遗传性牙龈纤维瘤病（附2例报告）

目的通过探讨遗传性牙龈纤维瘤病（HGF）的临床特点及治疗方法,增进对本病的认识,从而提高诊断治疗水平。方法先证者法收集两个HGF家系全部成员资料,观察不同家系及同一家系不同个体的临床表型和发病特点,绘制系谱图,分析可能的遗传方式。对两名先证者采用手术治疗。结果两家系发病患者均符合非综合征型HGF特征。发病患者不同个体间的表现度不同。两家系均符合常染色体显性遗传特征。经随访,手术患者治疗效果良好。结论 HGF遗传方式以常染色体显性遗传为主,且同一家系的不同受累个体其增生程度轻重不一,极具差异,具有高度遗传异质性。手术是治疗该病的有效的方法。     

干扰素调节因子6基因致病的Van der Woude综合征的家系调查和遗传特点分析

目的 探讨中国人Van der Woude综合征（VWS）的临床表型及遗传学特点。方法 先证者法收集14个VWS家系并进行口腔专科检查、家系调查及基因突变分析,分析不同VWS家系个体或同一家系不同个体的临床表型,绘制家系图谱,明确遗传方式及致病基因,计算表型分布频率和表型基因频率。结果 VWS家系基本符合常染色体显性遗传特征,患者多数表现为典型的VWS,致病基因为干扰素调节因子6（IRF6）。VWS表型分布频率为：唇瘘91.9%,唇腭裂73.0%,牙畸形8.1%。不同家系个体和同一家系的不同个体临床表型存在明显差异。结论 收集的家系均为常染色体显性遗传,表现度变异大。中国人群VWS致病基因为IRF6,为Ⅰ型VWS。     

一个非综合征型多数牙缺失家系的临床及遗传学特征分析

目的:探讨一个非综合征型多数牙缺失家系的临床表型及遗传学特点.方法:对家系内部分患者及正常成员进行口腔专科检查和家系调查,总结分析其临床特征,并绘制系谱图以明确其遗传方式.结果:(1)该家系符合常染色体显性遗传模式,外显率较高;(2)患者牙列发育异常表现在牙齿数目、形态、位置及(牙合)关系等方面,先天缺牙以第二前磨牙及第三磨牙较为常见;(3)家系内不同个体的临床表型存在差异. 结论:该家系中,先天性缺牙呈常染色体显性遗传模式,外显率较高,表型差异较大.其临床特征以第二前磨牙和第三磨牙先天缺失较为多见.     

牙本质发育异常家系调查和表型分析

目的:调查和分析中国人牙本质发育异常家系及临床表型,进一步明确其诊断和分型。方法:采用先证者查证法调查和收集中国人牙本质发育异常家系,绘制系谱图,确定遗传方式,根据临床表现和X线征象特点对各家系受累个体进行表型分析。结果:共收集4个中国人牙本质发育异常家系,家系Ⅰ、Ⅱ、Ⅲ为常染色体显性遗传的Ⅱ型牙本质发育不全,家系Ⅳ先证者符合Ⅱ型牙本质发育不全诊断;临床表型在各家系及同一家系不同个体间存在异同。结论:独立发生于牙本质的各型遗传性牙本质发育异常存在共有表型,可作为同一类疾病研究。     

面横裂及附耳家系的临床表型及遗传学分析

目的：分析1组面横裂及附耳家系的临床表现及遗传学特征。材料和方法：我们随访到1组面横裂及附耳家系，家系内随访到共有5代发病，目前存活有4代，家系内共有成员60余人，进行了临床表型和遗传学的初步分析。结果：家系内有并发面横裂及附耳症状的病例5人，单纯附耳症状的病例7人，在遗传方式上属于常染色体显性遗传，从细胞遗传学水平对家系中成员进行染色体检测，未发现核型及染色体的异常。结论：家族性面横裂及附耳为常染色体显性遗传，核型及染色体检测未发现异常。     

