Cleidocranial dysplasia
Cleidocranial dysplasia is a rare genetic condition that primarily affects the development of bones and teeth. Individuals with this condition typically experience underdeveloped or absent collarbones, delayed skull maturation, and various dental abnormalities.
Overview
Cleidocranial dysplasia is a condition that primarily impacts the development of the skeletal system and teeth. The severity of signs and symptoms can vary widely, even among affected members of the same family.
Individuals with this condition typically 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 can even meet in the middle. Delayed maturation of the skull (cranium) is also characteristic, including delayed closing of the growth lines where skull bones meet (sutures) and larger than normal spaces (fontanelles) between skull bones, which are noticeable as "soft spots" on the heads of infants. While fontanelles normally close in early childhood, they may remain open throughout life in people with this disorder. Some affected individuals have extra pieces of bone called Wormian bones within their skull sutures.
Affected individuals are often shorter than other members of their family of the same age. Many also have short shoulder blades (scapulae) and an abnormal curvature of the spine. Typical facial features include:
- A wide, short skull
- A prominent forehead
- Wide-set eyes
- A flat nose
- A small upper jaw
People with cleidocranial dysplasia often 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. Due to a narrow pelvis that can prevent the passage of an infant's head, women with this condition have an increased risk of requiring a cesarean section during childbirth.
Dental abnormalities are highly common and may include:
- Delayed loss of primary (baby) teeth
- Delayed appearance of secondary (adult) teeth
- Unusually shaped, peg-like teeth
- Misalignment of the teeth and jaws (malocclusion)
- Other dental abnormalities, sometimes accompanied by cysts in the gums
In addition to skeletal and dental features, individuals with cleidocranial dysplasia may experience hearing loss and are prone to sinus and ear infections. Some young children may experience mild delays in developing motor skills like crawling and walking, but intelligence is unaffected.
Frequency
Cleidocranial dysplasia occurs in approximately 1 per million individuals worldwide. Because many affected individuals experience only mild signs and symptoms, the condition is likely underdiagnosed.
Causes
Cleidocranial dysplasia is usually caused by mutations in the RUNX2 gene. This gene provides instructions for producing a protein involved in the development and maintenance of teeth, bones, and cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development, most of which is later converted to bone through a process called ossification.
The RUNX2 protein is a transcription factor, meaning it binds to specific regions of DNA to help control the activity of particular genes. Researchers believe the RUNX2 protein acts as a "master switch," regulating several other genes involved in the development of teeth and the cells that build bones (osteoblasts).
Mutations in the RUNX2 gene reduce or eliminate the activity of the protein produced from one copy of the gene in each cell, decreasing the total amount of functional RUNX2 protein. This shortage interferes with the normal development of bones, cartilage, and teeth. In rare cases, individuals with a deletion of genetic material that includes RUNX2 and nearby genes may experience additional features, such as developmental delay.
In about 30 percent of individuals with cleidocranial dysplasia, no mutation in the RUNX2 gene has been identified. The cause of the condition in these individuals remains unknown.
Genes Associated with Cleidocranial Dysplasia
- RUNX2
Inheritance
This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit the mutation from a parent, who may be mildly affected and might not have been previously diagnosed. Other cases result from new mutations in people with no history of the disorder in their family.
Other Names for This Condition
- Cleidocranial dysostosis
- Dento-osseous dysplasia
- Marie-Sainton syndrome