Cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is typically caused by changes (mutations) in the RUNX2 gene. This gene gives the body instructions to make a protein used in the development and maintenance of bone and cartilage.

Researchers believe that the RUNX2 protein acts like a "switch" that regulates other genes involved in the development of cells that build bones (osteoblasts). Mutations in the RUNX2 gene result in a shortage of normal protein, which in turn affects normal bone and cartilage development.

In some cases, no mutation or genetic abnormalities affecting the RUNX2 gene are found. The cause of the condition in these cases is currently unknown.

A person with features of cleidocranial dysplasia (CCD) or any other skeletal dysplasia should be referred to an orthopedist. If the doctor suspects a diagnosis of CCD, a skeletal survey (series of X-rays) should be ordered. The skeletal survey should include specific X-rays of the skull and thorax (chest); pelvis; lumbar spine (lower back); and long bones, hands, and feet.

Genetic testing of the RUNX2 gene, the only gene known to cause CCD, can be considered to confirm the diagnosis. This is particularly if the signs and symptoms found in the physical exam and X-rays do not meet the diagnostic criteria.

People with uncommon features of CCD and developmental delay may have another type of genetic testing called chromosomal microarray (CMA) to look for small missing pieces of chromosomes (microdeletions) or small extra pieces (microduplications) that involve the RUNX2 gene. If CMA does not confirm the diagnosis and CCD is still strongly suspected, a karyotype (organized chromosome picture) may still be considered to look for rearrangements of genetic material.

During a pregnancy, a fetus at risk can be tested for CCD if the genetic cause of the condition has already been identified in a family member. This is called prenatal diagnosis. This can be done by testing the DNA of fetal cells obtained by amniocentesis (in the 2nd trimester) or chorionic villus sampling (in the 1st trimester).

CCD may also be diagnosed in a pregnancy by an ultrasound of the fetus of an affected parent. CCD may be apparent on ultrasound as early as 14 weeks' gestation. The most common features seen on ultrasound are abnormal collarbones (clavicles), which are either very short, partially absent, or totally absent.

A number of other conditions share some characteristics with CCD. You can read about these conditions and their features on the GeneReviews website by clicking here.

Cleidocranial dysplasia is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

There is nothing a parent can do before, during, or after a pregnancy to cause cleidocranial dysplasia in a child.

There is no specific treatment for cleidocranial dysplasia (CCD), and management is based on each person's symptoms. Most people with CCD need dental care due to various dental abnormalities. If bone density is below normal, supplements of calcium and vitamin D may be needed, and preventive treatment for osteoporosis may be started at a young age. Those with frequent ear infections may need ear tubes. Severe defects of the cranial vault (space in the skull occupied by the brain) should be protected by wearing helmets during high-risk activities. Surgery may be needed to correct any of various skeletal (bone) abnormalities.