Campomelic dysplasia
Campomelic dysplasia is a severe, often life-threatening genetic disorder that profoundly affects the development of the skeleton, reproductive system, and other parts of the body.
Overview
Campomelic dysplasia is a severe disorder affecting the development of the skeleton, reproductive system, and other body systems. The term "campomelic" is derived from the Greek words for "bent limb." This condition is often life-threatening during the newborn period, and only a few affected individuals survive past infancy.
Symptoms & Clinical Features
Skeletal abnormalities begin developing before birth and can often be detected via ultrasound. Characteristic features include:
- Bowing of the long bones in the legs, and occasionally in the arms, which can cause skin dimples to form over the curved bone (especially on the lower legs)
- Short legs and dislocated hips
- Underdeveloped shoulder blades
- 11 pairs of ribs instead of the normal 12
- Bone abnormalities in the neck
- Inward- and upward-turning feet
- Short stature and abnormal curvature of the spine as survivors age, which can compress the spinal cord
When individuals have features of this disorder but do not present with bowed limbs, the condition is referred to as acampomelic campomelic dysplasia.
Reproductive Abnormalities
Approximately 75 percent of affected individuals with a typical male chromosome pattern (46,XY) have normal female genitalia or genitalia that do not look clearly male or clearly female (ambiguous genitalia). Internal reproductive organs may not correspond with external genitalia; internal organs can be male (testes), female, or a combination of both (such as an individual with female external genitalia having testes or a mix of testes and ovaries).
Facial and Respiratory Features
Affected individuals typically have distinctive facial features, including a small chin, prominent eyes, a flat face, and a large head compared to body size. A specific group of physical features known as Pierre Robin sequence is common, which includes:
- An opening in the roof of the mouth (cleft palate)
- A tongue placed further back than normal (glossoptosis)
- A small lower jaw (micrognathia)
Infants are also often born with weakened cartilage in the upper respiratory tract, a condition called laryngotracheomalacia. This partially blocks the airway, causing breathing difficulties and contributing to the poor survival rate of infants with the disorder. Hearing loss is also common among survivors.
Frequency
The exact prevalence of campomelic dysplasia is uncertain, with estimates ranging from 1 in 40,000 to 1 in 200,000 people.
Causes & Genetic Factors
Mutations in or near the SOX9 gene cause campomelic dysplasia. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX9 protein regulates the activity of other genes, particularly those important for skeletal and reproductive organ development.
Most cases are caused by mutations within the SOX9 gene that prevent the production of the SOX9 protein or result in an impaired protein. About 5 percent of cases are caused by chromosome abnormalities occurring near the SOX9 gene, which tend to be milder. 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.
Associated Gene
- SOX9
Inheritance
Campomelic dysplasia is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations (de novo) in or near the SOX9 gene and occur in people with no family history of the condition. Rarely, affected individuals inherit the mutation from a parent, who may or may not show mild signs and symptoms of the disorder.
Other Names for This Condition
- Campomelic dwarfism
- Campomelic syndrome
- Camptomelic dysplasia