维甲酸诱导腭裂相关wnt和成纤维细胞生长因子配体表达的动态变化

目的 筛选与维甲酸诱导腭裂相关的wnt和成纤维细胞生长因子(FGF)信号分子,观察其在正常腭突发育和维甲酸诱导腭裂形成不同阶段的表达动态变化.方法建立维甲酸诱导腭裂小鼠模型,制作基因芯片并筛选wnt和FGF信号通路相关基因.根据芯片结果选出wnt经典通路配体wnt3和wnt8a、FGF通路配体fgf9和faf10,并应...     

Double tongue, intraoral anomalies, and cleft palate--case reports and a discussion of developmental pathology.

OBJECTIVE: Isolated cleft palate is the most common presentation of the nonsyndromic cleft lip/palate combinations and is multifactorial in etiology. We report two cases of children with clefts of the secondary palate coexistent with double tongue and in either case mandibular epulis or superiorly displaced salivary gland. RESULTS AND DISCUSSION: In each case, the palatal cleft correlated anatomically with the intraoral space-occupying lesion. The ratio of tongue volume to intraoral volume during palatogenesis is discussed with reference to the pathogenesis of cleft palate. These clinical cases propose the model of a unifying sequence of developmental events whereby deformation of palatal shelf elevation results in secondary palatal clefting.     

Investigations on the Palatal Rugae Pattern in Cleft Patients

The study investigated the relationship of the palatal rugae to points and distances of the cleft palate during the time period from birth to early mixed dentition in subjects with unilateral and bilateral cleft lip and palate by means of a three-dimensional measuring system. The changes identified in the distances from the lateral palatal rugae points of the first and third rugae to the incisal point, the canine point and the tuberosity line made it possible to assess how growth and the various forms of therapy applied affected the position of the palatal rugae during the study period (from birth to early mixed dentition). Changes in the linear distances from the palatal rugae to the maxillary measuring points were identified during preoperative therapy, after lip surgery, and after palate surgery. A comparison of the distances from the palatal rugae with distances between equivalent points (incisal point-canine point, canine point-tuberosity line, canine point-canine point) revealed differences in some instances. The results suggest that the palatal rugae in combination with measuring points of the cleft palate can serve to depict the changes occurring in the anterior palate during various stages of therapy and growth.     

Long-term evidence for favorable midfacial growth after delayed hard palate repair in UCLP patients.

OBJECTIVE: To investigate whether delayed hard palate repair resulted in better midfacial growth in the long term than previously achieved with "conventional" surgical methods of palatal closure. DESIGN AND SETTING: Long-term cephalometric data from patients with unilateral cleft lip and palate were available from two Scandinavian cleft centers. The patients had been treated by different regimens, particularly regarding the method and timing of palatal surgery. Patients were analyzed retrospectively, and one investigator digitized all radiographs. PATIENTS: Thirty consecutively treated subjects from each center, with cephalograms taken at three comparable stages between 10 and 16 years of age. RESULTS AND CONCLUSIONS: Patients whose hard palates were repaired late (early soft palate closure followed by delayed hard palate repair at the stage of mixed dentition) had significantly better midfacial development than patients in whom the hard palate was operated on early with a vomer flap, and then during the second year of life, the soft palate was repaired with a push-back procedure. As the growth advantage in the delayed hard palate repair group was accomplished without impeding long-term speech development, the delayed repair regimen proved to be a good alternative in surgical treatment of patients with unilateral cleft lip and palate.     

