Cleidocranial Dysplasia Explained

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.

What Causes Cleidocranial dysplasia

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.

Cleidocranial dysostosis is caused by an abnormal gene. It is passed down through families as an autosomal dominant trait. That means you only need to get the abnormal gene from one parent in order for you to inherit the disease.

Cleidocranial dysostosis is a congenital condition, which means it is present from before birth. The condition affects girls and boys equally.

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.

Symptoms of Cleidocranial dysplasia

People with cleidocranial dysostosis have a jaw and brow area that sticks out. The middle of their nose (nasal bridge) is wide.

The collar bones may be missing or abnormally developed. This pushes the shoulders together in front of the body.

Primary teeth do not fall out at the expected time. Adult teeth may develop later than normal, and an extra set of adult teeth grow in. This causes the normal teeth to become crooked.

The condition does not affect a person’s intelligence.

Other symptoms can include:

  • Ability to touch shoulders together in front of body
  • Delayed closure of fontanelles (“soft spots”)
  • Loose joints
  • Prominent forehead (frontal bossing)
  • Short forearms
  • Short fingers

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.

Exams and Tests

There is often a family history of cleidocranial dysostosis. X-rays are usually taken and may show:

  • Undergrowth of the collarbone
  • Undergrowth of the shoulder blade
  • Failure of the area in the front of the pelvis bone to close

Treatment

There is no specific treatment for the bone problems. An oral surgeon should monitor teeth regularly. An otologist should check for hearing problems.

Outlook (Prognosis)

The bone symptoms usually cause few problems. Appropriate dental care is important.

Possible Complications

Complications include dental problems and shoulder dislocations.

What other names do people use for cleidocranial dysplasia

  • Cleidocranial dysostosis
  • Marie-Sainton syndrome

When to Contact a Medical Professional

Call your health care provider if you have a family history of cleidocranial dysostosis and are planning to have a child. Also call if you have a child with similar symptoms.

Prevention

Genetic counseling is appropriate if a person with a family or personal history of cleidocranial dysostosis is planning to have children.

How is it diagnosed

Diagnosis is based on the clinical and radiographic findings, such as typical characteristics being visible on X-ray. Genetic testing can confirm the presence of a mutation in RUNX2.

Source & More Info: Medline Plus and Genetics Home Reference

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