van der Woude Syndrome
- Author: Gregory P Conners, MD, MPH, MBA; Chief Editor: Luis O Rohena, MD more...
van der Woude syndrome is an autosomal dominant syndrome characterized by a cleft lip or cleft palate, distinctive pits of the lower lips, or both. It is the most common syndrome associated with cleft lip or cleft palate. The degree to which individuals who carry the gene are affected widely varies, even within families. These variable manifestations include lower lip pits alone, absent teeth, or isolated cleft lip and cleft palate of varying severity. Hypodontia (absent teeth) has been increasingly recognized as a frequently associated anomaly. Many other associated anomalies have also been described.
The most prominent and consistent features of van der Woude syndrome are orofacial anomalies caused by an abnormal fusion of the palate and lips at 30-50 days postconception. Most cases of van der Woude syndrome have been linked to a deletion in chromosome 1q32-q41; however, a second chromosomal locus at 1p34 has also been identified. The responsible mutation has been identified in the interferon regulatory factor-6 (IRF -6) gene, but the exact mechanism of this mutation on craniofacial development is uncertain.
Demonstrating the presence or absence of an IRF-6 mutation can be helpful when distinguishing between uncomplicated cleft lip and/or cleft palate and van der Woude syndrome. A wide variety of chromosomal mutations that cause van der Woude syndrome and are associated with IRF-6 gene mutations have been described. A potential modifying gene has been identified at 17p11.2-p11.1.
A study by Manjegowda et al found copy number variations affecting IRF6 in members of an Indian family with van der Woude syndrome, suggesting that such variations are involved in the development of the syndrome in the Indian population.
In general, van der Woude syndrome affects about 1 in 100,000-200,000 individuals. About 1-2% of patients with cleft lip or cleft palate have van der Woude syndrome.
The severity of van der Woude syndrome widely varies, even within families. Approximately 25% of individuals with van der Woude syndrome are asymptomatic or have minimal findings, such as absent teeth or trivial indentations in the lower lips. Others have severe clefting in the lip or palate. Lip pits are often associated with accessory salivary glands that empty into the pits, which occasionally leads to embarrassing visible discharge. Hypodontia is present in 10-81% of affected individuals. Most upper and/or lower second premolars are frequently absent.
Differences among races have not been described.
van der Woude syndrome equally affects both sexes. A single, small study has suggested that males with the syndrome may have poorer cognitive function than females.
Manjegowda DS, Prasad M, Veerappa AM, et al. Genome-wide copy number scan identifies IRF6 involvement in Van der Woude syndrome in an Indian family. Genet Res (Camb). 2014 Oct 10. 96:e12. [Medline].
Nopoulos P, Richman L, Andreasen N, Murray JC, Schutte B. Cognitive dysfunction in adults with Van der Woude syndrome. Genet Med. 2007 Apr. 9(4):213-8. [Medline].
Nawa H, Oberoi S, Vargervik K. Taurodontism and Van der Woude syndrome. Is there an association?. Angle Orthod. 2008 Sep. 78(5):832-7. [Medline].
Sarode GS, Desai RS, Sarode SC, Kulkarni MA. Van der Woude syndrome with an unusual intraoral finding. Indian J Dent Res. 2011 Jan-Feb. 22(1):164-5. [Medline].
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. 2009 Nov. 149A(11):2489-92. [Medline].
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. 2009 Oct. 18(4):225-7. [Medline].
Stuppia L, Capogreco M, Marzo G, La Rovere D, Antonucci I, Gatta V, et al. Genetics of syndromic and nonsyndromic cleft lip and palate. J Craniofac Surg. 2011 Sep. 22(5):1722-6. [Medline].
American Academy of Pediatric Dentistry. Clinical guideline on management of persons with special health care needs. Chicago, IL: American Academy of Pediatric Dentistry; 2004.
Bozkurt M, Kulahci Y, Zor F, Kapi E, Yucetas A. Reconstruction of the lower lip in Van der Woude syndrome. Ann Plast Surg. 2009 Apr. 62(4):451-5. [Medline].
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. 2008 Mar. 66(3):589-92. [Medline].
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. 2010 Sep. 21(5):1350-3. [Medline]. [Full Text].
Jobling R, Ferrier RA, McLeod R, Petrin AL, Murray JC, Thomas MA. Monozygotic twins with variable expression of Van der Woude syndrome. Am J Med Genet A. 2011 Aug. 155A(8):2008-10. [Medline].
Silvestre J, Tahiri Y, Paliga JT, et al. Screening for obstructive sleep apnea in children with syndromic cleft lip and/or palate. J Plast Reconstr Aesthet Surg. 2014 Nov. 67(11):1475-80. [Medline].
Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod. 2004 Feb. 26(1):7-16. [Medline].
Du X, Tang W, Tian W, et al. Novel IRF6 mutations in Chinese patients with Van der Woude syndrome. J Dent Res. 2006 Oct. 85(10):937-40. [Medline].
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].
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].
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].
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. 2006 Dec. 85(12):1143-6. [Medline].
Menko FH, Koedijk PH, Baart JA, Kwee ML. Van der Woude syndrome--recognition of lesser expressions: case report. Cleft Palate J. 1988 Jul. 25(3):318-21. [Medline].
Oberoi S, Vargervik K. Hypoplasia and hypodontia in Van der Woude syndrome. Cleft Palate Craniofac J. 2005 Sep. 42(5):459-66. [Medline].
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. 1997 May. 34(3):261-5. [Medline].
Pauli RM, Hall JG. Lip pits, cleft lip and/or palate, and congenital heart disease. Am J Dis Child. 1980 Mar. 134(3):293-5. [Medline].
Puvabanditsin S, Garrow E, Sitburana O, et al. Syngnathia and Van der Woude syndrome: a case report and literature review. Cleft Palate Craniofac J. 2003 Jan. 40(1):104-6. [Medline].
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. 2004 Feb. 26(1):17-24. [Medline].
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. 1999 Aug. 65(2):433-40. [Medline].
Shprintzen RJ, Goldberg RB, Sidoti EJ. The penetrance and variable expression of the Van der Woude syndrome: implications for genetic counseling. Cleft Palate J. 1980 Jan. 17(1):52-7. [Medline].
Tomlinson JK, Liem NT, Savarirayan R, Meara JG. Isolated and syndromic syngnathism: management, implications, and genetics. Ann Plast Surg. 2006 Aug. 57(2):231-5. [Medline].
Van der Woude A. Fistula labii inferioris congenita and its association with cleft lip and palate. Am J Hum Genet. 1954 Jun. 6(2):244-56. [Medline].
Velez A, Alamillos FJ, Dean A, Ruiz-Masera JJ. Congenital lower lip pits (Van der Woude syndrome). J Am Acad Dermatol. 1995 Mar. 32(3):520-1. [Medline].
Vignale R, Araujo J, Pascal G, et al. Van der Woude syndrome. A case report. Pediatr Dermatol. 1998 Nov-Dec. 15(6):459-63. [Medline].