Prenatal diagnosis and management of Van der Woude syndrome

Introduction

Van der Woude syndrome (VWS) is a rare congenital defect with an incidence of one out of 35,000–100,000 newborns and consists of the existence of lip and/or palate cleft associated with pits in the inferior lip, and other malformations such as heart, musculoskeletal, and genitourinary diseases [1].

We report a case of VWS after ultrasound prenatal diagnosis of right cleft lip and palate in a 21 weeks’ foetus. We describe postnatal anatomical findings and the management reported in the literature on this syndrome.

Presentation of the case

A 22-year-old primigravida presented to our Foetal Medicine Unit at 21 weeks. The first trimester chromosomal screening was normal. On the ultrasound scan we detected a fusion defect at the right maxillary edentulous arch and at the hard ipsilateral palate, corresponding with right complete cleft lip and palate (CLP) (Figure 1A and B). Detailed anatomical ultrasound did not show other malformations and foetal growth was in accordance with gestational age. After normal echocardiography study and multidisciplinary counselling, including with the paediatric plastic surgery department, the parents declined to perform any invasive tests such as amniocentesis.

Figure 1:

Echographic fetal axial cut. (A) This figure shows the level of the dental arch of the upper palate. (B) In a slightly smaller level, the figure shows the defect both at the palate level (cleft palate) and the cleft lip in the right side.

Consecutive foetal ultrasound and maternal control were normal and our patient delivered vaginally, at term, a 3700 g female with a normal perinatal outcome.

Postnatal anatomical findings confirmed right complete CLP and two little dimples were detected at each side of the middle line of the lower lip (Figure 2). We conducted an exhaustive familiar anamnesis and the parents referred a cousin who presented with congenital and isolated lip pits.

Figure 2:

Picture taken after birth. The defect in the right side of the upper lip is shown in the inset. While examining, we confirmed a wide complete right cleft lip and palate.

Plastic surgery was performed during the first month of life to improve breast feeding and for the weight gain of the newborn. The postoperative course was successful and the patient was discharged a week later with an uneventful evolution.

At the present time, the girl is 6 months old and maintains an appropriate weight gain (Figure 3). Palate repair along with the likely removal of lip pits is expected, according to protocol, at 9 months of age, followed by alveolar bone graft at age 11.

Figure 3:

Image 1 month after the intervention (cheiloplasty) where we observed more clearly the existence of two pits at each side of the middle line of the lower lip.

Discussion

We report a case of VWS after prenatal diagnosis of cleft lip and palate and postnatal anatomical findings of lip pits without other malformations, and its intra/post surgical normal evolution.

Orofacial clefting represents the most common congenital facial malformation [2] and VWS is the first syndrome associated with facial defects. Pits or lip dimples, which are present in 90% of the cases, constitute the cardinal sign of this syndrome [3]. Lip pits are mucous cavities that pass through the face’s orbicularis muscle. They are generally asymptomatic, but they can also drain continuous or intermittent salivary secretion, which could imply risk of infection [4]. This syndrome presents a dominant hereditary pattern with high penetrance and highly variable expression. This is why, if there is a case in a certain family, we must take it into consideration. Likewise, this high variability in expressivity must be taken into account in the prenatal diagnosis and genetic counselling. If there is a family history of lip pits, we must always look for possible clefts in the offspring, apart from carrying out an exhaustive morphological study. In general, 80% of people affected by this syndrome have lip dimples or pits, 30% have cleft lip with or without cleft palate, and 15% have isolated cleft palate [5].

The latest ultrasound advances, including 3D or 4D ultrasound, have enabled to detect facial defects during the prenatal period and molecular genetics improvements allow us to identify inheritable defects such as VWS. Therefore, after the ultrasound prenatal diagnosis or family history of facial defects, a detailed ultrasound should be performed and familiar anamnesis is recommended to rule out VWS.

The above-mentioned variability of VWS is due to several associated mutations that have been described and that involve the existence of different variants: the classic form or type 1 VWS, linked to chromosome 1(1q32) (OMIM#119300), affects the already mentioned FRI6 gene [6], and the classic type 2 form, also linked to chromosome 1(1q34) (OMIM#606713) affects the WDR65 gene. The type 2 form, present in Finish families, works in a very similar way to non-syndrome phenotypes, where several environmental factors are also involved in the malformation [7]. The modified form of type 1 VWS that adds the mutation of the chromosome 1, and also chromosome 17(17p11.2-11.2), have been described, and it has been demonstrated that the degree of expression of VWS may depend on the existence of other genetic alterations.

Besides genetic causes, other environmental factors have been related to facial clefts and could increase the prevalence of cases in an affected family. These are, among others: tobacco, antiepileptic drugs and, more controversial, folic acid deficiency.

Due to high penetrance and variable expression, parents at risk should be counselled and consecutive ultrasound and echocardiography scan should be performed even in case of a mild familiar defect [8].

After demonstrating the hereditary pattern and the genetic alterations of this syndrome, it is mandatory to suggest genetic counselling to those people with family or personal history of lip dimples with or without cleft lip and palate.

It is necessary to inform parents from the beginning and furnish them with clear information about these defects, this may help its acceptance. In many cases, it consists of a isolated correctable malformation with excellent post surgical aesthetic outcome.