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 serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support.

Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing.

Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis.

Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). 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, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive 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.

Achondrogenesis type 1A and type 1B are believed to be inherited in an autosomal recessive pattern. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition.

Infants with achondrogenesis inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

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 caused by a new (de novo) mutation and usually occurs in people with no history of the disorder in their family. There are rare cases of families who have had more than one pregnancy with achondrogenesis type 2. These cases are thought to occur because of mosaicism, which means that a portion of the DNA in a person's cells is different than the DNA in the rest of his/her body. Germline mosaicism occurs then a person's reproductive cells (sperm or egg) carry a mutation not found in the rest of the cells in the body. Somatic mosaicism occurs when a person has a some body cells that carry a mutation and some body cells that do not carry the mutation. Individuals with germline or somatic mosaicism are generally healthy and do not show signs of the disorder.

Achondrogenesis can be diagnosed during pregnancy by ultrasound as early as 12-14 weeks. At birth, this condition is suspected when the infant has extremely short underdeveloped arms and legs, short ribs and small chest, and short trunk. X-ray findings include underdeveloped skull, vertebrate and rib cage.

Genetic testing of the TRIP11, SLC26A2 and COL2A1 genes can be performed to confirm the diagnosis and determine the type of achondrogenesis.