Van der Woude syndrome: dentofacial features and implications for clinical practice

Background:  Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis.
Methods:  A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort.
Results:  The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals.
Conclusions:  Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.     

Linkage analysis of candidate regions in Swedish nonsyndromic cleft lip with or without cleft palate families.

OBJECTIVE: To analyze linkage of five candidate regions for nonsyndromic cleft lip with or without palate (CLP) on chromosome 2p13, 4q, 6p23, and 19q13; in addition chromosome 1q32, the locus for van der Woude syndrome, on Swedish CLP families. DESIGN: Three to five linked microsatellite markers were selected from each candidate region. Polymerase chain reaction (PCR) with fluorescent-labeled microsatellite markers was performed on DNA samples from the participating families. Electrophoresis of the PCR products was performed on a laser-fluorescent DNA sequencer. The genotype data were analyzed with multipoint linkage analysis. Modes of inheritance tested included two autosomal dominant, an autosomal recessive, and a nonparametric model. Multipoint logarithm of odds (LOD) scores were also calculated by assuming genetic heterogeneity. PARTICIPANTS: Nineteen Swedish multigenerational families with at least two first-degree relatives affected with CLP. Greater than 50% of the families studied show vertical transmission of the clefting phenotype and both inter- and intrafamilial variability were noted. RESULTS: Cumulative multipoint LOD scores for the whole group of families calculated under autosomal dominant modes of inheritance were negative in all regions and less than -2 except chromosome 6p23. LOD scores calculated under recessive inheritance and the nonparametric model were inconclusive. There was no significant evidence of genetic heterogeneity among the sample group. CONCLUSIONS: The group of Swedish CLP families did not demonstrate significant linkage to any of the five candidate regions examined. This might suggest a new but yet unknown CLP locus or loci in this family group. However, because linkage could not be excluded in some individual families, they should still be tested with candidate genes from these regions.     

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。     

Chromosome 17: gene mapping studies of cleft lip with or without cleft palate in Chinese families.

OBJECTIVE: Involvement of loci on chromosome 17, including retinoic acid receptor alpha (RARA) in nonsyndromic oral clefts has been reported in Caucasian populations, although never investigated in Asian populations. The purpose of the present study was to investigate several loci on chromosome 17, including RARA, in Chinese families. PARTICIPANTS: Thirty-six multiplex families (310 individuals), ascertained through nonsyndromic cleft lip with or without cleft palate surgical probands from hospitals in Shanghai, China, participated in the present study. There were 23 families whose probands had cleft lip and cleft palate (CLP) and 13 with cleft lip alone (CL). RESULTS: Seventeen markers, spanning chromosome 17 and about 10 cM apart were assessed. Logarithm of odds ratio (LOD) scores (two point and multipoint), model-free linkage analyses, and allelic association tests (transmission/disequilibrium, Fisher's exact tests, and chi-square) were performed on the total family sample, families with CLP probands (CLP subgroup), and families with CL probands (CL subgroup). LOD scores from the two-point analyses were inconclusive. Multipoint analyses rejected linkage except for a few regions in the CL subgroup. However, positive results were found using the model-free linkage and association methods (p < .05). The markers with positive results varied across the CL and CLP subgroups. However, the RARA region and loci nearby yielded consistently positive results. CONCLUSION: Genetic variation within the RARA locus or nearby appears to be involved in the pathogenesis of nonsyndromic oral clefts in this population. Furthermore, based on the differing pattern of results in the CL versus CLP subgroups, it appears that the formation of CL and CLP is because of either differing alleles at the same genetic locus or different but related (and/or linked) genes that modify the severity and expression of oral clefting.     

