Achondrogenesis

What is achondrogenesis?

Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of their serious health problems, infants with achondrogenesis are usually born prematurely, are stillborn, or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support.

Researchers have described at least two forms of achondrogenesis, designated as type 1B and type 2. These types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. Other types of achondrogenesis may exist, but they have not been characterized or their cause is unknown.

Achondrogenesis, type 1B is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may be rotated inward. Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).

Infants with achondrogenesis, type 2 have short arms and legs, a small chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of bone formation (ossification) in the spine and pelvis. Typical facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.

How common is achondrogenesis?

Achondrogenesis, type 1B is a rare genetic disorder; its incidence is unknown. Achondrogenesis, type 2 and hypochondrogenesis (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 births.

What genes are related to achondrogenesis?

Mutations in the COL2A1 and SLC26A2 genes cause achondrogenesis.

Achondrogenesis, type 1B is the most severe condition in a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene disrupt the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of achondrogenesis, type 1B.

Achondrogenesis, type 2 is one of several skeletal 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 achondrogenesis?

Achondrogenesis, type 1B is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Achondrogenesis, type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is almost always caused by new mutations in the COL2A1 gene and typically 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.