van der Woude Syndrome Clinical Presentation

Updated: Apr 13, 2015
  • Author: Gregory P Conners, MD, MPH, MBA; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Presentation

History

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  • Because of its variability, obtaining a detailed family history is important in diagnosing van der Woude syndrome. However, approximately 30-50% of all cases of van der Woude syndrome arise as a de novo mutation.
  • The pedigree should suggest an autosomal dominant inheritance pattern, unless the phenotype is the result of a de novo mutation in the affected individual. Expressivity also widely varies, and careful clinical examination of parents and relatives may be necessary.
  • Physical examination of relatives, close examination of family photos, or interviews of older relatives may be necessary to identify minimally affected family members.
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Physical

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  • Orofacial manifestations
    • van der Woude syndrome is characterized by cleft lip and/or cleft palate and distinctive lower lip pits. This combination is present in approximately 70% of overtly affected individuals but is present in less than one half of those who carry the gene.
    • Severity may widely vary, even in members of the same family.
  • Cleft lip and cleft palate
    • The cleft lip and cleft palate may be isolated.
    • The severity of these anomalies widely varies and may be unilateral or bilateral.
    • Submucous cleft palate is common and may be easily missed during physical examination.
    • Hypernasal voice and cleft or bifid uvula may be present. A bifid uvula is also a possible isolated finding in certain individuals with van der Woude syndrome.
  • Lip pits
    • Lower lip pits are fairly distinctive. The pits are usually medial, often (but not always) on the vermilion portion of the lower lip. They tend to be centered on small elevations in infancy but become simple depressions by adulthood; however, the presentation varies. They are usually bilateral but are occasionally median or paramedian or unilateral and are most often found on the left side.
    • Visible or expressible saliva may be present in the lip pits because of an association with the accessory salivary glands. Pits may lead to tracts that are surprisingly long, making surgical removal challenging.
    • Lip pits may be the only abnormality.
  • Teeth: Hypodontia may be observed and most commonly presents as missing maxillary or mandibular second premolars or maxillary lateral incisors. This may be the only symptom. An association of van der Woude syndrome and taurodontism (teeth with greatly enlarged pulp chambers) has been reported. [3] Dental fusion has also been reported. [4]
  • Other oral manifestations: Although infrequently reported, other symptoms include syngnathia (congenital adhesion of the jaws); narrow, high, arched palate; and ankyloglossia (short glossal frenulum or tongue-tie). A patient without lip pits, oral clefts, or hypodontia but with a heart-shaped mass of the lower lip has been described. [5]
  • Extraoral manifestations
    • Extraoral manifestations are rare but include limb anomalies, popliteal webs, and brain abnormalities.
    • Accessory nipples, congenital heart defects, and Hirschsprung disease have been reported.
    • Extraoral manifestations may be unassociated additional anomalies or infrequently expressed aspects of van der Woude syndrome.
    • Signs of van der Woude syndrome have been seen in individuals with popliteal pterygium syndrome, which has also been linked to mutations in the same gene. These 2 entities are believed to be allelic variants of the same condition; some have described these entities as being part of a van der Woude syndrome–popliteal pterygium syndrome (VWS–PPS) spectrum. [6]
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Causes

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  • van der Woude syndrome is transmitted in autosomal dominant fashion.
  • Penetrance has been reported to be 75% but is likely closer to 100% if appropriate family members are closely examined for minor expressions of the syndrome.
  • The gene for van der Woude syndrome has been localized to chromosome 1q32-q41. Intriguing linkage studies have suggested that a second modifying gene mapped to chromosome 17p11.2-p11.1 may influence the degree of phenotypic expression of a gene defect at this locus. A second chromosome locus for van der Woude syndrome has been mapped to 1p34.
  • The interferon regulatory factor-6 ( IRF-6) gene has been identified as the specific gene usually responsible for van der Woude syndrome [7] ; this gene has been shown to regulate fetal craniofacial development in mice.
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