Hypochondrogenesis

What is hypochondrogenesis?

Hypochondrogenesis is a rare, severe disorder of bone growth. This condition is characterised by a small body, short limbs, and abnormal bone formation (ossification) in the spine and pelvis.

Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Bones in the skull appear normal, but the bones of the spine (vertebrae) and pelvic bones do not harden properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. The abdomen is enlarged, and affected infants may have a condition called hydrops foetalis in which excess fluid builds up in the body before birth.

As a result of these serious health problems, affected infants are usually born prematurely, are stillborn, or die shortly after birth from respiratory failure. Some infants have lived for a while, however, with intensive medical support. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related disorder that affects bone development.

How common is hypochondrogenesis?

Hypochondrogenesis and achondrogenesis, type 2 (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 births.

What genes are related to hypochondrogenesis?

Mutations in the COL2A1 gene cause hypochondrogenesis.

Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other tissues that form the body's supportive framework (connective tissues). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.

How do people inherit hypochondrogenesis?

Hypochondrogenesis is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is caused by new mutations in the COL2A1 gene and occurs in people with no history of the disorder in their family. This condition is not passed on to the next generation because affected individuals do not live long enough to have children.