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Popliteal pterygium syndrome (PPS) is a rare inherited disorder involving the face, limbs, and genitalia. The most prominent and handicapping deformity associated with this syndrome is Popliteal pterygium. Popliteal pterygium is a contracture band that extends from ischial tuberosity to calcaneum. It is a dense fibrous band difficult to correct surgically. We report a case of PPS with her two other family members diagnosed with Van der Woude syndrome. Single-stage surgical release is ineffective due to shortened neurovascular and surrounding soft tissues. Multimodality treatment with surgical release and motivated parents may help these children to rehabilitate. [ABSTRACT FROM AUTHOR]

Objective: Van der Woude syndrome is characterized by the concurrence of cleft lip and palate with lower lip fistulas. During fistula resection, care must be taken to maintain the function of the orbicularis oris and restore the normal shape of the lips. Several reports have documented various resection methods; however, the most appropriate surgical resection is controversial. In this report, lower lip fistulas were resected using an inverted‐T surgical design. Methods: Of the six patients with Van der Woude syndrome who underwent resection of the lower lip fistula in our department between January 2007 and December 2015, three patients who underwent inverted‐T lip reduction were included. The postoperative position‐dependent morphology of the fistulas was examined. Results: Five years postoperatively, no complications such as postoperative infections, mucous retention cyst formation, a dysmorphic appearance of the lip, or fistula recurrence were observed. Moreover, a stable wound morphology was evident. Conclusions: The inverted‐T lip reduction seems to be promising technique for the excision of lower lip fistulas in patients with Van der Woude syndrome, yielding good results. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to analyze the clinical characteristics of patients with Van der Woude syndrome (VWS) and to detect variations in each patient. Finally, the combination of genotype and phenotype can make a clear diagnosis of VWS patients with different phenotype penetrance. Methods: Five Chinese VWS pedigree were enrolled. Whole exome sequencing of the proband was performed, and the potential pathogenic variation was further verified by Sanger sequencing in the patient and their parents. The human mutant IRF6 coding sequence was generated from the human full-length IRF6 plasmid by site-directed mutagenesis and cloned into the GV658 vector, RT-qPCR and Western blot were used to detect the expression of IRF6. Results: We found one de novo nonsense variation (p. Gln118Ter) and three novel missense variations (p. Gly301Glu, p. Gly267Ala, and p. Glu404Gly) co-segregated with VWS. RT-qPCR analysis revealed that p. Glu404Gly significantly reduced the expression level of IRF6 mRNA. Western blot of cell lysates confirmed that IRF6 p. Glu404Gly abundance levels were lower than those for IRF6 wild type. Conclusions: This discovery of the novel variation (IRF6 p. Glu404Gly) expands the spectrum of known variations in VWS in Chinese humans. Genetic results combined with clinical phenotypes and differential diagnosis points from other diseases can make a definitive diagnosis and provide genetic counseling for families. [ABSTRACT FROM AUTHOR]

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation-c.748C>T:p.R250X-in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6-p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation's role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFβ2-AS1 expression. The findings highlight the mutation's influence on TGFβ2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS's molecular underpinnings and might inform future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background Virtual wards (VWs) deliver multidisciplinary care at home to people with frailty who are at high risk of a crisis or in crisis, aiming to mitigate the risk of acute hospital admission. Different VW models exist, and evidence of effectiveness is inconsistent. Aim We conducted a rapid realist review to identify different VW models and to develop explanations for how and why VWs could deliver effective frailty management. Methods We searched published and grey literature to identify evidence on multidisciplinary VWs. Information on how and why VWs might 'work' was extracted and synthesised into context-mechanism-outcome configurations with input from clinicians and patient/public contributors. Results We included 17 peer-reviewed and 11 grey literature documents. VWs could be short-term and acute (1–21 days), or longer-term and preventative (typically 3–7 months). Effective VW operation requires common standards agreements, information sharing processes, an appropriate multidisciplinary team that plans patient care remotely, and good co-ordination. VWs may enable delivery of frailty interventions through appropriate selection of patients, comprehensive assessment including medication review, integrated case management and proactive care. Important components for patients and caregivers are good communication with the VW, their experience of care at home, and feeling involved, safe and empowered to manage their condition. Conclusions Insights gained from this review could inform implementation or evaluation of VWs for frailty. A combination of acute and longer-term VWs may be needed within a whole system approach. Proactive care is recommended to avoid frailty-related crises. [ABSTRACT FROM AUTHOR]

