Cleidocranial dysplasia is an autosomal dominant genetic disorder that influences the development of bones, such as the shoulders, collarbones, spine, jaw and teeth. As with most genetic disorders, signs and symptoms of cleidocranial dysplasia can vary in affected individuals. The gene, RUNX2, when mutated is the cause of this disorder. It is estimated that cleidocranial dysplasia occurs in roughly 1 in 1,000,000 people worldwide.
Signs and Symptoms
Patients with cleidocranial dysplasia tend to have developmentally delayed collarbones that result in narrow and sloping shoulders. In severe cases, shoulders can be brought together in front of the body. There can be a delayed closure of the fontanels, or bones of the skull, during and after pregnancy. The fontanels usually close on their own but can remain open well into adulthood.
Other signs in the limbs and the face also occur. Individuals may also be 3 to 6 inches shorter than their average peers or have short fingers and forearms. More severe cases have an abnormal curvature of the spine. Facial features include a short skull, large forehead, flat nose, wide-eyes and a decreased upper jaw. Abnormalities in the bone also decrease bone density which some individuals may develop osteoporosis. With osteoporosis, bones become brittle and may break more frequently.
Additionally, patients with cleidocranial dysplasia may experience hearing loss and are more susceptible to sinus and ear infections. Intelligence is generally unaffected with this disorder, but motor skills functionality may be decreased.
The onset of roughly 60 percent cleidocranial dysplasia starts mainly from a mutation of the RUNX2 gene located on chromosome 6. The RUNX2 gene makes a protein that is known to help with bone and cartilage development. It is believe that this protein has a primary role in regulating other genes involved in developing cells that build bones. Mutations can change a single amino acid by deletion/insertion, make an ineffective protein, or delete the entire RUNX2 gene.The other 40 percent of cleidocranial dysplasia patients with a RUNX2 mutation have unknown causes.
Cleidocranial dysplasia has an autosomal dominant inheritance pattern. This means that the mutation occurs on a non-sexual chromosome, in this case, chromosome 6. Dominant means that individuals only need one mutated gene to get the disorder. If an affected mother has a child with an unaffected father, the chances of the child getting cleidocranial dysplasia are 50 percent.
Diagnosis and Treatment
The diagnosis of cleidocranial dysplasia can be done based on the physical appearance of the individual, or by examining the family history of the individual in question. A more thorough investigation includes the sequencing of the RUNX2 gene which is known of cause around 60% of all cleidocranial dysplasia cases.
Like the majority of autosomal dominant disorders, there is no known cure for cleidocranial dysplasia. However, an audiologist should continually check for hearing loss and an oral surgeon should moniter abnormal teeth activity. There are no known studies performed trying to find preventativies to decrease the possible onset.