van der Woude Syndrome Clinical Presentation

  • Author: Gregory P Conners, MD, MPH; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Sep 13, 2011
 

History

  • 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

  • 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 symptoms 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 symptom.
  • 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.[2]
  • 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.[3]
  • 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.[4]
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Causes

  • van der Woude syndrome is transmitted in autosomal dominant fashion.
  • Penetrance has been reported to be 75% but is likely closer to 100% if supposedly unaffected carriers 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 tentatively identified as the specific gene responsible for van der Woude syndrome; this gene has been shown to regulate fetal craniofacial development in mice.
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Contributor Information and Disclosures
Author

Gregory P Conners, MD, MPH  Chief, Division of Emergency Medical Services, Children's Mercy Hospital; Vice Chair of Pediatrics for Emergency and Urgent Care; Professor of Pediatrics and Emergency Medicine, University of Missouri-Kansas City School of Medicine

Gregory P Conners, MD, MPH is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American College of Emergency Physicians, American Pediatric Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Ian Krantz, MD  Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia

Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina School of Medicine; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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  2. Nawa H, Oberoi S, Vargervik K. Taurodontism and Van der Woude syndrome. Is there an association?. Angle Orthod. Sep 2008;78(5):832-7. [Medline].

  3. Yeetong P, Mahatumarat C, Siriwan P, Rojvachiranonda N, Suphapeetiporn K, Shotelersuk V. Three novel mutations of the IRF6 gene with one associated with an unusual feature in Van der Woude syndrome. Am J Med Genet A. Nov 2009;149A(11):2489-92. [Medline].

  4. Houweling AC, Gille JJ, Baart JA, van Hagen JM, Lachmeijer AM. Variable phenotypic manifestation of IRF6 mutations in the Van der Woude syndrome and popliteal pterygium syndrome: implications for genetic counseling. Clin Dysmorphol. Oct 2009;18(4):225-7. [Medline].

  5. American Academy of Pediatric Dentistry. Clinical guideline on management of persons with special health care needs. Chicago, IL: American Academy of Pediatric Dentistry; 2004.

  6. Bozkurt M, Kulahci Y, Zor F, Kapi E, Yucetas A. Reconstruction of the lower lip in Van der Woude syndrome. Ann Plast Surg. Apr 2009;62(4):451-5. [Medline].

  7. Krauel L, Parri FJ, Munoz E, Sancho AM, Gean E, Morales L. Van der Woude Syndrome and lower lip pits treatment. J Oral Maxillofac Surg. Mar 2008;66(3):589-92. [Medline].

  8. Jones JL, Canady JW, Brookes JT, Wehby GL, L'Heureux J, Schutte BC, et al. Wound complications after cleft repair in children with Van der Woude syndrome. J Craniofac Surg. Sep 2010;21(5):1350-3. [Medline]. [Full Text].

  9. Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod. Feb 2004;26(1):7-16. [Medline].

  10. Du X, Tang W, Tian W, et al. Novel IRF6 mutations in Chinese patients with Van der Woude syndrome. J Dent Res. Oct 2006;85(10):937-40. [Medline].

  11. Ghassibe M, Bayet B, Revencu N, et al. Orofacial clefting: update on the role of genetics. B-ENT. 2006;2 Suppl 4:20-4. [Medline].

  12. Janku P, Robinow M, Kelly T, et al. The van der Woude syndrome in a large kindred: variability, penetrance, genetic risks. Am J Med Genet. 1980;5(2):117-23. [Medline].

  13. Lacombe D, Pedespan JM, Fontan D, Chateil JF, Verloes A. Phenotypic variability in van der Woude syndrome. Genet Couns. 1995;6(3):221-6. [Medline].

  14. Matsuzawa N, Shimozato K, Natsume N, Niikawa N, Yoshiura K. A novel missense mutation in Van der Woude syndrome: usefulness of fingernail DNA for genetic analysis. J Dent Res. Dec 2006;85(12):1143-6. [Medline].

  15. Menko FH, Koedijk PH, Baart JA, Kwee ML. Van der Woude syndrome--recognition of lesser expressions: case report. Cleft Palate J. Jul 1988;25(3):318-21. [Medline].

  16. Oberoi S, Vargervik K. Hypoplasia and hypodontia in Van der Woude syndrome. Cleft Palate Craniofac J. Sep 2005;42(5):459-66. [Medline].

  17. Onofre MA, Brosco HB, Taga R. Relationship between lower-lip fistulae and cleft lip and/or palate in Von der Woude syndrome. Cleft Palate Craniofac J. May 1997;34(3):261-5. [Medline].

  18. Pauli RM, Hall JG. Lip pits, cleft lip and/or palate, and congenital heart disease. Am J Dis Child. Mar 1980;134(3):293-5. [Medline].

  19. Puvabanditsin S, Garrow E, Sitburana O, et al. Syngnathia and Van der Woude syndrome: a case report and literature review. Cleft Palate Craniofac J. Jan 2003;40(1):104-6. [Medline].

  20. Rizos M, Spyropoulos MN. Van der Woude syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling and treatment. Eur J Orthod. Feb 2004;26(1):17-24. [Medline].

  21. Sertie AL, Sousa AV, Steman S, et al. Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11.2-11.1. Am J Hum Genet. Aug 1999;65(2):433-40. [Medline].

  22. Shprintzen RJ, Goldberg RB, Sidoti EJ. The penetrance and variable expression of the Van der Woude syndrome: implications for genetic counseling. Cleft Palate J. Jan 1980;17(1):52-7. [Medline].

  23. Tomlinson JK, Liem NT, Savarirayan R, Meara JG. Isolated and syndromic syngnathism: management, implications, and genetics. Ann Plast Surg. Aug 2006;57(2):231-5. [Medline].

  24. Van der Woude A. Fistula labii inferioris congenita and its association with cleft lip and palate. Am J Hum Genet. Jun 1954;6(2):244-56. [Medline].

  25. Velez A, Alamillos FJ, Dean A, Ruiz-Masera JJ. Congenital lower lip pits (Van der Woude syndrome). J Am Acad Dermatol. Mar 1995;32(3):520-1. [Medline].

  26. Vignale R, Araujo J, Pascal G, et al. Van der Woude syndrome. A case report. Pediatr Dermatol. Nov-Dec 1998;15(6):459-63. [Medline].

 
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Cleft lip and cleft palate in an infant with van der Woude syndrome. (Photo courtesy of Mary J. Hauk, DDS.)
Closer view of cleft lip and cleft palate in an infant with van der Woude syndrome, showing raised pits of lower lip. (Photo courtesy of Mary J. Hauk, DDS.)
Intraoral view of cleft lip and cleft palate in an infant with van der Woude syndrome. (Photo courtesy of Mary J. Hauk, DDS.)
 
 
 
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