Linkage analysis between BCL3 and nearby genes on 19q13.2 and non-syndromic cleft lip with or without cleft palate in multigenerational Japanese families

OBJECTIVE: To investigate the linkage between candidate genes on chromosome 19 and cleft lip with or without cleft palate in Japanese using a parametric method. MATERIALS AND METHODS: After informed consent was obtained, blood samples were drawn from 90 individuals in 14 families, 30 of whom were affected, and genomic DNAs were extracted. PCR-amplified products using four microsatellite markers, D19S178, BCL3, APOC2[007/008] and APOC2[AC1/AC2] located in 19q13.2, were separated by 8% polyacrylamide gel electrophoresis. Linkage analysis was carried out using the MLINK and LINKMAP programs, and logarithm of odds (LOD) scores were calculated for each family. RESULTS: Before undertaking linkage analysis, we analyzed 74 healthy Japanese subjects and found racial differences in that the observed number of alleles and their heterozygosity were lower in Japanese than in Caucasians, and that both populations tended to show a different allele distribution. In 14 families, two-point maximum LOD score (Zmax) for BCL3 was 0.341 and multi-point Zmax was less than -2 excluding linkage. But in 9 families with left and bilateral CL/P, two-point Zmax for APOC2[AC1/AC2] was 1.701 and multi-point Zmax at APOC2 locus was 1.909. CONCLUSION: The LOD score was relatively high but provided no evidence of linkage for CL/P to BCL3 and nearby genes in Japanese subjects.     

Popliteal pterygium syndrome in a Swedish family-clinical findings and genetic analysis with the van der Woude syndrome locus at 1q32-q41

The present study describes a Swedish family in which the mother and her son were affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both individuals had bilateral complete cleft lip and palate, oral synechiae, paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin overgrowth on the great toes. The son also presented with soft tissue syndactyly of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above clinical features were diagnostic for PPS. Chromosomal abnormalities were not revealed in either case by cytogenetic analyses. A test for microdeletion in the VWS region at 1q32-q41 was performed in the family using 5 polymorphic microsatellite markers from the region. The affected son was found to be heterozygous for all 5 markers, suggesting that microdeletion at the VWS region was unlikely. The VWS locus, however, was not excluded by haplotype analysis of the family.     

Popliteal pterygium syndrome in a Swedish family--clinical findings and genetic analysis with the van der Woude syndrome locus at 1q32-q41

The present study describes a Swedish family in which the mother and her son were affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both individuals had bilateral complete cleft lip and palate, oral synechiae, paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin overgrowth on the great toes. The son also presented with soft tissue syndactyly of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above clinical features were diagnostic for PPS. Chromosomal abnormalities were not revealed in either case by cytogenetic analyses. A test for microdeletion in the VWS region at 1q32-q41 was performed in the family using 5 polymorphic microsatellite markers from the region. The affected son was found to be heterozygous for all 5 markers, suggesting that microdeletion at the VWS region was unlikely. The VWS locus, however, was not excluded by haplotype analysis of the family.     

Two missense mutations in the IRF6 gene in two Japanese families with Van der Woude syndrome

Van der Woude syndrome (VWS) is a common autosomal dominant disorder with cleft lip and/or palate and lower lip pits. Its prevalence is estimated to be 1/33,600 in the Finnish Population, and 1/47,813 in the Japanese. We performed mutation analysis of the IRF6 gene by direct sequencing in 2 unrelated Japanese families that consist of a total of 3 affected members with cleft lip and palate associated with lower lip pits. Consequently, we found novel base substitutions, 25C>T, in IRF6-exon 3 in a boy, his mother, and his phenotypically normal maternal grandmother in one of the families. A known mutation, 250C>T, was identified in exon 4 of a girl and her unaffected father in the other family. The same mutations were never observed among 190 healthy Japanese. The results indicate incomplete penetrance and variable expressivity in the families. Because 25C>T and 250C>T predict to lead to R9W and R84C substitutions, respectively, at the most conserved DNA binding domain of IRF6, and because arginine at positions 9 and 84 is highly conserved among IRFs, the 2 mutations may lead to abolish the DNA binding activity in the developing craniofacial region. To our knowledge, this is the first report of IRF6 mutations observed in Japanese VWS patients.     

Nonsyndromic cleft lip with or without cleft palate in China: assessment of candidate regions.

