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Genetics Home Reference: your guide to understanding genetic conditions
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Cleidocranial dysplasia

Reviewed January 2008

What is cleidocranial dysplasia?

Cleidocranial dysplasia is a condition that primarily affects the development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family.

Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones (clavicles). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases the shoulders can be made to meet in the middle of the body. Delayed closing of the spaces between the bones of the skull (fontanels) is also characteristic of this condition. The fontanels usually close in early childhood, but may remain open into adulthood in people with this disorder.

Affected individuals may be 3 to 6 inches shorter than other members of their family, and may have short, tapered fingers and broad thumbs; short forearms; flat feet; knock knees; and an abnormal curvature of the spine (scoliosis). Characteristic facial features may include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw.

Individuals with cleidocranial dysplasia may have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age. Women with cleidocranial dysplasia have an increased risk of requiring a cesarean section when delivering a baby, due to a narrow pelvis preventing passage of the infant's head.

Dental abnormalities seen in cleidocranial dysplasia may include delayed loss of the primary (baby) teeth; delayed appearance of the secondary (adult) teeth; unusually shaped, peg-like teeth; misalignment of the teeth and jaws (malocclusion); and extra teeth, sometimes accompanied by cysts in the gums.

In addition to skeletal and dental abnormalities, people with cleidocranial dysplasia may have hearing loss and be prone to sinus and ear infections. Some young children with this condition are mildly delayed in the development of motor skills such as crawling and walking, but intelligence is unaffected.

How common is cleidocranial dysplasia?

Cleidocranial dysplasia occurs in approximately 1 per million individuals worldwide.

What genes are related to cleidocranial dysplasia?

The RUNX2 gene provides instructions for making a protein that is involved in bone and cartilage development and maintenance. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the RUNX2 protein acts as a "master switch," regulating a number of other genes involved in the development of cells that build bones (osteoblasts).

Some mutations change one protein building block (amino acid) in the RUNX2 protein. Other mutations introduce a premature stop signal that results in an abnormally short protein. Occasionally, the entire gene is missing.

These genetic changes reduce or eliminate the activity of the protein produced from one copy of the RUNX2 gene in each cell, decreasing the total amount of functional RUNX2 protein. This shortage of functional RUNX2 protein interferes with normal bone and cartilage development, resulting in the signs and symptoms of cleidocranial dysplasia. In rare cases, affected individuals may experience additional, unusual symptoms resulting from the loss of other genes near RUNX2.

In about one-third of individuals with cleidocranial dysplasia, no mutation in the RUNX2 gene has been found. The cause of the condition in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with cleidocranial dysplasia.

  • RUNX2

How do people inherit cleidocranial dysplasia?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of cleidocranial dysplasia?

These resources address the diagnosis or management of cleidocranial dysplasia and may include treatment providers.

  • Gene Review: Cleidocranial Dysplasia (http://www.ncbi.nlm.nih.gov/books/NBK1513/)
  • Genetic Testing Registry: Cleidocranial dysostosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0008928)
  • MedlinePlus Encyclopedia: Cleidocranial dysostosis (http://www.nlm.nih.gov/medlineplus/ency/article/001589.htm)

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

You may find the following resources about cleidocranial dysplasia 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 cleidocranial dysplasia?

  • cleidocranial dysostosis
  • Marie-Sainton 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 cleidocranial dysplasia?

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

What glossary definitions help with understanding cleidocranial dysplasia?

amino acid ; autosomal ; autosomal dominant ; bone density ; brachycephaly ; cartilage ; cell ; cysts ; DNA ; dysplasia ; gene ; gums ; hypertelorism ; motor ; mutation ; osteopenia ; osteoporosis ; pelvis ; protein ; scoliosis ; sinus ; syndrome ; transcription ; transcription factor

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

References

  • Cohen MM Jr. The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A. 2006 Dec 1;140(23):2646-706. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17103447?dopt=Abstract)
  • Gene Review: Cleidocranial Dysplasia (http://www.ncbi.nlm.nih.gov/books/NBK1513/)
  • Hermanns P, Lee B. Transcriptional dysregulation in skeletal malformation syndromes. Am J Med Genet. 2001 Winter;106(4):258-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11891677?dopt=Abstract)
  • Lo Muzio L, Tetè S, Mastrangelo F, Cazzolla AP, Lacaita MG, Margaglione M, Campisi G. A novel mutation of gene CBFA1/RUNX2 in cleidocranial dysplasia. Ann Clin Lab Sci. 2007 Spring;37(2):115-20. (http://www.ncbi.nlm.nih.gov/pubmed/17522365?dopt=Abstract)
  • OMIM: CLEIDOCRANIAL DYSPLASIA (http://omim.org/entry/119600)
  • Otto F, Kanegane H, Mundlos S. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat. 2002 Mar;19(3):209-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11857736?dopt=Abstract)
  • Pal T, Napierala D, Becker TA, Loscalzo M, Baldridge D, Lee B, Sutphen R. The presence of germ line mosaicism in cleidocranial dysplasia. Clin Genet. 2007 Jun;71(6):589-91. (http://www.ncbi.nlm.nih.gov/pubmed/17539909?dopt=Abstract)
  • Rice DP. Craniofacial anomalies: from development to molecular pathogenesis. Curr Mol Med. 2005 Nov;5(7):699-722. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16305494?dopt=Abstract)
  • Schroeder TM, Jensen ED, Westendorf JJ. Runx2: a master organizer of gene transcription in developing and maturing osteoblasts. Birth Defects Res C Embryo Today. 2005 Sep;75(3):213-25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16187316?dopt=Abstract)
  • Segal N, Puterman M. Cleidocranial dysplasia - review with an emphasis on otological and audiological manifestations. Int J Pediatr Otorhinolaryngol. 2007 Apr;71(4):523-6. Epub 2007 Jan 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17239447?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: January 2008
Published: July 7, 2014