Van der woude syndrome- a case report

Van der Woude syndrome (VWS) is a rare, autosomal dominant disorder, caused by deletions in the chromosome band 1q32-q41, and characterized by cleft lip or cleft palate, distinctive pits of the lower lips, or both. The most prominent and consistent features of Van der Woude syndrome are oro-facial defects. The oro-facial abnormalities include lower lip pits alone, hypodontia, or isolated cleft lip and cleft palate of varying severity. A case of Van der Woude syndrome, with the typical manifestations in a seven year old male patient is being presented, along with its review of literature

van der Woude syndrome- a syndromic form of orofacial clefting

van der Woude Syndrome is the most common form of syndromic orofacial clefting, accounting for 2% of all cases, and has the phenotype that most closely resembles the more common non-syndromic forms. The syndrome has an autosomal dominant hereditary pattern with variable expressivity and a high degree of penetrance with cardinal clinical features of lip pits with a cleft lip, cleft palate, or both. This case report describes van der Woude syndrome in a 19 year old male patient with a specifi c reference to the various aspects of this condition, as clinical appearance, etiological factors (genetic aspects), differential diagnosis, investigative procedures and management

Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation

Congenital lower lip pits : Van der Woude syndrome

The Van der Woude syndrome is a rare autosomal dominant development malformation characterized by a paramedian lip pits and /or sinuses or conical elevation of lower lip associated with cleft lip and or palate. These congenital lip pits usually appear clinically in the vermilion border of lip, with or without secretion. The critical region of VWS has been identified to be at Iq32 to 41 with high, but incomplete penetrance and variable expressivity. Therapeutic intervention is generally required for cosmetic reason or when recurrent inflammation is present. Dental surgeon should be aware of this syndrome, as it is associated with variety of other congenital malformation. van der woude syndrome can be easily missed if it is not in the back of mind and its associated congenital malformation if present. We report a case of lower lip pits with bilateral cleft lip

Van der Woude syndrome and implications in Dental Medicine

There are many types of genetic anomalies that affect the development of orofacial structures. Van der Woude syndrome (VWS), also known as cleft palate, lip pits or lip pit papilla syndrome, is a rare autosomal dominant condition being considered the most common cleft syndrome. It is believed to occur in 1 in 35,000 to 1 in 100,000 individuals, based on data from Europe and Asia. It is characterized by the congenital association of lip sinuses with cleft lip and palate. These are the main traits of VWS and occur in 88% of affected individuals. Another common signal/symptom is hypodontia. Diagnosis of VWS can be done clinically, based on the presence of lip pits and/or other orofacial anomalies that can be present all together or isolated. Most of the development anomalies are congenital so, in most cases, clinical diagnosis can be done immediately after birth. Almost all cases of VWS are linked to a locus in chromosome 1 (q32-q41) also known as VWS locus 1. The IRF6 gene is located at this critical location and encodes the interferon regulatory factor 6. This gene is expressed in the palate, teeth, hair follicles, external genitals and skin. Mutations in this gene are responsible for the development of this pathology. Treatment of patients with this syndrome includes all surgical and multidisciplinary procedures for the correction of the presented anomalies.info:eu-repo/semantics/publishedVersio

Van der Woude syndrome and implications in Dental Medicine

There are many types of genetic anomalies that affect the development of orofacial structures. Van der Woude syndrome (VWS), also known as cleft palate, lip pits or lip pit papilla syndrome, is a rare autosomal dominant condition being considered the most common cleft syndrome. It is believed to occur in 1 in 35,000 to 1 in 100,000 individuals, based on data from Europe and Asia. It is characterized by the congenital association of lip sinuses with cleft lip and palate. These are the main traits of VWS and occur in 88% of affected individuals. Another common signal/symptom is hypodontia. Diagnosis of VWS can be done clinically, based on the presence of lip pits and/or other orofacial anomalies that can be present all together or isolated. Most of the development anomalies are congenital so, in most cases, clinical diagnosis can be done immediately after birth. Almost all cases of VWS are linked to a locus in chromosome 1 (q32-q41) also known as VWS locus 1. The IRF6 gene is located at this critical location and encodes the interferon regulatory factor 6. This gene is expressed in the palate, teeth, hair follicles, external genitals and skin. Mutations in this gene are responsible for the development of this pathology. Treatment of patients with this syndrome includes all surgical and multidisciplinary procedures for the correction of the presented anomalies.info:eu-repo/semantics/publishedVersio

