|Year : 2022 | Volume
| Issue : 1 | Page : 74-77
Variable expression of Van der Woude syndrome in the same family
Ravi Kumar Mahajan, Sheikh Sarfraz Ali, Sana Jameel, Samik Sharma
Department of Plastic and Reconstructive Surgery, Amandeep Hospital, Amritsar, Punjab, India
|Date of Submission||23-Mar-2021|
|Date of Acceptance||27-Sep-2021|
|Date of Web Publication||01-Jan-2022|
Dr. Sheikh Sarfraz Ali
Department of Plastic and Reconstructive Surgery, Amandeep Hospital, Amritsar, Punjab - 143 001
Source of Support: None, Conflict of Interest: None
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. 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.
Keywords: Cleft lip, cleft palate, lip pit, Van der Woude syndrome
|How to cite this article:|
Mahajan RK, Ali SS, Jameel S, Sharma S. Variable expression of Van der Woude syndrome in the same family. J Cleft Lip Palate Craniofac Anomal 2022;9:74-7
|How to cite this URL:|
Mahajan RK, Ali SS, Jameel S, Sharma S. Variable expression of Van der Woude syndrome in the same family. J Cleft Lip Palate Craniofac Anomal [serial online] 2022 [cited 2022 Jan 25];9:74-7. Available from: https://www.jclpca.org/text.asp?2022/9/1/74/333656
| Introduction|| |
Van der Woude syndrome is a rare congenital condition with autosomal dominant inheritance and a genetic penetrance of 80%–100%. It is the most common syndrome associated with cleft lip or cleft palate. Various manifestations of this syndrome include lower lip pits with or without cleft lip and palate, cleft palate only, and hypodontia. Expression of these traits varies widely among affected individuals. Even the same inherited gene shows variable expression in a mother and child. The most consistent expression found in this syndrome is the presence of pit. It is very important to be aware of this disorder because lower lip pits have also been reported in a variety of other congenital disorders and are associated with other malformations. Cleft lip or cleft palate is associated with 70% of cases of lip pits; this finding suggests that both defects may be part of a syndrome. The incidence of lip pits is estimated to be 1 in 75,000–100,000 individuals. Congenital pits of the lower lip are also characteristically seen in popliteal pterygium syndrome and sometimes also observed in type 1 orofaciodigital syndrome; other additional important associations found are hypodontia, absence of the second premolar, congenital heart disorders, symblepharon, genitourinary anomalies, popliteal pterygium, syndactyly, and disorders of nail growth.
| Case Report|| |
A 5-month-old male baby presented with his parents to our outpatient department for cleft lip and palate defect [Figure 1]. On further examination, there was presence of two symmetrical lower lip pits. There was no history of any discharge from these pits. When family history was traced, the mother was found to have similar lower lip pits along with cleft palate only [Figure 2]. The mother was already operated for cleft palate in childhood. There was no history of any orofacial cleft or lip pits in the father, siblings, and any other family members. There was no history of consanguineous marriage of his parents. According to the mother, the patient was born after a normal, full-term pregnancy with no history of any teratogenic drug intake or exposure to radiation during antenatal period. The child was further examined and investigated, but no other congenital anomaly was found. Surgical interventions were planned in stages for corrections of all deformities. First of all, cheiloplasty was done for cleft lip at the age of 3 months. Palatoplasty was done at the age of 9 months [Figure 3]. Parents did not agree to lip pit surgery at present. Counseling of parents was done for 50% chances of inheriting the gene of Van der Woude syndrome in their next issues.
|Figure 1: Preoperative photo of baby with lower lip pits along with cleft lip and Palate|
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|Figure 3: Post cheiloplasty and palatoplasty photo of baby and mother with lip pits|
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| Discussion|| |
Congenital lower lip pit is one of the most commonly occurring congenital malformations of the lower lip. These pits of the lower lip have a number of peculiar clinical features. These are usually point depressions but sometimes have a slight elevation in the area of the vermilion of the lower lip on both sides of the midline. Lip pits can also be present at various other locations such as at commissure, midline upper lip, and lower lip. Most of the lip pits are asymptomatic, but sometimes, they may drain saliva as sinuses and cause dryness and fissures affecting the mucosal surface of both lips. Histologically, the tract is lined by a stratified, squamous epithelium in continuity with the labial epithelium. The base of the cavity may contain mucosal gland acini with small communicating ductules. The latter can be either open or blind and, in principle, may be presumed to exude the aforementioned mucinous fluid.
