What is cleidocranial dysplasia?
Cleidocranial dysplasia is a condition that primarily affects the development
of the bones and teeth.
What are the symptoms and signs of cleidocranial dysplasia?
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.
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 treatment for cleidocranial dysplasia?
These resources address the management of cleidocranial dysplasia and may
include treatment providers.
- Gene Review:
Cleidocranial Dysplasia
What other names do people use for cleidocranial dysplasia?
- cleidocranial dysostosis
- Marie-Sainton syndrome
SOURCE: Genetics Home Reference; U.S. National Library of Medicine