SNP Shot: Genomic Insights

Campomelic dysplasia is a serious condition impacting the development of the skeletal system, reproductive organs, and other bodily structures. Newborns with this disorder often face life-threatening complications.

The name "campomelic" originates from Greek, meaning "bent limb." A common characteristic is the bowing of the long bones in the legs at birth, sometimes also affecting the arms. This bowing can create noticeable skin indentations over the curved bone, especially in the lower legs. Individuals with campomelic dysplasia typically have short legs, hip dislocations, underdeveloped shoulder blades, 11 pairs of ribs instead of the usual 12, spinal abnormalities in the neck, and clubfeet. These skeletal problems begin before birth and are often visible on ultrasound scans. Acampomelic campomelic dysplasia is diagnosed when individuals exhibit other features of the disorder without the bowed limbs.

Many individuals with campomelic dysplasia exhibit ambiguous genitalia, meaning their external genitalia do not clearly appear male or female. In roughly 75% of affected individuals with a typical male chromosome pattern (46,XY), the external genitalia are ambiguous or appear as normal female genitalia. The internal reproductive organs may not match the external genitalia, and can be male (testes), female (ovaries), or a combination of both. For example, an individual with female external genitalia could possess testes or a combination of testes and ovaries internally.

Individuals with campomelic dysplasia often share distinctive facial features, including a small chin, prominent eyes, and a flattened facial appearance. They also tend to have a disproportionately large head relative to their body size. The Pierre Robin sequence, a group of physical features, is frequently observed in people with campomelic dysplasia. This sequence includes a cleft palate, glossoptosis (a tongue positioned further back than normal), and micrognathia (a small lower jaw). Furthermore, infants with campomelic dysplasia are frequently born with weakened cartilage in the upper respiratory tract, a condition called laryngotracheomalacia. This condition obstructs the airway, leading to breathing difficulties and contributing to the high mortality rate in infants with campomelic dysplasia.

Few individuals with campomelic dysplasia survive beyond infancy. As they get older, they may develop scoliosis (an abnormal curvature of the spine) and other spinal issues that compress the spinal cord. Short stature and hearing loss can also occur in people with campomelic dysplasia.

Inheritance:

Campomelic dysplasia follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene in each cell is sufficient to cause the disorder. Most cases arise from new mutations in or near the SOX9 gene and occur in individuals with no prior family history of the condition. In rare instances, affected individuals inherit a chromosomal abnormality from a parent who may or may not exhibit mild symptoms of campomelic dysplasia.