Background: To date, there are over 320 variants identified in the IRF6 gene that cause Van der Woude syndrome or popliteal pterygium syndrome. We sequenced this gene in a South African orofacial cleft cohort to identify the causal IRF6 variants in our population. Method: Saliva samples from 100 patients with syndromic and non‐syndromic CL ± P were collected. Patients were recruited from the cleft clinics at two public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu‐Natal Children's Hospital (KZNCH). We prospectively sequenced the exons of IRF6 in 100 orofacial cleft cases, and where possible, we also sequenced the parents of the individuals to determine the segregation pattern. Results: Two variants were identified; one novel (p.Cys114Tyr) and one known (p.Arg84His) missense variant in IRF6 gene were identified. The patient with the p.Cys114Tyr variant was non‐syndromic with no clinical VWS phenotype expected of individuals with IRF6 coding variants, and the patient with the p.Arg84His had phenotypic features of popliteal pterygium syndrome. The p.Arg84His variant segregated in the family, with the father also being affected. Conclusions: This study provides evidence that IRF6 variants are found in the South African population. Genetic counselling is essential for affected families, particularly in the absence of a known clinical phenotype since it helps with the plans for future pregnancies. [ABSTRACT FROM AUTHOR]

Aim: To describe the particular craniofacial characteristics of Van der Woude syndrome(VWS) patients compared to patients with a non‐syndromic cleft (CG1) and to a malocclusive healthy population (CG2). Material and methods: Retrospective case‐control study. A sample of 110 matched‐patients was recruited (VWS (n = 7), CG1 (n = 49), CG2 (n = 49)). Subsequently, 37 radiometric variables were analysed and the dental‐skeletal ages were determined. The intra/inter‐observer method errors were quantified. Descriptive statistics were computed, and different inferential analysis tests were used depending on the normality of the data (Chi‐square test, Fisher's exact test, paired Student's T‐test, Mann–Whitney U test) (p‐value < 0.05). Pairwise comparisons were corrected by Bonferroni's criteria. Results: VW‐patients presented specific craniofacial characteristics and morphology. A marked tendency to the vertical growth pattern was found in VW‐patients compared to CG1‐CG2 (p < 0.001); at the sagittal level, skeletal class II caused by mandibular retrognathism, with a greatly increased ANB angle compared to CG1 (p = 0.042). Dental analysis showed that the lower incisor was more retruded and retroclined (p < 0.05 in all cases) and the interincisal angulation was increased (p < 0.001 (CG2)). At the profile level, an open nasolabial angle (p = 0.040; CG1) and a more protruding lower lip with respect to the Sn‐Pg plane (p = 0.040 (CG1); p = 0.044 (CG2)) were observed. Conclusions: VW‐patients present particular characteristics in the facial skeletal structures. There is a critical necessity to increase the evidence regarding specific clinical features and orofacial pathology of rare diseases such as VWS, which will help to these minorities to gain access in the future to a better quality of care with precise treatment and diagnostic necessities. [ABSTRACT FROM AUTHOR]