Comparative study of maxillary growth and occlusal outcome after autogenous rib grafting in complete cleft palate defect

Cleft palate is a congenital deformity with soft tissue and hard tissue defects. Normal cleft palate repairing surgery only repairs soft tissue defects, whereas bone defects in the hard palate still exist. Therefore, we conducted this study in beagles to observe the influence of bone grafting at primary surgery on craniofacial growth and occlusal relationships in individuals with complete cleft palate and to provide experimental evidence for optimal surgical procedures for cleft palate.Using 60 beagle puppies as subjects, we tested the effects of bone grafting in surgically induced palatal defect. The animals were randomly and equally divided into four groups: (1) unoperated controls; (2) surgically induced unilateral cleft palate, not repaired; (3) two-flap palatoplasty used to close the soft defect of the surgically induced cleft palate; (4) autogenous bone (a piece of rib bone) implanted into the palatal defect before two-flap palatoplasty was performed.Cephalometric roentgenography and plaster casts of the maxillary were taken preoperatively and every 4 weeks after surgery. Sixty metric cranial variables were measured directly from the cleaned skulls after the animals were killed the 34th week postoperatively.The measurement results indicated that bone grafting may reduce the disturbance of maxillary growth caused by the cleft palate and the denuded bone, but it may cause other maxillary deformities. This finding suggests that surgeons should be careful in choosing the method of primary bone grafting in repairing complete cleft palate.     

The mathematical modelling of the displacement of the hard palate tissues in conservative uranoplasty

Presents a mathematical model of sparing uranoplasty techniques developed by the authors; using this model, a physician may assess before surgery the volume of tissues needed to close the palatal defect. Experience gained with 72 surgeries carried out in children with unilateral cleft palate confirms the desirability of preliminary computations. Mathematical models for the most prevalent sparing uranoplasty methods are offered.     

Dental Arches and Occlusion in Bilateral Cleft Lip and Palate Patients after Two Different Routines for Palatal Surgery

Background: Delayed hard palate repair (DHPR) is believed by many researchers to improve maxillary growth and facial appearance in patients born with cleft lip and palate. However, only few studies dealing with the midfacial growth outcome after this type of surgery in bilateral cleft patients have been published. Patients and Method: The purpose of this retrospective study was to compare long-term results of maxillary morphology, dental arches and occlusion in two groups of patients with bilateral cleft lip and palate. The palatal surgery differed between the two groups, particularly with respect to the timing of hard palate repair. The DHPR group (n=16) underwent soft palate closure at 12 months and hard palate repair at around 8 years, whereas the early palatal repair group (EPR) (n=12) had completed two-stage palatal closure during the first year of life. These latter subjects had undergone more traditional palatal surgery with vomer flaps for repair of the anterior part and push-back closure for the posterior part of the cleft. Surgery was performed in both groups by the same surgical team at Sahlgrenska University Hospital, Göteborg, Sweden. Dental casts were used to analyze the pre- and postoperative maxillary morphology, dental arch dimensions, and occlusion of both samples, which were followed longitudinally from infancy to early adulthood. Results: Differences recorded in both maxillary growth and occlusion were generally in favor of the DHPR group. However, major intragroup variations and relatively small sample sizes precluded statistical verification of the differences, except for development during the early stages.     

成人腭裂患者腭盖表面积和倾斜度的比较研究

目的:观察腭裂患者上颌骨是否具有正常的生长发育潜能.方法:应用三维CT扫描成像系统,对比分析正常(牙合)成人、单侧完全性唇腭裂均已手术修补组以及腭裂未手术修补组成人患者的腭盖表面积和倾斜度.结果:腭裂未手术组的腭盖倾斜度显著高于正常对照组,腭盖向颅侧旋转,位置更加垂直;无论腭裂手术修补与否,腭裂患者的腭盖面积均显著小于正常对照组.结论:单侧完全性腭裂患者存在内在性的组织发育不足.     

The mechanism of palatal clefting in the Col11a1 mutant mouse.

