Time filter

Source Type

Molck M.C.,University of Campinas | Vieira T.P.,University of Campinas | Sgardioli I.C.,University of Campinas | Simioni M.,University of Campinas | And 4 more authors.
European Journal of Medical Genetics | Year: 2013

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, with a highly variable phenotype. This chromosomal region contains low copy repeat (LCR) sequences that mediate non-allelic homologous recombination which predispose to copy number abnormalities at this locus. This article describes three patients investigated for suspicion of 22q11.2DS presenting atypical copy number abnormalities overlapping or not with the common ~3Mb deletion. They were investigated by G-banding karyotype, Multiplex-ligation dependent probe amplification (MLPA) and array Genomic Hibridization (aGH). Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. Atypical chromosomal abnormalities were detected: 3.6Mb deletion at 22q11.21-q11.23 between LCRs B-F in patient 1 and approximately 1.5Mb deletion at 22q11.21-q11.22 between LCRs D-E in patients 2 and 3. The breakpoints detected in patient 1 have not been previously described. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 region and corroborates the idea that genetic modifiers contribute to the phenotypic variability observed in proximal and distal 22q11.2 deletion syndromes. © 2013 Elsevier Masson SAS.


Da Silva Freitas R.,Federal University of Paraná | Da Silva Freitas R.,Assistance Center for Cleft Lip and Palate | Alonso N.,University of Sao Paulo | Busato L.,Assistance Center for Cleft Lip and Palate | And 4 more authors.
Journal of Craniofacial Surgery | Year: 2010

INTRODUCTION: Number 3 cleft or oral-nasal-ocular cleft is a well-known entity that was described by Morian over a century ago. This malformation is a paranasal-medial orbitomaxillary cleft running across the lacrimal segment of the lower eyelid and over the lacrimal groove. The Tessier number 3 naso-ocular cleft represents one of the most difficult and challenging malformations to correct for the reconstructive surgeon. We have conducted a retrospective analysis of our series consisting of 21 cases. OBJECTIVE: The objective was to review the functional outcome and aesthetic results of the different techniques applied for each case. MATERIALS AND METHODS: From 1997 to 2007, 21 patients with a Tessier number 3 cleft were treated in our craniofacial units. The clinical findings, tomographic studies, and surgical procedures were reviewed and analyzed. We have discussed our protocol of the treatment. RESULTS: We have treated facial malformation in 2 craniofacial centers. Fourteen patients were evaluated in the first year of their life, with an average age at presentation of 3 years. Twelve patients were female, and 9 were male; 6 patients had amniotic bands in limbs, 5 patients had an association with Tessier number 11 cleft, 3 patients with number 9 cleft, and 1 with number 7 cleft. Related to cleft lip, 10 patients had bilateral cleft lip, and 8 patients had unilateral cleft lip. Three patients did not have any involvement of the upper lip. The alar base was deviated upward in 19 patients, 11 cases had severe anatomic alteration with the lateral border of the ala above the medial canthus, and 8 cases had a mild dislocation. Nine cases of lacrimal duct obstruction and 8 cases of lacrimal duct extrophy were identified. Twelve patients had a lower eyelid coloboma of varying grades, and there were 2 cases of microblepharia. Aiming the soft tissue reconstruction, eyelid, nose, and upper lip were evaluated regarding their position, absence of tissue, and position of medial canthus and ala. Twelve of our patients underwent correction in the same moment, their medial canthus rotated upward and the ala downward, using the contralateral side as the reference. The lip was treated using a Millard-like technique. Neo-conjunctivorhinostomy was performed in the same moment in 2 patients or later in 1 case. Four patients had plagiocephaly due to the cranial involvement, and they were submitted to cranioplasty. Three had neurosurgical approach and advancement of the frontal bandeau. One adult patient received an acrylic plate to reshape the frontal area. CONCLUSIONS: Tessier number 3 cleft is one of the most difficult and challenging malformations to correct for the reconstructive surgeon. Besides the difficulties of its treatment, patients with Tessier number 3 cleft may achieve good results when the team has good skills. Copyright © 2010 by Mutaz B. Habal.


Souza J.,Assistance Center for Cleft Lip and Palate | dal Vesco K.,Assistance Center for Cleft Lip and Palate | Tonocchi R.,Assistance Center for Cleft Lip and Palate | Closs-Ono M.C.,Federal University of Paraná | And 3 more authors.
American Journal of Medical Genetics, Part A | Year: 2011

Richieri-Costa and Pereira syndrome is a rare autosomal recessive disorder characterized specially by Pierre Robin sequence with cleft mandible and limb anomalies. There are a typical laryngeal anomaly which encompass short and round larynx, absent or abnormal epiglottis, and abnormal aryepiglottic folds. Most patients reported were from Brazil. We describe a brother and sister with Richieri-Costa and Pereira syndrome on another Brazilian family documenting their physical findings and laryngeal defects. We also review the literature and discuss the main clinical characteristics and etiology. © 2011 Wiley-Liss, Inc.