Abstract Background To date, there are over 320 variants identified in the IRF6 gene that cause Van der Woude syndrome or popliteal pterygium syndrome. We sequenced this gene in a South African orofacial cleft cohort to identify the causal IRF6 variants in our population. Method Saliva samples from 100 patients with syndromic and non‐syndromic CL ± P were collected. Patients were recruited from the cleft clinics at two public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu‐Natal Children's Hospital (KZNCH). We prospectively sequenced the exons of IRF6 in 100 orofacial cleft cases, and where possible, we also sequenced the parents of the individuals to determine the segregation pattern. Results Two variants were identified; one novel (p.Cys114Tyr) and one known (p.Arg84His) missense variant in IRF6 gene were identified. The patient with the p.Cys114Tyr variant was non‐syndromic with no clinical VWS phenotype expected of individuals with IRF6 coding variants, and the patient with the p.Arg84His had phenotypic features of popliteal pterygium syndrome. The p.Arg84His variant segregated in the family, with the father also being affected. Conclusions This study provides evidence that IRF6 variants are found in the South African population. Genetic counselling is essential for affected families, particularly in the absence of a known clinical phenotype since it helps with the plans for future pregnancies.

Although the aetiology of non-syndromic orofacial clefts (nsOFCs) is usually multifactorial, syndromic OFCs (syOFCs) are often caused by single mutations in known genes. Some syndromes, e.g., Van der Woude syndrome (VWS1; VWS2) and X-linked cleft palate with or without ankyloglossia (CPX), show only minor clinical signs in addition to OFC and are sometimes difficult to differentiate from nsOFCs. We recruited 34 Slovenian multi-case families with apparent nsOFCs (isolated OFCs or OFCs with minor additional facial signs). First, we examined IRF6, GRHL3, and TBX22 by Sanger or whole exome sequencing to identify VWS and CPX families. Next, we examined 72 additional nsOFC genes in the remaining families. Variant validation and co-segregation analysis were performed for each identified variant using Sanger sequencing, real-time quantitative PCR and microarray-based comparative genomic hybridization. We identified six disease-causing variants (three novel) in IRF6, GRHL3, and TBX22 in 21% of families with apparent nsOFCs, suggesting that our sequencing approach is useful for distinguishing syOFCs from nsOFCs. The novel variants, a frameshift variant in exon 7 of IRF6, a splice-altering variant in GRHL3, and a deletion of the coding exons of TBX22, indicate VWS1, VWS2, and CPX, respectively. We also identified five rare variants in nsOFC genes in families without VWS or CPX, but they could not be conclusively linked to nsOFC. [ABSTRACT FROM AUTHOR]

Van der Woude syndrome (VWS) is a rare syndrome of genetic etiology, commonly occasioned by mutations in the IRF6 gene and that causes disorders in craniofacial development. VWS is characterized by the presence of paramedian fistulas in the lower lip and cleft lip and / or cleft palate. Although some dental phenotypes have been reported in this syndrome, multiple and rare hypodontias were not described. Through this case report, we present a case of Van der Woude Syndrome (VWS) with rare and multiple hypodontia in which clinical data and radiographic exams were evaluated. The patient presented hypodontia of eight permanent teeth (lateral incisors, second premolars and second molars). So, when the dentist recognizes multiple and/or rare hypodontias, for an accurate diagnosis, detailed examination of the lower lip is indicated, as well as a survey of the family history and referral for genetic counseling, since the syndrome presents high penetrance. The patient is expected to be rehabilitated to have a good quality of life. Rehabilitation in these cases requires alveolar bone graft, orthodontics and prosthesis to replace missing teeth. [ABSTRACT FROM AUTHOR]