The occurrence of cleft palate in mutant mice offers an opportunity to understand the possible role of specific genes in palatogenesis. Here, cleft palate in mice carrying the chondrodysplasia (cho) defect, which consists of an autosomal-recessive mutation in the collagen gene Col11a1, was investigated. The proposed cause of cleft palate in cho homozygous mice is failure of the palatal shelves to adhere and make contact due to mandibular growth abnormalities. Another cause of cleft palate that has recently been demonstrated in other animal models is failure of the midline epithelial seam forming between the shelves to undergo epithelial-mesenchymal transformation (EMT). The present strategy to test the likelihood of this second possibility was to culture the unfused cho/cho palatal shelves at different stages of development to see if they were capable of adhering and undergoing EMT in vitro. By using carboxydichlorofluorescein succinimidyl ester to trace the fate of the medial-edge epithelium (MEE), it was shown that cho/cho palates have full potential for MEE adherence and EMT up to embryonic day 17.5/18.5, when epithelia keratinize before birth, preventing the adherence of both the normal and homozygous palatal shelves. Thus, the major effect of the mutant collagen gene on the palate is likely to be via mandibular growth disruption. The possibility that unfused palatal shelves in other clinical syndromes can adhere and undergo EMT if brought into contact at appropriate times before birth has important therapeutic implications.     

单侧手术修复腭裂的初步报告

目的为减少对面型主体结构的损伤，延长患侧腭，采用单侧手术修复腭裂。材料与方法手术方法系只用患侧腭粘骨膜瓣修复裂隙，并做腭骨水平板切骨后移延长。本组手术26例，男性18例，女性8例；手术时年龄为6个月～8岁，平均22.5个月；裂隙宽度最大18mm，最小8mm，平均为12mm。结果手术患儿全部正常痊愈出院。无喉水肿、呼吸道感染、继发性出血、伤口裂开或穿孔等并发症。结论单侧手术可成功用于腭裂初期修复；减少对面型主体结构的损伤和瘢痕；使患侧短小的腭适当延长，与健侧协调一致。     

地塞米松诱导小鼠腭裂及E-钙黏素基因表达的研究

目的 建立地塞米松（DEX）诱发 C57BL/6J小鼠的腭裂模型,并在腭发育期间检测E-钙黏素基因的表达,探讨DEX诱发腭裂与E-钙黏素基因的相关性。方法 将孕鼠随机分为实验组和对照组,在小鼠E10.0—E12.0,连续3 d按体重分别给予孕鼠注射DEX（实验组）和生理盐水（对照组）,于E17.5在体视显微镜下检测各组腭裂的发生率;分别在E13.5、E14.5、E15.5、E17.5取胎鼠腭部组织行苏木精-伊红（HE）染色和免疫组织化学染色,观察腭部形态及E-钙黏素的表达情况;在E14.0、E14.5、E15.5时采用实时荧光定量聚合酶链反应检测2组腭突中E-钙黏素以及β-钙黏素 mRNA的表达水平。结果 DEX组腭裂发生率为43.59%（17/39）,对照组为3.03%（1/33）。DEX作用后,腭突体积明显缩小,上皮不能接触,E-钙黏素阳性表达于腭突间充质中。在E14.0、E14.5及E15.5,与对照组相比,实验组腭突E-钙黏素及β-钙黏素的表达均升高（P<0.05）。结论 DEX处理后,E-钙黏素在腭突间充质中异位表达,其基因表达上调,与其相结合的β-钙黏素表达量也增多,影响了间充质的增殖从而形成短小腭突导致腭裂。     

Increased fistula risk following palatoplasty in Treacher Collins syndrome.

OBJECTIVE: Patients with Treacher Collins syndrome have abnormal vascular supply to the palate, yet it is unknown whether there are increased postoperative healing problems following palatoplasty. This study investigated the correlation between Treacher Collins syndrome and postoperative palatal fistula formation. DESIGN: Retrospective chart review was performed. PATIENTS: Children undergoing palatoplasty at Children's Hospital Los Angeles from 1987 to 2000 were evaluated. Ten children with Treacher Collins syndrome, 92 children with other syndromes and cleft palate, and 458 nonsyndromic patients with isolated cleft palate were studied. INTERVENTIONS: All children were treated with a one-stage, double-reversing Z-plasty cleft palate repair. MAIN OUTCOME MEASURES: Outcome measures included intraoperative observations of surgical anatomy and postoperative clinic follow-up of fistula formation. Palatal fistula rates between patients with Treacher Collins syndrome, other syndromes, and no syndrome were compared with chi-square analysis. RESULTS: Children with Treacher Collins syndrome had significantly greater palatal fistula rates (50%) than children with other syndromes (8.7%) or no syndrome (4.1%). Treacher Collins patients demonstrated large palatal fistulas and poor flap vascularity. CONCLUSIONS: Children with Treacher Collins syndrome and cleft palate have significantly higher palatal fistula risk than other children with cleft palate when double-reversing Z-plasty palate repair is performed. Our findings suggest that children with Treacher Collins syndrome and cleft palate may have poor vascularity to palatal flaps created during palatoplasty. Furthermore, we recommend that surgeons performing palatoplasty minimize the dissection of mucoperiosteal flaps around the greater palatine arterial pedicle and utilize closure techniques creating the least vascular disruption of palatal tissue.     