OBJECTIVE: Although Asians have the highest birth prevalence of oral-facial clefts, the majority of gene mapping studies of cleft lip with or without cleft palate (CL/P) have been in European or American Caucasians. Therefore, the objective of this study of Chinese families was to evaluate linkage and association between CL/P and 10 genetic markers in five chromosomal regions that have shown positive results in Caucasians. SETTING: Families were ascertained through nonsyndromic CL/P surgical probands from hospitals throughout Shanghai, China. PARTICIPANTS: Study participants included 671 individuals from 60 families with two or more members affected with oral-facial clefts. Of the 671 total individuals, 145 were affected. RESULTS: Ten markers from chromosomes 2, 4, 6, 17, and 19 were assessed (TGFA, MSX1, D4S194, D4S175, F13A1, GATA185H, D17S250, D17S579, D19S49, APOC2). LOD scores were calculated between each of the 10 markers and CL/P as well as model-free statistics of linkage (SimIBD) and association (TDT). None of the markers showed significantly positive LOD scores with CL/P. A significantly positive result (p =.01) was seen using SimIBD for APOC2 on chromosome 19, and a positive TDT result (p =.004) was obtained for D19S49, near APOC2. CONCLUSIONS: This is the first gene mapping study of CL/P in China. These results indicate that most of the genetic regions with positive results in Caucasian families may not be involved in CL/P found in China, although there is some positive evidence for the candidate region on chromosome 19.     

No evidence for linkage and association between 4q microsatellite markers and nonsyndromic cleft lip and palate in chilean case-parents trios.

OBJECTIVE: Nonsyndromic cleft lip/palate (NSCLP) has the characteristics of a complex genetic trait. Linkage and association studies have suggested that one or more clefting loci may be located on chromosome 4q. The goal of this study was to evaluate the possible linkage and association due to linkage disequilibrium between five microsatellite markers located on 4q28 to 4q33 and NSCLP, using the case-parent trio design. SUBJECTS AND METHODS: A total of 56 Chilean families (32 simplex and 24 multiplex) were recruited. Microsatellite markers were analyzed using polymerase chain reaction with fluorescent-labeled forward primers, followed by electrophoresis on a laser-fluorescent sequencer. Case-parents trios were ascertained to assess linkage and linkage disequilibrium through a multistage procedure. Transmission disequilibrium tests for multiple alleles were carried out to assess the statistical significance of 4q28 to 4q33 microsatellite markers. RESULTS: Only weak evidence for linkage was obtained for the FGA marker (asymptotic uncorrected p value = .08 and empirical p value = .05). Only the FGA and UCP1 markers were selected for association analysis in trios, with unrelated cases achieving a nearly significant result for the UCP1 marker (asymptotic uncorrected p value = .07 and empirical p value = .19). CONCLUSION: Though the FGA and UCP1 markers showed nearly significant p values for linkage and association, respectively, the results of the present study provided insufficient evidence of the existence of a major susceptibility locus in the 4q region that was analyzed in the present study.     

1433例唇腭裂患者临床资料分析

目的：分析先天性唇腭裂的发病情况及特点,为唇腭裂的预防提供临床资料。方法：对1433例先天性唇腭裂患者进行回顾性临床分析。结果：本组病例中,唇裂390例,唇裂伴腭裂794例,单纯腭裂249例;男性明显多于女性（2.35：1）,但在不完全性腭裂中,女性多于男性（1：0.87）;在单侧唇裂伴或不伴腭裂及完全腭裂中,左侧明显多于右侧（3.58：1）;有家族遗传史的病例占总病例的6.35%;母亲妊娠初期经历危险因素316例,占22.05%;85.97%的患者来自农村;唇腭裂伴发其他畸型者42例,占2.93%。结论：多基因遗传与胚胎发育早期的环境因素是唇腭裂发病的重要因素。     

Classification of oral clefts by affection site and laterality: a genotype-phenotype correlation study