Análise ultra-estrutural das glândulas localizadas na parede da fístula congênita de lábio inferior de pacientes com a síndrome de Van der Woude

The objective of the present study was to evaluate the glands of wall of congenital fistulae of the lower lip with the transmission electron microscope in order to characterize their microstructural pattern. Thin section of Araldite resin embedded congenital fistulae of the lower lip of four patients with Van der Woude syndrome from the Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo, Bauru, SP, were analyzed with a transmission electron microscope. The results showed that the glands were mostly made by typical mucous acini exhibiting, with certain frequency, myoepithelial cells surrounding them. In some of lobules, a few acini smaller than the typical mucous, showed granules of moderate electron density or containing a dense core or exhibiting small dense spherule and predominance granular material. These granules resemble to described recently by others in various human minor salivary glands. We concluded that glands associated with congenital fistula of lower lip of patients with Van der Woude syndrome, in spite of being located in vermilion border of the lip, showed at the transmission electron microscope characteristics of labial minor salivary gland, i.e, are mostly mucous with a few seromucous units, while typical seromucous demilunes are not present.O objetivo do presente estudo foi avaliar a ultraestrutura de glândulas da parede de fístula congênita de lábio inferior ao microscópio eletrônico de transmissão para caracterizar seu padrão microestrutural. Deste modo, as fístulas congênitas de 4 pacientes com a síndrome de Van der Woude do Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de Sâo Paulo, Bauru, SP, foram processadas para inclusão em resina Araldite e os cortes finos foram analisados no microscópio eletrônico de transmissão. Os resultados mostraram que as glândulas estavam constituídas por ácinos mucosos típicos exibindo com certa freqüência células mioepiteliais ao seu redor. Em alguns lóbulos, foram observados em pequeno número, ácinos menores que o mucoso típico, exibindo células com grânulos de moderada eletron-densidade contendo um corpo denso ou uma pequena esférula densa no interior de um material predominante granular. Estes grânulos lembravam os descritos recentemente em glândulas salivares labiais humanas. Em vista dos resultados obtidos concluímos que as glândulas associadas com a fístula congênita de lábio inferior de pacientes com a síndrome de Van der Woude, apesar de estarem localizadas no vermelhão do lábio, mostraram ao microscópio eletrônico de transmissão características de glândula salivar labial, i.e., são predominantemente mucosos com poucas unidades seromucosas, mas semiluas seromucosas típicas não estão presentes

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

Síndromes muy poco frecuentes.

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCAs in previous years, six new syndromes have been selected to be included in this section, aimed to make easier the recognition of syndromes with low-frequency by paediatricians and first health care physicians, particularly those of rural areas. In this Boletín, the following syndromes are included: Megalencephaly-Cutis Marmorata Telangiectatica Congenita syndrome, Van der Woude syndrome, Hay Wells syndrome, Zellweger syndrome, Jeune syndrome and Laurin-Sandrow syndrome. For each syndrome, the most important clinical characteristics, and the present knowledge on their causal factors and mechanisms involved are sumarized.N

Bilateral microform cleft lip

Microform cleft lip (MCL), also called congenital healed cleft lip or cleft lip "frustré", is a rare congenital anomaly. MCL has been described as having the characteristic appearance of a typical cleft lip which has been corrected in utero. We present a girl with bilateral microform cleft lip associated with a preauricular sinus and bilateral camptodactyly.peer-reviewe