Congenital lower lip pit was first reported in the literature by Demarquay in 1845. Gurney in 1940 reported four cases of lip pits in one family; Fogh-Andersen in 1943 reported 11 cases of lip pits in 3 family groups; and Test and Falls in 1947 reported lip pits in five generations of the same family. However, the first comprehensive description was given by Van der Woude in 1954 after carefully studying five pedigrees. He found that the combination of pits of the lower lip with cleft lip and palate is based on a single dominant gene, which he recognized as a syndrome that has since been known as the Van der Woude syndrome. The gene involved in the origin of Van der Woude syndrome is linked to loci on chromosome 1q32-q41. A second chromosomal locus at 1p34 has also been found later. However, recently mutation in the interferon regulatory factor 6 (IRF6) gene has also been identified to be the cause of the Van der Woude syndrome., Seventy-two percent of Van der Woude syndrome is caused by loss-of-function mutations in IRF6 gene. However, dominant-negative variants of Grainyhead-like transcription factor 3 (GRHL3) have been found in 5% of Van der Woude cases without having IRF6 mutation. A rare pathogenic form of missense variant in NME/NM23 nucleoside diphosphate kinase 1 (NME1) has also been recently found in IRF6 and GRHL3 mutation-negative Van der Woude patients.
The cardinal phenotypic expression in various studies of Van der Woude syndrome was reviewed, and it was found that lip pits were associated with other features such as cleft lip, cleft palate, cleft lip and cleft palate, hypodontia, and ankyloglossia. These different phenotypic expressions are observed in different patients with no link to their inheritance and thus variability in their genetic expression can be expected. Here in this study, one generation inheritance of gene that is from the mother to her child showed entirely different phenotypic expressions other than lip pit. Koçer et al. also reported similar findings in mother–child duo. The phenotypic expression in their report suggested one patient with lower lip pits with cleft palate, whereas in the other, there was isolated lower lip pit only. However, the genetic expressions still vary in our cases from Kocer et al. report. The mother in our case report has lip pits along with cleft palate only whereas the baby has lip pits along with cleft of both lip and palates. Even in one case report, the authors had reported four cases with Van der Woude syndrome demonstrating the wide clinical variability. One case, in that report, showed brain abnormalities that might have been a part of the clinical spectrum of Van der Woude syndrome. Jobling et al. presented a case of confirmed monozygotic (MZ) female twins both affected with Van der Woude syndrome due to an IRF6 mutation but with markedly different phenotypes. One baby had bilateral cleft lip and palate whereas the other baby was normal. The twins' father was found to have bilateral paramedian lower lip pits but no orofacial clefting. They generated templates for sequencing of all exons of IRF6 by polymerase chain reaction, and on sequencing, a missense mutation in exon 4 of the IRF6 gene was found in both the twins and their father.
Management of these variable congenital defects is surgical. However, the indications may be functional, curative, or esthetic depending on clinical presentations and demand of patients. Lip pits surgery is usually esthetic, but the rest of other deformity corrections are done for both esthetic and functional indications. At authors' center, cleft lip is corrected first followed by cleft palate. Lip pit correction is usually done at later stage only if patients specially ask for the same. While reviewing the literature, one case report of a carcinoma developing in the area of the lower lip secondary to a chronic inflammatory process has been found. Hence, patients must be aware of this complication, though rare.
| Conclusion|| |
With this case report, our intent is to bring out awareness regarding variable phenotypic expression of the same genotype. The presence of the abovementioned clinical features must be distinguished from other congenital disorders with similar presentation, emphasizing the importance of early recognition of Van der Woude syndrome which may be associated with other malformations. This study also demonstrates the complexity of the expression of the Van der Woude syndrome phenotype and re-emphasizes the need for further studies of modifier genes, epigenetics, and environmental factors. Genetic counseling must be recommended. Need of surgical interventions in various deformities is emphasized.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]