Buonocore S.,Yale University | Broer P.N.,Yale University | Walker M.E.,Yale University | Da Silva Freitas R.,Federal University of Paraná | And 3 more authors.
Annals of Plastic Surgery | Year: 2014

Background: Macrostomia is a rare facial cleft, with an incompletely described pathogenesis. This series highlights cases of isolated macrostomia presenting with several distinct phenotypes. We examine phenotypic differences in macrostomia patients, to further elucidate the etiopathogenesis. Materials and Methods: We performed a retrospective review of macrostomia patients evaluated during a 10-year period. Patient demographics and clinical features are reported. Results: We identified 25 macrostomia patients (13M/12F). Right-sided macrostomia occurred in 15, left-sided macrostomia occurred in 6, and bilateral macrostomia occurred in 4 patients. Of the bilateral cases, 100% existed in isolation of craniofacial microsomia (CFM) or other craniofacial abnormalities. Twelve patients presented with macrostomia in isolation of CFM; in this subgroup, the male-to-female ratio was 1:1. Bilateral macrostomia was present in 33% of patients. Unilateral macrostomia occurred more often on the right (5:2). Phenotypes included simple unilateral or bilateral macrostomia (67%), macrostomia associated with severe diastasis of the cheek musculature (8%), macrostomia associated with lateral facial clefts (17%), and diastasis of cheek musculature without significant macrostomia (8%). Conclusions: Macrostomia seen in isolation of CFM presents in phenotypically distinct forms. It is unlikely that a single mechanism is responsible for this range of phenotypes.We believe that both intrauterine trauma and failure of fusion of the mandibular and maxillary processes secondary to an aberration in FGF8 function are responsible. Additionally, diastasis of facial musculature may result from delayed fusion and subsequent decreased mesodermal penetration of the mandibular and maxillary processes. Copyright © 2012 by Lippincott Williams & Wilkins.


da Silva Freitas R.,Assistance Center for Cleft Lip and Palate | da Silva Freitas R.,Federal University of Paraná | Alonso N.,University of Sao Paulo | de Freitas Azzolini T.,Federal University of Paraná | And 4 more authors.
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2010

Absence of half-nose is an extremely rare congenital malformation, which has a devastating impact on the patient and the family. A review of indexed English-language literature found 91 cases of half-nose, including 50 patients with proboscis lateralis. Pathogenesis is not clear, and the reported cases have sporadically occurred. Many aspects must be considered when reconstructing a congenital half-nose, such as timing of surgery, type of tissue to be used and the need to reconstruct nasal airway. The aim of this article is to present personal experience in seven cases of half-nose reconstruction, in order to review the literature regarding to this rare entity, highlighting aspects of incidence, pathogenesis and surgical treatment. Nasal reconstruction was performed at ages of 5-7 years to minimise psychological trauma. Forehead skin demonstrated to be an excellent donor site to re-surface the nose. For the inner lining, contralateral cutaneous nasal flap was our preference. Concerning the nasal framework reconstruction, alar contour was restored using a cartilage graft from the lower portion of ear tragus and concha. © 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons.


Laverde B.L.B.,Federal University of Paraná | Da Silva Freitas R.,Federal University of Paraná | Nasser I.J.G.,Assistance Center for Cleft Lip and Palate
Journal of Craniofacial Surgery | Year: 2016

Introduction: Unilateral cleft lip (UCL) patients have lip and nose deformities that must be addressed during lip repair. Currently, devices to achieve lip and nose improvements have been developed. The most researched presurgical molding device is the nasoalveolar molding (NAM), which has shown favorable results. However, clinical observation shows that unilateral cleft patients, even without molding devices, achieve spontaneous improvements. The aim of this study is to compare morphological and symmetry changes in nose and lip, between patients less than 30-day old and those submitted to cheiloplasty, at 6 months of age. Materials and Methods: A total of 27 UCL patients with 2 photographs were selected. The pictures were taken from frontal view and nasal base view at 2 distinct moments: before 30 days of life (t1) and at 6 months of age, during cheiloplasty surgery (T2). Images were analyzed with indirect measurement to assess lip and nose dimensions and nasal symmetry. ImageJ software was used to perform the analyses. Results: A total of 20 patients (P<0.05) had an average cleft width reduction of 15% [standard deviation (SD)±11%]. A 55% average increase (SD±29%) was observed in nostril height of cleft side in 16 of patients (P<0.05). There was an reduction in facial asymmetry of nostril width (P<0.05), from 95% (SD±90%) (t1) to 59% (SD±50) (T2). Also, nasal base width asymmetry (P<0.05) was decreased from 64% (SD±66%) (t1) to 40% (SD±29%) (T2). Conclusion: Facial growth causes a natural improvement on cleft morphological changes and nasal symmetry. Copyright © 2015 by Mutaz B. Habal, MD.