Objectives – The aim of this study was to classify the phenotypes found in a series of patients with non‐syndromic cleft lip (CL) with or without cleft palate (CP) and isolated cleft palate. Additionally, the frequency distribution of cases belonging to families linked to markers on chromosomes 6 and 2 within these phenotypic patterns were estimated. Design – A retrospective examination of all the available affected cases collected in Italy. Setting and Sample Population – Ninety‐seven affected subjects aged 5–18 years belonging to 38 families were considered. Patterns were identified by variance of the cleft (lip, primary palate, secondary palate) and stratified according to the side of occurrence (right, left, or bilateral). Latent class analysis was used as main statistical tool for carrying out the results. Results – Three homogenous classes were identified (P < 0.0001) by means of latent class analysis. Individuals were assigned to the most suited class. All three variables (lip, primary and secondary cleft palate) generated a specific class. Optimal findings were reported in cases having `any isolated cleft lip' (class 1); `secondary CP with or without bilateral/right primary cleft palate + bilateral/right cleft lip' (class 2); and `left primary cleft palate + left/bilateral cleft lip with or without secondary CP' (class 3). Correspondence to the evidence of linkage to chromosome 6 showed that 9 of 10 cases presenting with `right primary CP + right CL with secondary cleft palate' (class 2) belonged to a linked family. The same combination, but occurring on the left side (class 3), revealed that only three of nine cases belong to families linked to chromosome 6 (P‐value=0.02). The two patterns (right and left) never occurred in the same family. Three reliable groups were identified based on laterality and the presence of a cleft. A single right sided pattern displayed a statistically different distribution of linkage to chromosome 6 when compared with the homologous left side. Conclusion – Non‐syndromic CL with/without CP can be classified according to laterality that can be under genetic control.     

Novel IRF6 mutations in Chinese patients with Van der Woude syndrome

Van der Woude syndrome (VWS) (OMIM 119300) is a dominantly inherited, developmental disorder that is characterized by pits and/or sinuses of the lower lip and a cleft lip and/or cleft palate. Mutations in the interferon regulatory factor 6 gene (IRF6) have been recently identified in patients with VWS, with more than 60 mutations reported. However, the VWS phenotype, IRF6 mutation genotypes, and their interrelationships in Chinese VWS patients have not been studied. Here, we report 11 Chinese families with variable clinical phenotypes of VWS and identified mutations in all patients. Of the 11 mutations, 8 appeared to be novel: CC5.6GT, T342A, 566delA, C748T, C756A, C989A, C1209G, and 1316delT. Seven mutations caused a change or loss of the IRF6 domain. The marked phenotypic variation may be caused by the action of certain modifier genes on IRF6 function.     

一个范德伍德综合征家系的IRF6基因突变检测

目的:对收集的1个湖北Van der Woude综合征(VWS)家系进行临床和遗传特点分析,并进行IRF6基因的突变检测。方法:通过先证者及现场家系调查、临床检查和系谱分析收集VWS家系。在IRF6基因的外显子-内含子接头及9个外显子编码区分别设计引物,经聚合酶链式反应扩增并纯化后直接测序。结果:收集的VWS家系符合常染色体显性遗传特征,家系受累患者共3名(1名男性和2名女性),患者表现为典型的下唇瘘管或凹陷,且合并有唇腭裂和先天缺牙。患者表型在同一家系内有明显差异,且呈逐代加重趋势。在所有患者IRF6基因第412位密码子发现与表型一致的CGA>TGA(c.1234C>T)改变,经查证为一个已知的无义突变。结论:该VWS家系疾病表现度极不一致,是由IRF6基因的1个已知无义突变导致,IRF6是参与颌面部发育的重要基因。     

