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Greig cephalopolysyndactyly syndrome

Reviewed March 2006

What is Greig cephalopolysyndactyly syndrome?

Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability.

How common is Greig cephalopolysyndactyly syndrome?

This condition is very rare; its prevalence is unknown.

What are the genetic changes related to Greig cephalopolysyndactyly syndrome?

Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.

Different genetic changes involving the GLI3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormality—such as a large deletion or rearrangement of genetic material—in the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome.

Related Chromosome(s)

Changes involving this chromosome are associated with Greig cephalopolysyndactyly syndrome.

  • chromosome 7

Related Gene(s)

Changes in this gene are associated with Greig cephalopolysyndactyly syndrome.

  • GLI3

Can Greig cephalopolysyndactyly syndrome be inherited?

This condition is inherited in an autosomal dominant pattern, which means one altered or missing copy of the GLI3 gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation or chromosomal abnormality from one affected parent. Other cases occur in people with no history of the condition in their family.

Where can I find information about diagnosis or management of Greig cephalopolysyndactyly syndrome?

These resources address the diagnosis or management of Greig cephalopolysyndactyly syndrome and may include treatment providers.

  • Gene Review: Greig Cephalopolysyndactyly Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1446)
  • Genetic Testing Registry: Greig cephalopolysyndactyly syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265306)
  • MedlinePlus Encyclopedia: Polydactyly (http://www.nlm.nih.gov/medlineplus/ency/article/003176.htm)
  • MedlinePlus Encyclopedia: Syndactyly (image) (http://www.nlm.nih.gov/medlineplus/ency/imagepages/1763.htm)

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

You may find the following resources about Greig cephalopolysyndactyly 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 Greig cephalopolysyndactyly syndrome?

  • cephalopolysyndactyly syndrome
  • Greig cephalopolysyndactyly (GCPS) syndrome
  • Greig 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 Greig cephalopolysyndactyly syndrome?

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

What glossary definitions help with understanding Greig cephalopolysyndactyly syndrome?

autosomal ; autosomal dominant ; big toe ; cell ; chromosome ; cutaneous ; deletion ; developmental delay ; disability ; gene ; gene expression ; hallux ; hypertelorism ; inherited ; macrocephaly ; mutation ; ocular hypertelorism ; polydactyly ; prevalence ; protein ; rearrangement ; syndactyly ; syndrome

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

References

  • Debeer P, Peeters H, Driess S, De Smet L, Freese K, Matthijs G, Bornholdt D, Devriendt K, Grzeschik KH, Fryns JP, Kalff-Suske M. Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations. Am J Med Genet A. 2003 Jul 1;120A(1):49-58. (http://www.ncbi.nlm.nih.gov/pubmed/12794692?dopt=Abstract)
  • Gene Review: Greig Cephalopolysyndactyly Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1446)
  • Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet. 2005 Apr;76(4):609-22. Epub 2005 Feb 28. (http://www.ncbi.nlm.nih.gov/pubmed/15739154?dopt=Abstract)
  • Johnston JJ, Olivos-Glander I, Turner J, Aleck K, Bird LM, Mehta L, Schimke RN, Heilstedt H, Spence JE, Blancato J, Biesecker LG. Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet A. 2003 Dec 15;123A(3):236-42. (http://www.ncbi.nlm.nih.gov/pubmed/14608643?dopt=Abstract)
  • Kalff-Suske M, Wild A, Topp J, Wessling M, Jacobsen EM, Bornholdt D, Engel H, Heuer H, Aalfs CM, Ausems MG, Barone R, Herzog A, Heutink P, Homfray T, Gillessen-Kaesbach G, König R, Kunze J, Meinecke P, Müller D, Rizzo R, Strenge S, Superti-Furga A, Grzeschik KH. Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome. Hum Mol Genet. 1999 Sep;8(9):1769-77. (http://www.ncbi.nlm.nih.gov/pubmed/10441342?dopt=Abstract)
  • Kroisel PM, Petek E, Wagner K. Phenotype of five patients with Greig syndrome and microdeletion of 7p13. Am J Med Genet. 2001 Aug 15;102(3):243-9. (http://www.ncbi.nlm.nih.gov/pubmed/11484201?dopt=Abstract)
  • Wild A, Kalff-Suske M, Vortkamp A, Bornholdt D, König R, Grzeschik KH. Point mutations in human GLI3 cause Greig syndrome. Hum Mol Genet. 1997 Oct;6(11):1979-84. (http://www.ncbi.nlm.nih.gov/pubmed/9302279?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: March 2006
Published: October 20, 2014