What are the other Names for this Condition? (Also known as/Synonyms)

• Cleidocranial-Pubic Dysostosis
• Marie-Sainton Disease
• Pelvicocleidocranial Dysplasia

What is Cleidocranial Dysostosis? (Definition/Background Information)

• Cleidocranial Dysostosis (CCD) is an extremely uncommon genetic disorder that is characterized by several abnormalities that involve the skull, teeth, collarbone (clavicle), and spinal cord. Most of the signs and symptoms are apparent at birth (congenital presentation); prominent ones being skull deformations and forward drooping shoulders
• It is reported that Cleidocranial Dysostosis may be caused by an abnormality on the RUNX2 gene. In many cases, the disorder is inherited, and so a positive family history is a risk factor for the same. In some, the disorder develops as the result of a new mutation (sporadic event)
• Cleidocranial Dysostosis is an incurable disorder, although the signs and symptoms may be adequately managed through suitable treatments, which may include use of hearing aids, surgical procedures, speech and language development, etc.
• A prevention of Cleidocranial Dysostosis includes genetic counseling for those with a history of the disorder (prior to planning for a child). The prognosis for Cleidocranial Dysostosis is usually favorable as the associated bone abnormalities generally pose severe health issues and complications

Who gets Cleidocranial Dysostosis? (Age and Sex Distribution)

• Cleidocranial Dysostosis is a very rare congenital disorder (manifested at birth); the signs and symptoms are generally present throughout the individual’s life
• The incidence rate of the disorder is about 1 in 1,000,000 births
• Both males and females may be affected
• Worldwide, all races and ethnic groups may be affected

What are the Risk Factors for Cleidocranial Dysostosis? (Predisposing Factors)

The predisposing factors for Cleidocranial Dysostosis include:

• Having a parent with Cleidocranial Dysostosis
• Having parents that are closely blood related (consanguineous) can significantly increase the risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cleidocranial Dysostosis? (Etiology)

Cleidocranial Dysostosis is a genetic disorder causing several birth defects due to a gene abnormality. The involved gene is RUNX2 (also termed CBFA1 gene) that is located on chromosome 6p21 (on the short arm of chromosome 6 at band p21).

• In nearly two-thirds of the cases, the disorder is inherited as an autosomal dominant trait (from one parent)
• Cleidocranial Dysostosis may also be the result of a new genetic mutation (sporadic occurrence), which is observed in the remaining one-third of the cases

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Cleidocranial Dysostosis?

The signs and symptoms of Cleidocranial Dysostosis may vary from one individual to another and can be mild or severe. These may include:

• Skull deformation due to premature closing of soft spots (fontanels) of the head and fibrous joints where the bones of the skull meet
• Abnormal facial features such as:
  • Prominent forehead and chin
  • Abnormally wide face
  • Small upper jaw (hypoplasia)
  • Bulging skull cap
  • Flat nose
  • Failure of lower jaw bones to fuse to one another
• Dental abnormalities including:
  • Delayed tooth eruption
  • Absence or reduced development of teeth
  • Underdeveloped enamel 
  • Extra teeth
  • Cysts which can develop around unerupted or displaced teeth
  • High-arch palate or cleft palate (hole in roof of the mouth)
• Sinus infections
• Partial or complete loss of hearing
• Upper respiratory complications
• Shoulders that droop forward due to partial or complete absence of collarbones; small shoulder blades
• Abnormal musculature around the shoulders allowing for a wide range of shoulder motion
• Widened pelvic joint; delayed pubic bone growth
• Thigh bones angle towards the center of the body (coxa vara) or thigh bones angle away from the center of the body (coxa valga) causing a hip deformation
• Knees angle inward and touch due to curvature in upper thigh bone (genu valgum)
• Short stature

How is Cleidocranial Dysostosis Diagnosed?

A diagnosis of Cleidocranial Dysostosis is made by the following observations and tests:

• A careful physical examination and evaluation of the affected individual’s medical history
• Assessment of the presenting signs and symptoms
• Blood tests, as needed
• X-ray studies of the affected region
• CT and MRI scans of the affected regions, as necessary
• Prenatal testing in pregnant women
• Molecular genetic testing, if available

A differential diagnosis to rule-out the following conditions is necessary prior to making a definitive diagnosis:

• Hajdu-Cheney syndrome
• Mandibuloacral dysplasia
• Osteogenesis imperfecta
• Pyknodysostosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cleidocranial Dysostosis?

The possible complications of Cleidocranial Dysostosis include:

• Emotional stress
• Permanent deafness
• Upper respiratory complications
• Recurrent sinus infections
• Increased susceptibility to shoulder dislocations
• Difficulty eating and speaking due to jaw abnormalities
• Spondylosis and spondylolisthesis
• Spina bifida
• Abnormal spine curvature (scoliosis and kyphosis)
• Decreased quality of life

How is Cleidocranial Dysostosis Treated?

The treatment measures for Cleidocranial Dysostosis may include:

• Protective headgear worn on the skull until the bones close
• Surgery to repair cleft palate and other bone abnormalities
• Hearing evaluations and appropriate hearing enhancement devices
• Symptoms such as sleep apnea, recurring ear infections, or recurrent sinus infections should be regularly monitored and appropriately treated
• Speech and language development with a speech pathologist
• Use of braces and/or invasive measures for spinal abnormalities, as needed
• Physical therapy and rehabilitation

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

How can Cleidocranial Dysostosis be Prevented?

Presently, Cleidocranial Dysostosis may not be preventable since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child

Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders.

What is the Prognosis of Cleidocranial Dysostosis? (Outcomes/Resolutions)

The prognosis of Cleidocranial Dysostosis is dependent upon the severity of the signs and symptoms and associated complications, if any.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• The associated bone abnormalities and other symptoms may get better with treatment and as the child gets older
• Intelligence and life expectancy is usually not affected in Cleidocranial Dysostosis

Additional and Relevant Useful Information for Cleidocranial Dysostosis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/