1967例江西地区先天性唇腭裂患者家族史病例对照研究

目的:探讨家族遗传对非综合征型唇腭裂患者表现性状的影响.方法:收集2002 ～ 2014年于南昌大学附属口腔医院诊治的非综合征型唇腭裂患者病历1 967份,分为家族史组和散发组,就2组患者各表现性状进行病例对照研究.结果:164例(8.34％)患者具有家族史.单纯性唇裂(CLO)、唇裂合并牙槽裂(CLA)、唇裂合并腭裂(CLP)和单纯性腭裂(CPO)各家族史阳性率为:8.11％、8.54％、9.65％和6.19％.相对于散发组,家族史组中发生CPO的风险是CLO、CLA和CLP的0.66倍(P=0.036,OR =0.66,95％C1 0.44-0.98).家族史组中CLP的男性和女性患者在唇腭裂发生左右侧具有统计学差异(P＜0.001).家族史组和散发组2组在患者出生体重、父母生育年龄和临床表现无统计学差异.结论:家族遗传可能对唇腭裂的发生类型、部位和性别产生影响.     

Familial non-syndromic cleft lip and palate--analysis of the IRF6 gene and clinical phenotypes

The aim of this study was to characterize Swedish families with non-syndromic cleft lip and/or palate (NSCL/P) for mutations or other sequence variants in the interferon regulatory factor 6 (IRF6) gene, as well as to describe their cleft phenotypes and hypodontia. Seventeen Swedish families with at least two family members with NSCL/P were identified and clinically evaluated. Extracted DNA from blood samples was used for IRF6 mutation screening. Exonic fragments of the IRF6 gene were sequenced and chromatograms were inspected. Statistical analysis was undertaken with marker- and haplotype association tests. No disease-associated IRF6 mutation could be determined in the families analyzed. One new and seven known single nucleotide polymorphisms (SNPs) were detected. The A allele of SNP rs861019 in exon 2 and the G allele of SNP rs7552506 in intron 3 showed association with cleft lip and palate (CLP; odds ratios of 3.1 and 5.45, respectively). Hypodontia was observed more commonly in individuals affected with CL/P as compared with family members without a cleft (P < 0.01). The hypodontia most often affected the cleft area, possibly representing a secondary effect. The distribution of cleft phenotypes in 15 of the 17 families with NSCL/P differed from the mixed cleft types seen in Van der Woude syndrome (VWS), in that CLP did not occur together with an isolated cleft palate within the same family. It was concluded that mutations of the IRF6 gene are not a common cause for cleft predisposition in Swedish NSCL/P families.     

Contributions of PTCH gene variants to isolated cleft lip and palate.

OBJECTIVE: Mutations in patched (PTCH) cause the nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may present with developmental anomalies, including rib and craniofacial abnormalities, and predisposes to several tumor types, including basal cell carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with nevoid basal cell carcinoma syndrome. Because there might be specific sequence alterations in PTCH that limit expression to orofacial clefting, a genetic study of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to have nevoid basal cell carcinoma syndrome. RESULTS: Seven new normal variants spread along the entire gene and three missense mutations were found among cases with cleft lip and/or palate. One of these variants (P295S) was not found in any of 1188 control samples. A second variant was found in a case and also in 1 of 1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5 of 1104 controls and is likely a rare normal variant. Linkage and linkage desequilibrium also was assessed using normal variants in and adjacent to the PTCH gene in 220 families (1776 individuals), each with two or more individuals with isolated clefting. Although no statistically significant evidence of linkage (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of significant transmission distortion for one haplotype of two single nucleotide polymorphisms located within the PTCH gene (p = .08). CONCLUSION: Missense mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as yet unidentified variant near PTCH may act as a modifier of cleft lip and/or palate.     

Clinical and genetic features of Van der Woude syndrome in two large families in Brazil.

OBJECTIVE: This report describes the clinical and genetic features of two large and unrelated families with Van der Woude syndrome in Brazil, emphasizing the range of anomalies found within and between the families. PATIENTS: Family 1 included 54 descendants spanning five generations, with 12 (22.23%) individuals manifesting Van der Woude syndrome. In family 2, examinations comprised 17 descendants distributed over four generations, and 8 (47.06%) people presented features of Van der Woude syndrome. RESULTS: In family 1, the first two generations were not affected, but the other three generations had affected members showing a unique association of lip pits and cleft lip/palate with equilibrated gender distribution. In family 2, all generations were affected, and the clinical expression of disease was heterogeneous, including members with isolated clefts, isolated lip pits, and association of cleft lip/palate with lip pits. In both families, affected members transmitted their traits to descendants in an autosomal dominant mode of inheritance with apparent low penetrance in family 1, but high penetrance in family 2. Patients were treated surgically by cheiloplasty and/or palatoplasty with satisfactory results. CONCLUSIONS: Van der Woude syndrome was transmitted by an autosomal dominant pattern with variable expressivity and penetrance and equilibrated gender distribution. Physicians should be aware of the variety of malformations that can be associated with Van der Woude syndrome. Genetic counseling in Van der Woude syndrome affected families is important, because a high percentage of descendants can have some kind of clefting.     

