Achondrogenesis Health Article

Definition

Achondrogenesis is a disorder in which bone growth is severely affected. The condition is usually fatal early in life.

General description

The syndrome achondrogenesis results from abnormal bone growth and cartilage formation. It is considered a lethal form of infantile dwarfism. Dwarfism is a condition that leads to extremely short stature. In achondrogenesis, the abnormalities in cartilage formation lead to abnormalities in bone formation. The lethality of the disorder is thought to result from difficulty breathing, probably due to having a very small chest. Achondrogenesis usually results in a stillborn infant or very early fatality. Achondrogenesis can be subdivided into type 1 and type 2. Type 1 can further be subdivided into type 1A and type 1B. Types 1A and 1B are distinguished by microscopic differences in the cartilage and cartilage-forming cells. Cartilage-forming cells (chondrocytes) are abnormal in type 1A, whereas the cartilage matrix itself is abnormal in type 1B.

Previously, health care professionals had recognized achondrogenesis types 3 and 4, but those classifications have been abandoned. Types 3 and 4 are now considered to be slight variations of type 2 achondrogenesis. Types 1A, 1B, and type 2 all have different genetic causes, and that is one factor supporting the current classification.

Synonyms

Synonyms for achondrogenesis include chondrogenesis imperfecta, hypochondrogenesis, lethal neonatal dwarfism, lethal osteochondrodysplasia, and neonatal dwarfism. Achondrogenesis type 1A is also known as Houston-Harris type, achondrogenesis type 1B is also known as Fraccaro type chondrogenesis, and achondrogenesis type 2 is also known as Langer-Saldino type achondrogenesis or type 3 or type 4 achondrogenesis.

Genetic profile

As previously mentioned, achondrogenesis is currently divided into three distinct subtypes: type 1A, type 1B, and type 2. It appears that each subtype is caused by mutations in different genes.

The gene for type 1A has not yet been isolated, but it does follow an autosomal recessive pattern of inheritance.

Type 1B follows an autosomal recessive pattern of inheritance as well, but the gene has been isolated. It is the diastrophic dysplasia sulfate transporter gene (DTDST), which is located on the long arm of chromosome 5 (5q32-q33 specifically). Abnormalities in the DTDST gene result in abnormal sulfation of proteins, which is thought to result in disease.

The severity of mutation determines which disorder the patient will have. The most severe of these disorders is type 1B. Since both type 1A and 1B follow autosomal recessive patterns of inheritance, the chance of parents having another child with the disorder after having the first child is 25% for both disorders.

Similar to achondrogenesis type 1B, achondrogenesis type 2 represents the most severe disorder of a group of disorders resulting from the mutation of a single gene—the collagen type 2 gene (COL2A1), located on the long arm of chromosome 12 (12q13.1-q13.3 specifically). In addition to its important role in development and growth, collagen type 2 plays an important structural role in cartilage and in the ability of cartilage to resist compressive forces. Type 2, however, does not follow an autosomal recessive pattern of inheritance. Most of the mutations that cause type 2 are new mutations, meaning they are not passed from parents to children. Also, most of these mutations are considered autosomal dominant. However, some family members of affected children may have the mutant gene without having the disease. This is not a classical pattern of dominance and implies the involvement of other genes in the disease process.

Demographics

Achondrogenesis is equally rare in males and females of all races in the United States. Although the exact incidence is unknown, one estimate places the incidence at 1 case in every 40,000 births.

Traits found in all subtypes of achondrogenesis

All infants with achondrogenesis share these characteristics: an extremely short neck, underdeveloped lungs, a protuberant abdomen, low birth weight, extremely short limbs (micromelia) and other skeletal abnormalities. The most defining feature of this condition is the extreme shortness of the limbs.

Additionally, fetuses with achondrogenesis may have the condition polyhydramnios, a condition in which there is too much fluid around the fetus in the amniotic sac, and/or fetal hydrops, a condition in which there is too much fluid in the fetal tissues and/or cavities. Infants with achondrogenesis are also often born in the breech position (hindquarters first).