: specialized centers in developing countries.

The organization and management of specialized cleft lip and palate centers in developing countries are challenging because of the lack of financial resources devoted to the national health care system. The treatment of cleft lip and palate is of low priority for health care and budgets; however, gradual progress is possible. As an example of how care might be improved in the developing world, we suggest guidelines to strengthen the local cleft lip and palate centers in Brazil based on the ideal geographic distribution of cleft centers around the country, to achieve the following objectives: first, avoid patients migration; second, facilitate patients adherence; third, focus on a global and continuous multidisciplinary treatment; and fourth, avoid indiscriminate opening of nonprepared cleft lip and palate centers in our country. This ideal scenario would put the cleft lip and palate health attention on the right path in Brazil.

Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate

Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88×10−2–5.02×10−9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show for the first time that cellular defences against DNA damage may take part in determining the susceptibility to NSCL/P. These results are in accordance with the hypothesis of aetiological overlap between this malformation and cancer, and suggest a new pathogenic mechanism for the disease.

Late cutaneous lip height in unilateral incomplete cleft lip patients does not differ from the normative data.

BackgroundCharacterizing the cutaneous upper lip height changes after unilateral cleft lip repair is very important to plan the surgical maneuvers, anticipate the need for overcorrection of the vertical dimension of the lips, and instruct the family on the postoperative outcomes. The aim of this study was to objectively analyze the asymmetry of upper lip height in patients with unilateral incomplete cleft lip who underwent Cutting extended Mohler repair. MethodsA prospective study of consecutive patients with unilateral incomplete cleft lip who underwent primary lip repair without facial orthopedics was performed. Fifty children without craniofacial abnormalities were used as a control. Frontal view photographs taken at the preoperative (T0) period and early (3–5 months; T1) and late (12–14 months; T2) postoperative periods were used to measure the cutaneous upper lip height. A comparative analysis between affected and unaffected lip heights (control group: right and left sides, respectively) was accomplished using a computerized photogrammetric evaluation. ResultsThe patients with cleft lip (n = 9) showed a significant (P < 0.01) progressive reduction in lip asymmetry within the studied period (T0 > T1 > T2). The lip asymmetry was higher (P < 0.01) in the cleft lip group (n = 9) than in the control group (n = 50), except in the T2 period (P > 0.05). The average improvement of lip height during the first year after surgery was 9%. ConclusionsThere is a progressive reduction in lip asymmetry following primary lip repair. Patients with unilateral incomplete cleft lip presented lip height average similar to children with noncleft lip in the late postoperative period.

Patient-reported Quality of Life in Highest-functioning Apert and Crouzon Syndromes: A Comparative Study

Background: Crouzon and Apert syndromes are the most common syndromic forms of craniofacial dysostosis. Apert syndrome has a broad clinical spectrum, including complex craniofacial involvement, as well as limiting deformities of the hands, feet, and other joints that require multiple surgical procedures when compared with Crouzon syndrome, which is generally less severe. The authors hypothesized that the quality of life of Apert syndrome patients is inferior to that of Crouzon syndrome patients. Methods: The quality of life of Apert (n = 8) and Crouzon (n = 12) syndrome patients was assessed using the World Health Organization Quality of Life-100 questionnaire. The Mann-Whitney test was used to compare the quality-of-life scores between Apert and Crouzon patients. Values were considered significant for a confidence interval of 95 percent (p < 0.05). Results: Apert patients showed an overall higher (score > 60 percent) quality of life in most World Health Organization Quality of Life-100 facets (68 percent) and domains (83.33 percent), with significance (p < 0.05) in three facets (energy and fatigue, mobility, and environment in the home), compared with Crouzon patients. Conclusion: Contrary to the authors’ initial hypothesis, both the highest-functioning Apert patients and the Crouzon patients presented a satisfactory quality of life, demonstrating that these syndromic patients had acquired the necessary repertoire to manage the adverse daily situations of their lives.

A subcranial Le Fort III advancement with distraction osteogenesis as a clinical strategy to approach pycnodysostosis with midface retrusion and exorbitism.