腭裂实验动物模型的建立及缝牵张成骨的实验研究

目的 探讨手术建立腭裂实验动物模型及应用NiTiSMA牵张器行缝牵张成骨治疗发育期实验动物腭裂的可行性。方法 12只杂种犬被随机分为实验组和对照组，每组6只。采用自行设计、制作的表面处理的NiTiSMA牵张器，对发育期的腭裂实验动物（杂种犬）模型进行腭上颌缝牵张成骨，修复腭部裂隙区的全层组织缺损。观察裂隙关闭的过程。通过石膏模型，观察缝牵张成骨对上颌牙弓宽度发育的影响。结果 实验组动物腭部裂隙于牵张器植入14d后在腭中线处闭合。缝牵张成骨过程未对实验组动物牙弓宽度的发育造成明显影响。结论 表面处理的NiTiSMA牵张器运用牵张成骨原理，能有效地修复杂种犬腭裂动物模型的腭裂骨质缺损。     

Genetic background influences the capacity for medial edge epithelium disintegration and phenotype of cleft palate in TGFβ3 knockout mice

ObjectivesCleft palate is a frequent congenital craniofacial malformation of unknown etiology. Transforming growth factor (TGF) β3 is required for palatal shelf fusion. Although TGFβ3 knockout (KO) mice are widely used mouse models for cleft palate, cleft palate phenotypes differ among these mice. This study aimed to determine the effects of genetic background on the cleft palate phenotype in mice.MethodsWe produced TGFβ3 KO congenic mouse strains with five different genetic backgrounds. The phenotypes of the congenic strains were determined by visual examination. The capacity for disintegration of the medial edge epithelium (MEE) and basement membrane (BM) of palatal shelves of all five mouse strains was analyzed by using immunofluorescence staining after single palatal shelf suspension culture. The relationship between phenotype and disappearance of the MEE and BM was analyzed.ResultsAlthough the five congenic strains carried the same defective Tgfb3 gene, the fetal palate phenotypes differed among strains. The loss of the MEE cells and BM also differed with the genetic background, and the degree of such loss correlated with the cleft palate phenotype.ConclusionsThe cleft palate phenotype in mice is influenced by the genetic background, which governs the capacity for MEE and BM disintegration.     

Use of rotation flap in repair of cleft palate and velopharyngeal insufficiency

Although cleft palate anomaly is frequent, the criterion standards in surgical treatment have not been determined yet. There are a few techniques described for cleft palate repair owing to the limited tissue in the palatal mucosa, the rigid structure of the palatal mucosa, and the limited vascularity of the hard palate. In this study, a novel cleft palate repair technique based on separating the soft palate from the hard palate as a musculomucosal flap and using it as a rotation flap has been described. The operation is evaluated individually for each anomaly because variations occur in the surgical technique according to the extension of the cleft toward the teeth in the palate. This operation was performed on a total of 28 patients (17 girls and 11 boys) aged between 1.5 and 16 years and presented to our clinic. Patients were assessed for speech analysis outcomes, tympanogram values, hearing functions, magnitude of palatal lengthening during the operation, and rate of fistulae. Statistically significant differences in values of the speech analysis and the audiometric assessment were determined between before and 6 months after surgery. Complete recovery of otitis was observed 1 month after surgery without another treatment in 9 (42.8%) of 21 patients who were detected to have serous otitis media preoperatively. Tension-free closure, lower risk of fistula, good restoration of velopharyngeal functions, ability to be performed on all types of cleft palate, ability to provide a good intraoperative exposure, and being a single stage seem to be the most important advantages of this technique.     