Rieger综合征-附1例家系病例报告

目的：分析1例Rieger综合征的典型家系病例，对临床医师认识和诊断这一与口腔发育异常密切相关的罕见遗传病提供线索和信息。方法：对1例Rieger综合征患进行家系调查，对家系成员进行临床检查，修复治疗和表型分析。结果：临床诊断1例Rieger综合征病例家系，显示常染色体显性的遗传方式，该综合征可导致严重的上颌骨发育不足和多数恒牙先天缺失。结论：Rieger综合征是导致先天性牙齿缺失的重要遗传性疾病之一，由于修复治疗的需要，可能对口腔医师在这一疾病的发现和诊断中起到重要作用。     

先天缺指(趾)-外胚叶发育不良-唇/腭裂综合征的病例研究

目的：探讨先天缺指（趾）-外胚叶发育不良-唇／腭裂综合征（EEC）的临床表型和遗传学特点。方法：收集具有典型症状的EEC病例并进行家系问卷和口腔检查,观察各家系患者的临床表型和发病特点,分析可能的遗传方式,绘制系谱图。结果：研究收集的2个EEC病例均未追溯到明显家族遗传史,患者均表现出明显的双侧多个缺指（趾）,并指,唇／腭裂,家系2患者有毛发稀疏,指甲无光泽等明显外胚层发育不良表型,符合典型的EEC综合征。2名不同患者的严重程度存在明显差异。结论：收集的2个患者均属典型的散发EEC病例,临床的早期检查和正确诊断对后期治疗具有重要意义。     

遗传性牙龈纤维瘤病的临床研究

目的探讨遗传性牙龈纤维瘤病(hereditary gingival fibromatosis,HGF)的临床特征。方法回顾分析我院2001-2007年收治的3例HGF病例,对其遗传特点及相关的综合征,临床表现,X线片特征,组织病理,诊断分型及治疗预后进行分析。结果3例HGF患者1例为综合征型HGF,2例为非综合征型HGF,其遗传特性、发病年龄、临床表征各有所不同,但均具有典型全口牙龈增生及牙槽骨吸收。结论3例HGF不同个体表现不尽相同,具有一定的异质性。     

AXIN2基因的3个SNP位点与新疆维吾尔族先天缺牙的相关性

目的：探讨维吾尔族单纯型先天缺牙患者标本中AXIN2基因的突变位点。方法：收集维吾尔族非单纯型先天缺牙家系3个,采集家系患者颊黏膜拭子提取DNA,采用聚合酶链反应技术,对分段纯化的PCR产物进行DNA双向测序检测患者的DNA。结果：3个家系的单纯型先天缺牙临床表型符合常染色体显性遗传规律,患者出现不同数量的缺失牙或伴发锥形牙。测序后检测出AXIN2的3个可能的SNP位点。结论：AXIN2基因片段中某些编码基因的改变可能与维吾尔族单纯型先天缺牙有关。     

遗传性牙龈纤维瘤病家系永生化细胞库的建立及染色体初步分析

目的:建立遗传性牙龈纤维瘤病(HGF)家系外周血永生化淋巴细胞系,以永久保存现有患病家系特有的基因组资源,并探讨将其作为HGF发病机理研究的生物材料的可行性和可靠性.方法:在知情同意原则下,收集5个常染色体显性遗传HGF家系外周血样品,采用新鲜血法和冻存白细胞法,通过EB病毒(EBV)联合环孢霉素A(CyA)转化处理获得外周血永生化淋巴母细胞系,制备并分析细胞系的中期染色体片,检测建系前后的遗传稳定性.结果:成功建立5个HGF家系的永生化B淋巴母细胞系,所有建成细胞系冻存后复苏成功率达100%,转化前后的淋巴母细胞系G带显色核型分析无明显差异.结论:EB病毒转化构建的永生化淋巴细胞系遗传学特性稳定,可永久保存HGF家系资源,为今后在细胞和分子水平上开展HGF发病机理、诊断和治疗提供随时可取的实验材料奠定了基础.     