IntroductionVan der Woude syndrome (VWS) is an autosomal dominant disorder responsible for 2% of all syndromic orofacial clefts (OFCs), with IRF6 being the primary causal gene (70%). Cases may present with lip pits and either cleft lip, cleft lip with cleft palate, or cleft palate, with marked phenotypic discordance even among individuals carrying the same mutation. This suggests that genetic or epigenetic modifiers may play additional roles in the syndrome's etiology and variability in expression. We report the first DNA methylation profiling of two pairs of monozygotic twins with VWS. Our goal is to explore epigenetic contributions to VWS etiology and variable phenotypic expressivity by comparing DNAm profiles in both twin pairs. While the mutations that cause VWS in these twins are known, the additional mechanism behind their phenotypic risk and variability in expression remains unclear.MethodsWe generated whole genome DNAm data for both twin pairs. Differentially methylated positions (DMPs) were selected based on: (1) a coefficient of variation in DNAm levels in unaffected individuals 5% (Δβ > |0.05|). We then divided the DMPs into two subgroups for each twin pair for further analysis: (1) higher methylation levels in twin A (Twin A > Twin B); and (2) higher methylation levels in twin B (Twin B >Twin A).Results and DiscussionGene ontology analysis revealed a list of enriched genes that showed significant differential DNAm, including clef-associated genes. Among the cleft-associated genes, TP63 was the most significant hit (p = 7.82E-12). Both twin pairs presented differential DNAm levels in CpG sites in/near TP63 (Twin 1A > Twin 1B and Twin 2A < Twin 2B). The genes TP63 and IRF6 function in a biological regulatory loop to coordinate epithelial proliferation and differentiation in a process that is critical for palatal fusion. The effects of the causal mutations in IRF6 can be further impacted by epigenetic dysregulation of IRF6 itself or genes in its pathway. Our data show evidence that changes in DNAm are a plausible mechanism that can lead to markedly distinct phenotypes, even among individuals carrying the same mutation.

Van der Woude syndrome is a rare congenital condition with autosomal dominant traits. This autosomal dominant syndrome had been reported to have a penetrance of 80% with variable expression.[1] This genetic disorder is characterized by the combination of lip pits, cleft lip with or without cleft palate, and cleft palate only. Even within the families, there is a wide variability of affected gene expressions. It is very important to establish the correct diagnosis so that genetic counseling can be recommended in such cases. Here, we report cases of Van der Woude syndrome in the same family having the same genetic inheritance with variable expression.

In Van der Woude syndrome (VWS), a rare congenital disease, lower lip pits (LLPs) can cause an aesthetically significant deformity. Surgical treatment of LLPs is necessary if they cause recurrent inflammation or aesthetic problems. Intraoperatively, surgeons should keep in mind the possibility of deep extension of the sinus tract and the relative deficiency of the midline in VWS, which increases the risk of lip disfigurement. Herein, we emphasize the importance of using a tissue-preserving technique to improve aesthetic results in VWS patients with a sinus tract.

Orofacial clefts are common birth defects and Van der Woude syndrome (VWS) is the most common form of orofacial cleft syndrome, accounting for approximately 2% of patients with a cleft.[1],[2] The cardinal features of VWS are lower lip pits associated with cleft lip and/or palate.[2],[3],[4] Lip pits are reported to occur in over 80% of individuals with VWS.[2] Most reported cases of VWS have been linked to chromosome 1q32-q41.[5],[6],[7] The interferon regulatory factor 6 (IRF6) gene, which is located at 1q32-p41 region, has been implicated in several studies.[2],[8] There are over 300 IRF6 variants that have been identified in patients with VWS, with approximately 50% of these being missense variants.[9] This paper describes a 7.5-year-old male patient that is heterozygous for a missense variant in C.101A >C p.(Lys34Thr) which is likely to be pathogenic.[9] This patient has the cardinal features for VWS but also has duodenal atresia. Neither the truncating variant identified in this patient nor other variants associated with VWS have been previously linked to duodenal atresia.

Background: Congenital maxillomandibular syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology. Case presentation: Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects. Conclusions: Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations. [ABSTRACT FROM AUTHOR]

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. Results: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. Conclusions: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS. [ABSTRACT FROM AUTHOR]