Canan L.W.,Assistance Center for Cleft Lip and Palate | Da Silva Freitas R.,University of Sao Paulo | Alonso N.,Federal University of Paraná | Tanikawa D.Y.S.,Assistance Center for Cleft Lip and Palate | And 2 more authors.
Journal of Craniofacial Surgery | Year: 2012

Background: The conventional methods of maxillary alveolar reconstruction in patient with cleft are the periosteoplasty and autologous bone grafting. As an important alternative of bone substitution, there is the recombinant human bone morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with periosteoplasty and autologous bone grafting. Methods: Patients with cleft and alveolar defect were divided into 3 groups of 6 patients who underwent to autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and periosteoplasty, respectively. The analysis was performed through computed tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The variables analyzed were the alveolar defect volume, formed bone volume, bone formation rate, maxillary height repair rate, and the formed bone density mean. Results: The formed bone volume was similar comparing the bone graft and BMP groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed bone volume significantly larger than the periosteoplasty group at 3 and 6 months postoperatively. In this last group, the 1-year follow-up was canceled because the bone formation was insufficient. The bone formation rate, the maxillary height repair rate, and the mean of density of the formed bone were similar in the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90, and 0.81, respectively. Conclusions: The amount of formed bone in the periosteoplasty group was insufficient. There was no difference among the bone graft and rhBMP-2 therapy considering the parameters analyzed. Copyright © 2012 Mutaz B. Habal, MD.


Molck M.C.,University of Campinas | Vieira T.P.,University of Campinas | Simioni M.,University of Campinas | Sgardioli I.C.,University of Campinas | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

The 22q11 chromosomal region contains low copy repeats (LCRs) sequences that mediate non-allelic homologous recombination, which predisposes to copy number variations (CNVs) at this locus. Hemizygous deletions of the proximal 22q11.2 region result in the 22q11.2 deletion syndrome (22q11.2 DS). In addition, 22q11.2 duplications involving the distal LCR22s have been reported. This article describes a patient presenting a 2.5-Mb de novo deletion at proximal 22q11.21 region (between LCRs A-D), combined with a 1.3-Mb maternally inherited duplication at distal 22q11.23 region (between LCRs F-H). The presence of concomitant chromosomal imbalances found in this patient has not been reported previously. Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 deletion syndrome and highlights the difficulty to make genetic counseling and predict phenotypic consequences in these situations. © 2014 Wiley Periodicals, Inc.


Alonso N.,University of Sao Paulo | Tanikawa D.Y.S.,University of Sao Paulo | Freitas R.D.S.,Assistance Center for Cleft Lip and Palate | Canan Jr. L.,Assistance Center for Cleft Lip and Palate | And 2 more authors.
Tissue Engineering - Part C: Methods | Year: 2010

Introduction: A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. Methods: Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. Results: Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). Conclusions: For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting. © 2010, Mary Ann Liebert, Inc.


PubMed | Assistance Center for Cleft Lip and Palate
Type: Comparative Study | Journal: The Journal of craniofacial surgery | Year: 2012

The conventional methods of maxillary alveolar reconstruction in patient with cleft are the periosteoplasty and autologous bone grafting. As an important alternative of bone substitution, there is the recombinant human bone morphogenetic protein-2 (rhBMP-2). This study compares the rhBMP-2 with periosteoplasty and autologous bone grafting.Patients with cleft and alveolar defect were divided into 3 groups of 6 patients who underwent to autologous iliac crest bone grafting, resorbable collagen sponge with rhBMP2, and periosteoplasty, respectively. The analysis was performed through computed tomographic scan preoperatively and at months 3, 6, and 12 postoperatively. The variables analyzed were the alveolar defect volume, formed bone volume, bone formation rate, maxillary height repair rate, and the formed bone density mean.The formed bone volume was similar comparing the bone graft and BMP groups at 1-year postoperative analysis (P = 0.58). Both of them had the formed bone volume significantly larger than the periosteoplasty group at 3 and 6 months postoperatively. In this last group, the 1-year follow-up was canceled because the bone formation was insufficient. The bone formation rate, the maxillary height repair rate, and the mean of density of the formed bone were similar in the bone graft and BMP groups at 1-year follow-up with P values of 0.93, 0.90, and 0.81, respectively.The amount of formed bone in the periosteoplasty group was insufficient. There was no difference among the bone graft and rhBMP-2 therapy considering the parameters analyzed.

Loading Assistance Center for Cleft Lip and Palate collaborators
Loading Assistance Center for Cleft Lip and Palate collaborators