Hereditary gingival fibromatosis: Clinical and ultrastructural features of a new family

Objective: This article describes the diagnosis, clinical and microscopic (histopathology and ultrastructural) features and treatment of a new family with hereditary gingival fibromatosis (HGF) and highlights the importance of this genetic condition. Study Design: To characterize the pattern of inheritance and the clinical features, members of a new family with HGF were examined. The pedigree was reliably constructed including the four latest generations of family. Hematoxylin and eosin staining and ultrastructural analysis were performed with the gingival tissue. Results: Examination of the family pedigree revealed that the patient III-2 represent the index patient of this family (initial patient with a mutation), which was transmitted to her daughter through an autosomal dominant mode of inheritance. The affected patients showed a generalized gingival overgrowth. The patient was treated with surgical procedures of gingivectomy and gingivoplasty. The diagnosis was confirmed by histopathology examination that showed a well-structured epithelium with elongated and thin papillae inserted in fibrous connective tissue with increased amount of collagen. The ultrastructural aspects of the tissue show collagen fibrils exhibiting their typically repeating banding pattern with some fibrils displaying loops at their end. Moreover, it was possible to seen in some regions fibrillar component presenting tortuous aspects and loss of the alignment among them. Conclusions: This HGF frequently resulted in both esthetic and functional problems. The genetic pattern of this Brazilian family suggested a new mutation, which was later transmitted by an autosomal dominant trait. Key words:Gingival fibromatosis, genetic disease, pedigree, ultrastructure.     

Ultrastructural aspects of connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: The purpose of this study was to analyze the ultrastructure of gingival connective tissue from patients in one family affected by hereditary gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was performed with gingival tissue from 10 patients from a Brazilian family with 132 members. Fifty of 96 persons at risk for this disorder were affected, which is consistent with an autosomal dominant pattern of inheritance. RESULTS: The extracellular matrix showed flocculent material and collagen fibrils with structural abnormalities and variation in diameter. Increased numbers of oxytalan fibers were identified; however, elastic fibers were rare in the analyzed areas. CONCLUSIONS: The structural alterations found in HGF appear similar to those described in certain other heritable collagen disorders, suggesting that HGF should be included in the group of hereditary diseases in which connective tissue alterations have a distinct pattern, in contrast to reactive fibrotic gingival enlargements with no genetic component.     

Hereditary gingival fibromatosis: report of a five-generation family using cellular proliferation analysis

BACKGROUND: Hereditary gingival fibromatosis (HGF) is an uncommon condition characterized by an accumulation of extracellular matrix resulting in a fibrotic enlargement of the gingiva. The goal of this article is to describe one kindred affected with HGF and discuss the diagnosis, treatment, and control of the disease. The pattern of inheritance, histopathologic characteristics, and proliferative potential of epithelial and mesenchymal cells of HGF are also emphasized. METHODS: To characterize the pattern of inheritance and the clinical appearance of gingival overgrowth, 117 family members were examined. The recurrence risk was estimated by the use of a genetic analysis program. Immunohistochemistry against the proliferating cell nuclear antigen (PCNA) and pKi-67 was performed to assess cellular proliferation of normal gingiva (NG) and HGF cells. RESULTS: Examination of the family pedigree demonstrated an autosomal dominant trait of inheritance, and a sibling recurrence risk of 0.085 and an offspring recurrence risk of 0.078, indicating that HGF was a consequence of genetic alteration with low penetrance. Unaffected and affected members transmitted the disease to their offspring. The affected patients showed a generalized but mild gingival overgrowth. Surgical treatment consisted of a combination of gingivectomy and gingivoplasty. Histologic examination showed that the gingival lesions of all patients were quite similar, with increased amounts of collagen fiber bundles in the connective tissue. Immunohistochemistry revealed that the proliferative potential of epithelial cells was significantly higher in the HGF group compared to the NG group, whereas mesenchymal cells from both groups were negative for the proliferative markers. CONCLUSION: Our data demonstrated that, in the studied family, HGF is transmitted by an autosomal dominant pattern with incomplete disease penetrance, and although the gingival enlargement resulted from an excessive accumulation of collagen fibers, HGF is characterized by an increase in the proliferation rate of epithelial cells.     

