Campomelic dysplasia

Synonyms

7

Overview

Campomelic dysplasia is a severe disorder that affects development of the skeleton, reproductive system, and other parts of the body. This condition is often life-threatening in the newborn period.

The term "campomelic" comes from the Greek words for "bent limb." Affected individuals are typically born with bowing of the long bones in the legs, and occasionally, bowing in the arms. Bowing can cause characteristic skin dimples to form over the curved bone, especially on the lower legs. People with campomelic dysplasia usually have short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs instead of 12, bone abnormalities in the neck, and inward- and upward-turning feet (clubfeet). These skeletal abnormalities begin developing before birth and can often be seen on ultrasound. 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 percent 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; the internal organs can be male (testes), female (ovaries), or a combination of the two. For example, an individual with female external genitalia may have testes or a combination of testes and ovaries.
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 withcampomelic 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 withcampomelic 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.

 

Symptoms

Individuals with campomelic dysplasia 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 bone, especially on the lower legs. People with campomelic dysplasia also usually 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 (club feet). 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 percent 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.

Symptoms:

  • Abnormal vertebral ossification
  • Abnormality of bone mineral density
  • Abnormality of the fibula
  • Abnormality of the hip bone
  • Abnormality of the ribs
  • Abnormality of the tibia
  • Bowing of the long bones
  • Laryngomalacia
  • Macrocephaly
  • Malar flattening
  • Narrow chest
  • Recurrent fractures
  • Respiratory insufficiency
  • Scoliosis
  • Short neck
  • Sprengel anomaly
  • Tracheomalacia
  • Growth deficiency
  • Retarded osseous maturation
  • Large head
  • Large brain
  • Gross cellular disorganization of the brain

Causes

It is caused by mutations in the SOX9 gene and is inherited in an autosomal dominant pattern, although most cases result from a new mutation in the affected individual. 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, especially those that are important for development of the skeleton and reproductive organs. SOX9 gene plays a role in bone formation and testes development. Genes are units of hereditary material found on chromosomes, which are passed from a parent to a child through the egg and sperm. The information contained in genes is responsible for the development of all the cells and tissues of the body.

Diagnosis

The most characteristic sign of campomelic dysplasia is the marked anterior bowing of the long bones, particularly of femur and tibia. Severe angulation may mimic fractures. Other sonographic features that are commonly present include, growth restriction, bell-shaped narrow chest, eleven pair of ribs, hypoplasia of the mid-thoracic vertebral bodies, fibula, and scapula, scoliosis, shortness of the limbs, talipes equinovarus, tracheobronchomalacia, flat and small face, high forehead with prominent occiput, low nasal bridge, micrognathia, cleft of the soft palate, hypertelorism, low-set and malformed ears, hydrocephalus, and ambiguous genitalia.

Prognosis

Almost all result in neonatal or infant death, due to respiratory complications. Some survivors, including a boy alive at 17 years, have been reported.

Treatment

Treatment typically includes multiple surgeries to correct some of the above-mentioned abnormalities. When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia.

 

Resources

  • NIH
  • Genetics Home Reference