Van der Woude syndrome is a genetically determined complex of orofacial defects, the most specific of which are facial clefts, hypodontia, paramedian sinuses of the lower lip. There are also other dysplastic stigmas: short lingual frenulum, arched palatine vault, rarely – CHD, abnormalities of limb development. The examination includes genodiagnostics, Rg/CT of the facial skull, ultrasound of internal organs, assessment of neurological status. The treatment of defects is surgical (cheylorinoplasty, uranoplasty). Children with this disease need the help of a speech pathologist.
Q38.0 Congenital anomalies of the lips, not classified elsewhere
Van der Woude syndrome (SVV) is a rare congenital pathology characterized by a triad of maxillofacial anomalies: dimples in the lower lip (80%), cleft lip or cleft palate (21%) and the absence of some teeth (10-81%). SVV was described as an independent disease in 1954. The frequency in the European and Asian populations is 1:80,000‒100,000, regardless of the sex of newborns. Van der Woude syndrome is the most common genetic cause of maxillofacial cleft.
Van der Woude syndrome is an autosomal dominant malformation with incomplete penetrance (80%) and variable expressiveness. More than 68% of cases of pathology are caused by a mutation of the IRF6 gene, which is located in the 1q32-q41 region on the long arm of the 1st chromosome.
The IRF6 gene encodes a special protein ‒ interferon-regulating transcription factor 6, whose function is to regulate the differentiation of epithelial tissue, including that lining the oral cavity and palate. IRF6 mutations are associated with Van der Woude syndrome and phenotypically similar popliteal pterygium syndrome.
A smaller proportion of cases of Van der Woude syndrome (approximately 5%) is associated with genetic damage to another activator of epidermal differentiation ‒ the GRHL3 gene. The involvement of other candidate genes in the development of the syndrome, in particular, located in the 17p11.2-p11 region, is also considered.1.
The inheritance of the defective gene comes from one of the parents, but about 30-50% of cases are caused by de novo mutations. The most typical anomalies of the lips and palate for the syndrome are formed with between 30 and 50 days of intrauterine development.
Normally, on the 32nd day of embryogenesis, there are 4 centers of development of the lower lip, separated by one median and two lateral furrows. By day 38, the rudiments merge with the disappearance of the grooves. However, with a violation of the development of the mandibular process, the lateral furrows remain, and on the 36th day of embryonic development, paramedian sinuses (dimples) of the lower lip are formed from them.
The formation of cleft lips (cheiloschisis) occurs as a result of incomplete fusion of the nasolabial tubercle and the maxillary process. Cleavage of the hard palate occurs due to non-fusion of the palatine protrusions of the maxillary processes.
The manifestations of Van der Woude syndrome are variable even within the same family. The main orofacial anomalies characterizing hereditary pathology ‒ dimples on the lip, facial cleft and hypodontia ‒ can occur in various variations. 44% of patients have dimples without cleavage of the lip and palate, 26% ‒ dimples with cleft, 10% ‒ cleft without dimples and 20% ‒ other dental anomalies, more often hypodontia.
Maxillofacial clefts in SVV vary from submucous defects and unilateral cleft lip to complete bilateral cleavage of the palate and lip. The presence of these defects in children is associated with a whole range of problems: feeding difficulties, frequent infections, open rhinolalia.
The labial pits, or paramedian sinuses, represent small depressions on the lower lip. Usually they are paired, their bottom is lined with a mucous membrane, and saliva forms inside the sinuses, which flows out through the excretory ducts that open on the red border. In some cases of Van der Woude syndrome, there are fistulas or cysts of the lower lip. All children with similar defects have a visually noticeable deformation of the lip.
Carriers of the syndrome often lack some teeth in both dental arches (incisors, canines, premolars). Often there is a Gothic vault of the palate, a shortened sublingual ligament, leading to a bifurcation of the tip of the tongue.
Concomitant skeletal abnormalities may include syndactyly of the hands, hypoplasia of the thumb, clubfoot. Other associated defects are represented by additional nipples (epithelium), heart murmurs, congenital cardiac defects. Intellectual and physical development in Van der Woude syndrome does not suffer.