Current concepts on gingival fibromatosis‐related syndromes

Gingival fibromatosis is a rare, benign, slowly‐growing fibrous overgrowth of the gingiva, with great genetic and clinical heterogeneity. Gingival fibromatosis/overgrowth can be inherited as an isolated trait (hereditary gingival fibromatosis) and/or as a component of a syndrome, or it can be drug induced. As a clinical manifestation of a syndrome, gingival fibromatosis is usually associated with generalized hypertrichosis, mental retardation, or epilepsy. Gingival fibromatosis and its related syndromes are mainly inherited in an autosomal‐dominant manner, but autosomal‐recessive inheritance has also been reported. Clinical syndromic presentation includes Zimmermann–Laband syndrome, Ramon syndrome, Rutherford syndrome, Cowden syndrome, Cross syndrome, Göhlich–Ratmann syndrome, Avani syndrome, and I‐cell disease. However, a phenotypic overlap has been suggested, as many combinations of their systemic manifestations have been reported. Treatment of choice is usually gingivectomy with gingivoplasty. Before any therapy, clinical practitioners must take into consideration the clinical course of a particular syndrome and every possible functional and esthetic disorder.     

Case reports of a new syndrome associating gingival fibromatosis and dental abnormalities in a consanguineous family

BACKGROUND: Gingival fibromatosis (GF) is characterized by fibrotic enlargement of the gingiva that can be inherited as an isolated trait (named hereditary gingival fibromatosis) or as a component of a syndrome. This article reports one kindred affected by a syndrome characterized by GF associated with dental abnormalities (DA) including generalized thin hypoplastic amelogenesis imperfecta (AI). METHODS: To characterize the pattern of inheritance and the clinical features, 70 family members were examined. Hematoxylin and eosin staining, immunohistochemistry, and scanning electronic microscopy (SEM) were performed to identify the alterations on gingiva, teeth, and dental follicles. RESULTS: Examination of the family pedigree demonstrated multiple consanguineous first-cousin marriages and an autosomal recessive trait of inheritance. Four members demonstrated mild GF in association with DA, including generalized thin hypoplastic AI, intrapulpal calcifications, delay of tooth eruption, and pericoronal radiolucencies involving unerupted teeth. One of those four patients also had mental retardation (MR). MR as an isolated feature was observed in six members, whereas isolated GF was found in one individual. A combination of gingivectomy and gingivoplasty followed by regular dental procedures were performed in these patients. Histologic examination of the gingival enlargement revealed a dense connective tissue containing myofibroblasts, islands of odontogenic epithelium, and calcified psammomatous deposits, which resembled cementicle-like structures by SEM. Pericoronal lesions also showed calcified psammomatous deposits in association with islands of odontogenic epithelium. Enamel ultrastructure analysis revealed normal surface alternating with irregular and porous areas. CONCLUSION: To the best of our knowledge, these cases represent a new syndrome within the spectrum of those including GF.     

Familial gingival fibromatosis; no correlation with HLA-antigen A family study

Familial gingival fibromatosis is generally reported to be inherited as an autosomal dominant trait. We investigated 2 families with few siblings affected with gingival fibromatosis. No linkage between HLA antigen and the phenomenon was found. These results support the idea of the autosomal dominant nature of familial gingival fibromatosis.     

Nonsyndromic hereditary gingival fibromatosis: Characterization of a family and review of genetic etiology

Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.     

Focus of epithelial dysplasia arising in hereditary gingival fibromatosis

The gingiva of a 32-year-old black male was biopsied for evidence of vasculitis, but instead an area of epithelial dysplasia was found. Further investigation revealed that the patient and several members of his family had hereditary gingival fibromatosis. Treatment included four quadrants of gingivectomy plus inverse bevel incisions for trimming those areas which were too thick for simple gingivectomy. Histopathologic examination of the excised tissues supported the diagnosis of gingival fibromatosis, but no other areas of epithelial dysplasia were seen. To our knowledge, this is the only reported instance of a premalignancy or malignancy arising in gingival fibromatosis, and thus there is no reason to regard the gingival disorder as predisposing to carcinoma. However, the pedigree reported here supports a previous suggestion that hereditary gingival fibromatosis is not as rare among blacks as the literature has indicated.