Objective: Van der Woude Syndrome (VWS) presents with combinations of lip pits (LP) and cleft lip and/or cleft palate (CL/P, CPO). VWS phenotypic heterogeneity even amongst relatives, suggests that epigenetic factors may act as modifiers. IRF6, causal for 70% of VWS cases, and TP63 interact in a regulatory loop coordinating epithelial proliferation and differentiation in palatogenesis. We hypothesize that differential DNA methylation within IRF6 and TP63 regulatory regions underlie VWS phenotypic discordance., Methods: DNA methylation of CpG sites in IRF6 and TP63 promoters and in an IRF6 enhancer element was compared amongst blood or saliva DNA samples of 78 unrelated cases. Analyses were done separately for blood and saliva, within each sex and in combination, and to address cleft type (CL/P ± LP vs. CPO ± LP) and phenotypic severity (any cleft + LP vs. any cleft only)., Results: For cleft type, blood samples showed higher IRF6 and TP63 promoter methylation on males with CPO ± LP compared to CL/P ± LP and on individuals with CPO ± LP compared to those with CL/P ± LP, respectively. Saliva samples showed higher IRF6 enhancer methylation on individuals with CPO ± LP compared to CL/P ± LP and contrary to above, lower TP63 promoter methylation on CPO ± LP compared to CL/P ± LP. For phenotypic severity, blood samples showed no differences; however, saliva samples showed higher IRF6 promoter methylation in individuals with any cleft + LP compared to those without lip pits., Conclusion: We observed differential methylation in IRF6 and TP63 regulatory regions associated with cleft type and phenotypic severity, indicating that epigenetic changes in IRF6 and TP63 can contribute to phenotypic heterogeneity in VWS., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity., Methods: The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients., Results: In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome., Conclusions: The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low., (© 2024 Łukasz Wieprzowski et al., published by Sciendo.)

IRF6 is a key genetic determinant of syndromic and non-syndromic cleft lip and palate. The ability to interrogate post-embryonic requirements of Irf6 has been hindered, as global Irf6 ablation in the mouse causes neonatal lethality. Prior work analyzing Irf6 in mouse models defined its role in the embryonic surface epithelium and periderm where it is required to regulate cell proliferation and differentiation. Several reports have also described Irf6 gene expression in other cell types, such as muscle, and neuroectoderm. However, analysis of a functional role in non-epithelial cell lineages has been incomplete due to the severity and lethality of the Irf6 knockout model and the paucity of work with a conditional Irf6 allele. Here we describe the generation and characterization of a new Irf6 floxed mouse model and analysis of Irf6 ablation in periderm and neural crest lineages. This work found that loss of Irf6 in periderm recapitulates a mild Irf6 null phenotype, suggesting that Irf6 -mediated signaling in periderm plays a crucial role in regulating embryonic development. Further, conditional ablation of Irf6 in neural crest cells resulted in an anterior neural tube defect of variable penetrance. The generation of this conditional Irf6 allele allows for new insights into craniofacial development and new exploration into the post-natal role of Irf6 .

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation-c.748C>T:p.R250X-in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6 -p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation's role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFβ2-AS1 expression. The findings highlight the mutation's influence on TGFβ2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS's molecular underpinnings and might inform future therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Cui, Chi, Wan, Ma, Zhang and Cai.)

Background: Van der Woude syndrome (VWS), characterised mainly by lower lip pits and orofacial cleft (OFC), is the most common syndrome associated with an OFC. It is inherited as an autosomal dominant, high penetrance disorder with variable phenotypic expression and caused by the genetic mutation of the interferon regulatory factor 6 gene (IRF6). This study showcases the syndrome's variable phenotypic expressivity in six cases seen at Chu d' Treichvile, Abidjan, and Cote d'Ivoire., Materials and Methods: A review of six cases at the above-named hospital. Data collected include age at presentation, gender, type of cleft, presence or absence of lip pits, and family history of VWS., Results: Six cases of VWS were reviewed with an age range from 2 to 39 years and a male-to-female ratio of 1:2. Three of the patients had a bilateral cleft lip, one case of unilateral cleft lip and palate, another single case of cleft palate only while the sixth patient has no cleft deformity. All the patients have bilateral lower lip pits except one with a single median pit on the lower lip. There is a family history of VWS in three of the patients., Conclusion: Our study demonstrates the variable expressivity of VWS as different forms of lower lip pits and OFC. The presence of lower lip pits should be a signal for examination of family members to identify other cases and those likely to have cleft babies. Genetic mapping to detect mutation of IRF6 genes will be of tremendous aid in the effective diagnosis of VWS., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of West African College of Surgeons.)