“VAN DER WOUDE SYNDROME: REPORT OF TWO CASES”

Van Der Woude syndrome is a rare autosomal dominant condition which is associated with developmental malformations involving lips, palate. This syndrome can be a genetic origin due to Microdeletion of chromosome bands 1q32-q41 and also mutation of Interferon regulatory factor 6 (IRF-6) can be a pathogenic cause. We report two interesting cases of Van Der Woude syndrome with lip pits and orofacial features.

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Mutations in P63 and IRF-6 Present with Overlapping Craniofacial Defects: A study from Lebanon

10.31487/j.ord.2019.01.04 ◽

2019 ◽

pp. 1-3

Author(s):

Mazen Kurban ◽

Edgar Jabbour ◽

Lamiaa Hamie ◽

Mazen Kurban ◽

Pamela Kassabian

Keyword(s):

Transcription Factors ◽

Cleft Lip ◽

Interferon Regulatory Factor ◽

Craniofacial Development ◽

Regulatory Factor ◽

Van Der Woude Syndrome ◽

Interferon Regulatory Factor 6 ◽

Cleft Lip Palate ◽

Exon 9 ◽

Craniofacial Defects

Interferon Regulatory Factor 6 (IRF-6) and p63 are two vital transcription factors implicated in normal craniofacial development. In this report, we present a family with Van Der Woude Syndrome (VWS) with a mutation in exon 9 of IRF-6 gene and a phenotypically overlapping case of Rapp-Hodgkin Syndrome (RHS) resulting from a mutation in the p63 gene. Members from both families presented with congenital lip pits and cleft lip/palate. The RHS case had additional ectodermal features that underscore the upstream nature of p63 in the complex p63-IRF-6 interactive pathway.

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A Novel Interferon Regulatory Factor 6 Mutation in an Asian Family with Van der Woude Syndrome

The Cleft Palate-Craniofacial Journal ◽

10.1597/15-327 ◽

2017 ◽

Vol 54 (4) ◽

pp. 442-445 ◽

Cited By ~ 1

Author(s):

Ene-Choo Tan ◽

Hwee-Woon Lim ◽

Eileen C.P. Lim ◽

Seng-Teik Lee

Keyword(s):

Direct Sequencing ◽

Phenotypic Variability ◽

Genetic Disorder ◽

Female Gender ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Van Der Woude Syndrome ◽

Orofacial Clefting ◽

Interferon Regulatory Factor 6 ◽

Transition Mutation

Van der Woude syndrome (VWS) is a rare autosomal dominant genetic disorder characterized by orofacial clefting and lip pits. Mutations in the transcription factor interferon regulatory factor 6 gene ( IRF6) have been identified in individuals with VWS. We performed direct sequencing of the gene for molecular investigation of a proband with Bangladeshi-Malay ancestry. A novel transition mutation (c.113T>C), which resulted in an amino acid substitution (p.Ile38Thr) in the deoxyribonucleic acid-binding domain was detected. Testing of family members showed that the mutation segregated with the VWS phenotype for members of her immediate family. Although there is some phenotypic variability, all of the affected members are of the female gender.

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Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

Genetics in Medicine ◽

10.1097/gim.0b013e318197a49a ◽

2009 ◽

Vol 11 (4) ◽

pp. 241-247 ◽

Cited By ~ 77

Author(s):

Renata L L Ferreira de Lima ◽

Sarah A Hoper ◽

Michella Ghassibe ◽

Margaret E Cooper ◽

Nicholas K Rorick ◽

...

Keyword(s):

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Van Der Woude Syndrome ◽

Interferon Regulatory Factor 6 ◽

Nonrandom Distribution ◽

Popliteal Pterygium Syndrome ◽

Popliteal Pterygium

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Novel IRF6 Mutations in Chinese Patients with Van der Woude Syndrome

Journal of Dental Research ◽

10.1177/154405910608501013 ◽

2006 ◽

Vol 85 (10) ◽

pp. 937-940 ◽

Cited By ~ 11

Author(s):

X. Du ◽

W. Tang ◽

W. Tian ◽

S. Li ◽

X. Li ◽

...

Keyword(s):

Cleft Palate ◽

Cleft Lip ◽

Interferon Regulatory Factor ◽

Binding Domain ◽

Chinese Patients ◽

Regulatory Factor ◽

Van Der Woude Syndrome ◽

Lower Lip ◽

Chinese Families ◽

Interferon Regulatory Factor 6

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. Abbreviations: VWS, Van der Woude syndrome; IRF6, interferon regulatory factor 6; CL/P, cleft lip and/or cleft palate; DBD, DNA-binding domain; SMIR, Smad-interferon regulatory factor-binding domain; Kb, kilobase; PCR, polymerase chain-reaction.

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Interferon Regulatory Factor 6 Controls Proliferation of Keratinocytes from Children with Van der Woude Syndrome

The Cleft Palate-Craniofacial Journal ◽

10.1597/15-275 ◽

2017 ◽

Vol 54 (3) ◽

pp. 281-286 ◽

Cited By ~ 4

Author(s):

Katherine Hixon ◽

Lindsey Rhea ◽

Jennifer Standley ◽

Frank J. Canady ◽

John W. Canady ◽

...

Keyword(s):

Proliferating Cell Nuclear Antigen ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Interferon Regulatory Factor ◽

Nuclear Antigen ◽

Regulatory Factor ◽

Van Der Woude Syndrome ◽

Increased Risk ◽

Interferon Regulatory Factor 6 ◽

Proliferating Cell

Objective Interferon Regulatory Factor 6 (IRF6) is critical for craniofacial development, epidermal differentiation, and tissue repair. IRF6 mutations cause Van der Woude Syndrome (VWS) and Popliteal Pterygium Syndrome. Individuals with VWS exhibit craniofacial anomalies, including cleft lip and palate and lip pits. Furthermore, they have an increased risk for wound-healing complications following surgical repair when compared with patients with nonsyndromic cleft lip and palate (NSCLP). However, nothing is known about the skin of these patients. The objective was to characterize the skin of patients with VWS. We hypothesize that IRF6 is required for proper skin homeostasis in humans. Design Discarded tissue from a hip was collected during surgical alveolar bone graft. Samples from children with VWS harboring IRF6 mutations ( n = 2) were compared with samples from children with NSCLP ( n = 7). Histology was assessed following hematoxylin and eosin staining. The expressions of Proliferating Cell Nuclear Antigen, IRF6, P63, and Keratin 10 were determined by immunofluorescence. Keratinocytes were isolated and their proliferation potential was assessed by colony-forming efficiency assay. Results Hip skin from children with VWS showed a thicker epidermis when compared with that from children with NSCLP. Proliferating Cell Nuclear Antigen staining revealed an increase in proliferation in syndromic tissues when compared with controls. However, P63 and Keratin 10 expression were similar between groups. Finally, keratinocytes from VWS showed increased long-term proliferation when compared with NSCLP. Conclusions These results support, in vivo and in vitro, a previously described role for IRF6 in epidermal proliferation in humans. They further demonstrate a critical function for IRF6 in cutaneous homeostasis.

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