2447例唇腭裂患者的临床资料分析

目的　了解先天性唇腭裂的患病状况及特点 ,寻找与唇腭裂发生有关的影响因素 ,为唇腭裂的预防与治疗提供依据。方法　对 1989～ 1998,10年间在原华西医科大学口腔医院颌面外科手术治疗的 2 4 4 7病例进行回顾性临床统计学分析。结果　在本组病例中 ,唇裂 6 4 8(2 6 5 % )、唇腭裂 996 (40 7% )、单纯腭裂 80 3(32 8% )。唇裂伴或不伴腭裂中 ,男多于女 (2 .14∶1) ,单纯腭裂女多于男 (0 77∶1)。单侧唇腭裂明显多于双侧 ,两者之比为 4 84∶1,其中左侧者多于右侧者 ,两者之比为 2 14∶1。有遗传史的病例占病例总数的 7 4 % ,其中唇裂伴或不伴腭裂有遗传史者占唇裂伴或不伴腭裂患者的 8 2 % ,单纯腭裂有遗传史者占单纯腭裂患者的 6 5 %。母亲怀孕前 3月经历危险因素有 95 4例 ,占 39 0 % ,其中唇裂伴或不伴腭裂者 70 0例 ,占唇裂伴或不伴腭裂患者数的 4 2 6 % ,单纯腭裂2 5 4例 ,占单纯腭裂的 31 6 %。A型和O型血患者比例高于正常人群比例 ,而B型血者比例低于正常人群比例 ,单纯唇裂出生于 4～ 6月者人数小于其他季度 ,而单纯腭裂出生于 7～ 9月者人数少于其他季度 ;19例双生子中 ,均为其中之一发病 ,无同时发病者。唇腭裂伴发畸形者共 4 1例 ,占总病例数的 1 7%。结论　本资料提示唇腭裂的发生可?     

1320例唇腭裂患者临床统计分析

目的:了解唇腭裂的最新流行病学情况,寻找与唇腭裂发生相关的可能因素,为唇腭裂病因研究及预防提供临床资料.方法:对我院自2001年1月至2006年12月收治的1320例唇腭裂患者进行回顾性临床统计分析.结果:本组病例中,男性920例(69.70%),女性400例(30.30%);唇裂410(31.06%)、唇裂伴腭裂782例(59.24%)、单纯腭裂128例(9.70%) ;全部病例中合并牙槽突裂895例,占67.80%;单侧唇裂伴或不伴腭裂明显多于双侧者,两者之比为3.26:1,其中左侧多于右侧(1.71:1);有家族遗传史的病例占总病例的4.47%,其中唇裂伴或不伴腭裂有遗传史者占唇裂伴或不伴腭裂病例总数的3.86%,单纯腭裂有遗传史者占单纯腭裂病例总数的10.16%;唇腭裂患者母亲孕3个月经历危险因素者共267例,占唇腭裂总数的20.23%,其中唇裂伴或不伴腭裂患者224例,占唇裂伴或不伴腭裂患者总数的18.79%,单纯腭裂患者43例,占单纯腭裂患者总数的33.59%;所有患者中出生于7～9月者均少于其它其它季度.结论:唇腭裂发病以唇裂合并腭裂居多,且以单侧发病多于双侧,男性发病多于女性发病.多基因遗传和胚胎所处的环境因素是唇腭裂的重要病因.