Pycnodysostosis is a rare autosomal recessive skeletal disorder involving a constellation of craniofacial manifestations including midface retrusion. We report the case of a 13-year-old girl with pycnodysostosis who presented with exorbitism, midface retrusion, malocclusion, and obstructive sleep apnea. Here, we describe the successful use of subcranial Le Fort III advancement using distraction osteogenesis with internal Kawamoto distracters. After a latency of 5 days, distraction for 10 days, and consolidation for 12 weeks, her midface was advanced by 10 mm with slight overcorrection at the occlusion level. At 2 years postoperatively, the patient had complete remission of her sleep apnea, resolution of her exorbitism, and amelioration of her class III malocclusion to class I. To the best of our knowledge, this is the first report of a successful subcranial Le Fort III midface advancement with distraction osteogenesis for craniofacial reconstruction of a pycnodysostosis. Our report highlights the surgical options that have been described for this craniofacial deformity and presents a novel and expedient approach for patients with pycnodysostosis presenting with exorbitism, midface retrusion, and/or sleep apnea.

Lip Height Improvement during the First Year of Unilateral Complete Cleft Lip Repair Using Cutting Extended Mohler Technique.

Objective. To compare the cutaneous lip height at early and late postoperative periods and to objectively determine the average amount of lip height improvement during the first year of unilateral complete cleft lip repair using Cutting extended Mohler technique. Methods. In this prospective cohort study, 26 unilateral complete cleft patients and 50 noncleft subjects were included. Photographs were taken between 12 and 16 weeks (T1) and also taken between 12 and 13 months after surgery (T2). The cutaneous lip height distance (photogrammetric lip analysis) obtained in these two periods of time were measured and statistically analyzed. Results. The average lip heights were 24% ± 9% in T1 and 8% ± 6% in T2 (P < 0.01). The average lip height asymmetry in the noncleft individuals was 4.52% ± 1.89%. Conclusion. Since all principles to obtain a symmetrical Cupids bow were performed, the postoperative pull-up of Cupids bow is probably owed to the scar contracture, which improves by 2 times during the first year after surgery.

Age at Surgery Significantly Impacts the Amount of Orbital Relapse following Hypertelorbitism Correction: A 30-Year Longitudinal Study

Background: The aim of this study was to identify variables that affect orbital relapse after hypertelorbitism correction. Methods: The authors retrospectively reviewed the medical records of patients who underwent hypertelorbitism correction at a single institution between 1975 and 2005. Bony interorbital distance was measured postoperatively and at long-term follow-up. Orbital relapse was defined as the difference between bony interorbital distance measurements at these time points. Patients were stratified into groups based on age at primary surgical correction (early, <8 years; late, ≥8 years), the severity of the initial deformity (moderate, bony interorbital distance ≤40 mm; severe, bony interorbital distance >40 mm), and the type of surgical technique used (facial bipartition versus box osteotomy). Differences in relapse between the stratified groups were analyzed using paired t tests. Results: A total of 22 patients met inclusion criteria for this study. Patients who underwent surgery before 8 years of age had a significantly higher degree of orbital relapse compared with older patients (5.9 mm versus 1.8 mm; p = 0.0142). There was no significant difference in orbital relapse based on the severity of the deformity or the operative technique used. Conclusions: Surgical correction of hypertelorbitism in patients younger than 8 years leads to a significantly higher rate of bony interorbital distance relapse compared with patients who undergo surgery at an older age. Neither the initial degree of severity nor the type of surgical technique correlates with relapse. The authors therefore recommend that in the absence of urgent factors necessitating early intervention, hypertelorbitism correction should be performed after 8 years of age.

Alveolar osseous defect in rat for cell therapy: preliminary report

PURPOSE To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm(2) of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS The average area of the alveolar defect at time point of 2 weeks was 22.27 +/- 1.31 mm(2) and the average area of alveolar defect at time point of 4 weeks was 9.03 +/- 1.17 mm(2). The average amount of bone formation at time point of 2 weeks was 5.73 +/- 1.31 mm(2) and the average amount of bone formation at time point of 4 weeks was 19 +/- 1.17 mm(2). Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.