The presence of a number of orofacial defects leaves an imprint on the functioning of the dental, respiratory, and speech systems. Patients with palatine clefts are prone to recurrent ENT infections: sinusitis, otitis media, laryngotracheitis. Abnormal development of teeth leads to the formation of a defective bite, chewing disorders, early and multiple caries.
The constant release of saliva from the labial pits causes chronic cheilitis, the formation of mucocele and even squamous cell lip cancer is possible. In the speech status of children, rhinolalia is detected, less often – mechanical dyslalia, the consequence of which is FFN or ONR.
The diagnosis is based on the identification of typical clinical signs confirmed by molecular genetic research. Family members should be consulted by a medical geneticist, the child additionally by a maxillofacial surgeon, dentist, speech therapist.
- General inspection. It is necessary for the correct assessment of the phenotype. For Van der Woude syndrome, the presence of pits of the lower lip in combination with a palatine or labial cleft, hypodontia is pathognomonic. The assessment of physical development (anthropometry), the study of neurological status is carried out.
- Genetic diagnostics. A geneticist collects a family history, reveals the peculiarities of the course of pregnancy in the mother of a sick child. The direct sequencing method searches for mutations in the IRF6 gene and, if necessary, in the GRHL3 gene, and searches for identified mutations in relatives.
- Examination of the maxillofacial system. It is required in the preoperative period to clarify the nature of CHLO defects. Radiography and CT of the facial skeleton and jaws have a sufficient degree of informativeness.
- Examination of other organs and systems. In order to exclude concomitant pathologies, ultrasound of the heart and internal organs, ECG is performed. In the presence of skeletal pathology, radiography of the hands and foot bones is prescribed. If sensorineural hearing loss is suspected, an audiometric hearing assessment is performed.
- Consultation of a speech therapist. It is indicated for children who have speech problems associated with ankyloglossia or facial cleft. As part of speech therapy diagnostics, the sound side of speech, phonemic hearing, vocabulary, grammar, etc. are examined. The structure of the speech defect is determined, a logotherapy plan is built.
Prenatal diagnosis of Van der Woude syndrome is indicated if it is known that there is a carrier of the pathogenic gene in the family. Cleft CHLO in the fetus can be detected during ultrasound screening. Van der Woude syndrome is differentiated with nonsyndromic maxillofacial clefts, popliteal fold syndrome, Kabuki syndrome.
Correction of anomalies of the maxillofacial region is performed surgically. The timing and methods depend on the nature of the defects, their impact on the patient’s vital activity. Primary rhinocheiloplasty is performed in the first months of a child’s life, velopharyngoplasty – in 6-8 months, uranoplasty – in 10-14 months. Also at an early age, excision of paramedian sinuses, congenital fistulas, cysts of the lower lip is shown.
In the future, additional reconstructive operations are carried out (bone grafting of the alveolar process, aesthetic cheiloplasty, etc.). According to the indications, the issue of surgical correction of syndactyly, CHD, removal of additional mammary glands is being resolved.
Other treatment and rehabilitation
Classes with a speech therapist are conducted both before and after surgical treatment. The obligatory components of speech rehabilitation are speech therapy massage, breathing and articulation gymnastics. Work is underway on the formation of a full-fledged palatopharyngeal closure, correct sound pronunciation, phonemic hearing, coherent speech, voice modulations.
Carious foci are subject to rehabilitation, malocclusion requires correction with the help of braces. The child and parents are taught the rules of oral hygiene.
Prognosis and prevention
The quality of life of patients with Van der Woude syndrome depends on the number and combination of developmental abnormalities, the possibility and timing of their correction. Isolated clefts are subject to surgical treatment in early childhood. In the future, children can lead a full-fledged lifestyle on a par with their peers. The presence of defects of vital organs makes the prognosis heavier.
Preventive work is being carried out in the direction of medical and genetic counseling, forecasting the likelihood of Van der Woude syndrome in subsequent generations. When fetal malformations are detected as part of prenatal ultrasound screening, pregnant parents are informed about possible risks and treatment tactics.