Signs and Symptoms
The term "campomelic" comes from Greek, meaning "bent limb." Affected individuals are typically born with bowing of the long bones in the legs, and they are occasionally born with bowing in the arms. Bowing can cause characteristic skin dimples to form over the curved bones, especially on the lower legs.
People with campomelic dysplasia usually also have short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs instead of 12, bone abnormalities in the neck and feet that are abnormally rotated (clubfeet). When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia.
Many people with campomelic dysplasia have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Approximately 75% of affected individuals with a typical male chromosome pattern (46,XY) have ambiguous genitalia or normal female genitalia. Internal reproductive organs may not correspond with the external genitalia; they can be male (testes), female (ovaries) or a combination of the two.
Affected individuals have distinctive facial features, including a small chin, prominent eyes and a flat face. They also have a large head compared to their body size. A particular group of physical features, called Pierre-Robin sequence, is common in people with campomelic dysplasia. Pierre-Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis) and a small lower jaw (micrognathia). People with campomelic dysplasia are often born with weakened cartilage that forms the upper respiratory tract. This abnormality, called laryngotracheomalacia, partially blocks the airway and causes difficulty breathing. Laryngotracheomalacia contributes to the poor survival of infants with campomelic dysplasia.
Only a few people with campomelic dysplasia survive past infancy. As these individuals age, they may develop an abnormal curvature of the spine (scoliosis) and other spine abnormalities that compress the spinal cord. People with campomelic dysplasia may also have short stature and hearing loss.
How common is campomelic dysplasia?
What genetic mutations cause campomelic dysplasia?
Mutations in or near the SOX9 gene cause campomelic dysplasia. The SOX9 gene provides instructions for making the SOX9 protein, which plays a critical role in the formation of many different tissues and organs during embryonic development. The protein regulates the activity of other genes, especially those that are important for development of the skeleton and reproductive organs. When the mutations within the SOX9 genes prevent the production of the SOX9 protein or result in a protein with impaired function, the result is campomelic dysplasia.
About 5% of cases are caused by chromosome abnormalities that occur around the SOX9 gene. These chromosome abnormalities disrupt regions of DNA that normally regulate the activity of the SOX9 gene. All of these genetic changes prevent the SOX9 protein from properly controlling the genes essential for normal development of the skeleton, reproductive system, and other parts of the body, causing the signs and symptoms of campomelic dysplasia.
How do people inherit campomelic dysplasia?
Campomelic dysplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in or near the SOX9 gene and occur in people with no history of the disorder in their family. Rarely, affected individuals inherit a chromosome abnormality from a parent who may or may not show mild signs and symptoms of campomelic dysplasia.