Dental arch relationships following palatoplasty for cleft lip and palate repair

Palatal scarring is assumed to be a primary cause of facial growth derangement in cleft lip and palate. Evidence supporting this hypothesis is confounded by the clinical involvement of various surgeons, and therefore definitive conclusions are not possible. In this study, we investigated the dental arch relationship in two groups, Exposed (47 children; 11.2 yrs) and Unexposed (61 children; 11.2 yrs), with a unilateral cleft lip and palate operated on by the same surgeon. The technique of hard palate repair differed between the two groups. In the Exposed group, palatal bone of the non-cleft side only was left denuded, inducing scar formation. In the Unexposed group, a vomerplasty with tight closure of the soft tissues was applied. Three raters graded the dental arch relationship and palatal morphology using the EUROCRAN Index. The dental arch relationship in the Exposed group was less favorable than in the Unexposed group (p = 0.009). Palatal morphology in both groups was comparable (p = 0.323). This study demonstrates that reduction of denuded bony areas on the palate after palatal repair with a vomer flap had a favorable effect on the dental arch relationship. For palatal morphology, no effect of the type of palatal repair was found.     

四氯二苯对二恶英和地塞米松诱导小鼠腭裂及转化生长因子-β3和受体活化样激酶5的表达

目的建立四氯二苯对二恶英（TCDD）和地塞米松（DEX）联合诱导C57BL/6J小鼠腭裂模型,并在腭发育关键时期检测转化生长因子-β3（TGF-β3）和受体活化样激酶5（Alk5）基因的表达,探讨TCDD和DEX联合诱导胎鼠腭裂与TGF-β3和Alk5的相关性。方法在小鼠GD10 ～GD12,实验组小鼠连续3 d胃饲TCDD和腹腔注射DEX,空白对照组不做处理,于GD17.5体视显微镜下检测各组腭裂发生率,并于GD13.5、GD14.5、GD15.5 分别剪取胎鼠腭突提取RNA,采用实时荧光定量聚合酶链反应检测TGF-β3和Alk5基因表达。结果采用TCDD和DEX联合致畸,可诱导C57BL/6J胎鼠形成100%腭裂,建立了一种稳定适合分子生物学研究的腭裂动物模型。GD13.5时TGF-β3和Alk5基因表达水平在实验组与空白对照组之间差异均无统计学意义（P>0.05）,在GD14.5、GD15.5实验组TGF-β3表达均降低（P<0.05）,而Alk5表达均升高（P<0.05）。结论TCDD和DEX联合作用可诱导C57BL/6J胎鼠形成稳定腭裂,在腭融合关键时期诱导TGF-β3表达下降,Alk5表达升高,与腭裂的发生具有一定的相关性。     

Treatment protocol for unilateral cleft lip and palate patients: questioned by two case reports

BACKGROUND: The types and severity of clefts as well as palatal development and growth in children with repaired cleft lip and palate deformities can vary greatly. Independent of the technique used surgery produces scar tissue, which restricts palatal growth so that by the second decade many patients have an underdeveloped maxilla. Experience has shown that the maxillary retrognathism found in many cleft patients is not amenable to nonsurgical correction. Few long-term studies have evaluated the procedures, sequencing and timing of the treatment methods found to give the best results. This lack of reliable information means there is a serious gap in our ability to assess the value of different treatment modalities. AIMS AND METHODS: From the viewpoint of orthodontics, this article describes the treatment protocol used by the cleft lip and palate team at the University Hospitals of the KU Leuven. The present treatment protocol is illustrated and questioned by two cases. The roles of prediction of facial growth and distraction osteogenesis are discussed.