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Oral-facial-digital syndrome

Reviewed February 2010

What is oral-facial-digital syndrome?

Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).

Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.

The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.

Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.

Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).

Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome.

Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.

How common is oral-facial-digital syndrome?

Oral-facial-digital syndrome has an estimated incidence of 1 in 50,000 to 250,000 newborns. Type I accounts for the majority of cases of this disorder. The other forms of oral-facial-digital syndrome are very rare; most have been identified in only one or a few families.

What genes are related to oral-facial-digital syndrome?

Only one gene, OFD1, has been associated with oral-facial-digital syndrome. Mutations in this gene cause oral-facial-digital syndrome type I. OFD1 gene mutations were also found in an affected family whose disorder was classified as type VII; however, researchers now believe that type VII is the same as type I.

The OFD1 gene provides instructions for making a protein whose function is not fully understood. It appears to play an important role in the early development of many parts of the body, including the brain, face, limbs, and kidneys. Mutations in the OFD1 gene prevent cells from making enough functional OFD1 protein, which disrupts the normal development of these structures. It is unclear how a shortage of this protein causes the specific features of oral-facial-digital syndrome type I.

Researchers are actively searching for the genetic changes responsible for the other forms of oral-facial-digital syndrome.

Related Gene(s)

Changes in this gene are associated with oral-facial-digital syndrome.

  • OFD1

How do people inherit oral-facial-digital syndrome?

Oral-facial-digital syndrome type I is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of OFD1 protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of oral-facial-digital syndrome type I.

In males (who have only one X chromosome), mutations result in a total loss of the OFD1 protein. A lack of this protein is usually lethal very early in development, so very few males are born with oral-facial-digital syndrome type I. Affected males usually die before birth, although a few have lived into early infancy.

Most of the other forms of oral-facial-digital syndrome are inherited in an autosomal recessive pattern, which suggests that both copies of a causative gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of oral-facial-digital syndrome?

These resources address the diagnosis or management of oral-facial-digital syndrome and may include treatment providers.

  • Gene Review: Oral-Facial-Digital Syndrome Type I (http://www.ncbi.nlm.nih.gov/books/NBK1188)
  • Genetic Testing Registry: Mohr syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0026363)
  • Genetic Testing Registry: Oral-facial-digital syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1510460)
  • Genetic Testing Registry: Orofacial-digital syndrome III (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0406726)
  • Genetic Testing Registry: Orofacial-digital syndrome IV (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0406727)
  • Genetic Testing Registry: Orofaciodigital syndrome 10 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1833796)
  • Genetic Testing Registry: Orofaciodigital syndrome 11 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2752048)
  • Genetic Testing Registry: Orofaciodigital syndrome 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868118)
  • Genetic Testing Registry: Orofaciodigital syndrome 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2745997)
  • Genetic Testing Registry: Orofaciodigital syndrome 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796100)
  • Genetic Testing Registry: Orofaciodigital syndrome 8 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796101)
  • Genetic Testing Registry: Orofaciodigital syndrome 9 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796102)
  • Genetic Testing Registry: Orofaciodigital syndromes (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0029294)
  • MedlinePlus Encyclopedia: Cleft Lip and Palate (http://www.nlm.nih.gov/medlineplus/ency/article/001051.htm)
  • MedlinePlus Encyclopedia: Polycystic Kidney Disease (http://www.nlm.nih.gov/medlineplus/ency/article/000502.htm)
  • MedlinePlus Encyclopedia: Polydactyly (http://www.nlm.nih.gov/medlineplus/ency/article/003176.htm)

You might also find information on the diagnosis or management of oral-facial-digital syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/oral-facial-digital-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about oral-facial-digital syndrome?

You may find the following resources about oral-facial-digital syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for oral-facial-digital syndrome?

  • dysplasia linguofacialis
  • OFDS
  • orodigitofacial dysostosis
  • orodigitofacial syndrome
  • orofaciodigital syndrome
  • oro-facio-digital syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about oral-facial-digital syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding oral-facial-digital syndrome?

autosomal ; autosomal recessive ; brachydactyly ; cell ; chromosome ; cleft palate ; clinodactyly ; cysts ; disability ; dysplasia ; frenula ; gene ; gums ; hypertelorism ; incidence ; inherited ; kidney ; mutation ; neurological ; palate ; polycystic kidney ; polydactyly ; protein ; recessive ; sex chromosomes ; syndactyly ; syndrome ; tissue ; X-linked dominant

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B. Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet. 2001 Mar;68(3):569-76. Epub 2001 Feb 13. (http://www.ncbi.nlm.nih.gov/pubmed/11179005?dopt=Abstract)
  • Gurrieri F, Franco B, Toriello H, Neri G. Oral-facial-digital syndromes: review and diagnostic guidelines. Am J Med Genet A. 2007 Dec 15;143A(24):3314-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17963220?dopt=Abstract)
  • Macca M, Franco B. The molecular basis of oral-facial-digital syndrome, type 1. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):318-25. doi: 10.1002/ajmg.c.30224. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19876934?dopt=Abstract)
  • Nowaczyk MJ, Zeesman S, Whelan DT, Wright V, Feather SA. Oral-facial-digital syndrome VII is oral-facial-digital syndrome I: a clarification. Am J Med Genet A. 2003 Dec 1;123A(2):179-82. (http://www.ncbi.nlm.nih.gov/pubmed/14598343?dopt=Abstract)
  • Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B; Oral-Facial-Digital Type I (OFDI) Collaborative Group. Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat. 2008 Oct;29(10):1237-46. doi: 10.1002/humu.20792. (http://www.ncbi.nlm.nih.gov/pubmed/18546297?dopt=Abstract)
  • Saal S, Faivre L, Aral B, Gigot N, Toutain A, Van Maldergem L, Destree A, Maystadt I, Cosyns JP, Jouk PS, Loeys B, Chauveau D, Bieth E, Layet V, Mathieu M, Lespinasse J, Teebi A, Franco B, Gautier E, Binquet C, Masurel-Paulet A, Mousson C, Gouyon JB, Huet F, Thauvin-Robinet C. Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I. Clin Genet. 2010 Mar;77(3):258-65. doi: 10.1111/j.1399-0004.2009.01290.x. Epub 2009 Oct 8. (http://www.ncbi.nlm.nih.gov/pubmed/19817772?dopt=Abstract)
  • Siebert JR. The oral-facial-digital syndromes. Handb Clin Neurol. 2008;87:341-51. doi: 10.1016/S0072-9752(07)87018-7. (http://www.ncbi.nlm.nih.gov/pubmed/18809032?dopt=Abstract)
  • Thauvin-Robinet C, Cossée M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y, Bieth E, Layet V, Parent P, David A, Goldenberg A, Mortier G, Héron D, Sagot P, Bouvier AM, Huet F, Cusin V, Donzel A, Devys D, Teyssier JR, Faivre L. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. J Med Genet. 2006 Jan;43(1):54-61. (http://www.ncbi.nlm.nih.gov/pubmed/16397067?dopt=Abstract)
  • Toriello HV. Are the oral-facial-digital syndromes ciliopathies? Am J Med Genet A. 2009 May;149A(5):1089-95. doi: 10.1002/ajmg.a.32799. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19396822?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2010
Published: October 27, 2014