Achondrogenesis is a number of disorders that are the most severe form of

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

chondrodysplasia Osteochondrodysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro"). Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Non ...

(malformation of

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

s and

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

). 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 Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term i ...

, 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 three forms of achondrogenesis, designated as Achondrogenesis type 1A,

achondrogenesis type 1B Achondrogenesis, type 1B is a severe autosomal recessive skeletal disorder, invariably fatal in the perinatal period.
Achondrogenesis ...

and

achondrogenesis type 2 Achondrogenesis, type 2 results in short arms and legs, a small chest with short ribs, and underdeveloped lungs at birth. Achondrogenesis, type 2 is a subtype of collagenopathy, types II and XI. This condition is also associated with a lack of bon ...

. 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 1A is caused by a defect in the microtubules of the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

. In mice, a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210), resulted in defects similar to the human disease. When their DNA was sequenced, human patients with achondrogenesis type 1A also had loss-of-function mutations in GMAP-210. GMAP-210 moves proteins from the endoplasmic reticulum to the Golgi apparatus. Because of the defect, GMAP-210 is not able to move the proteins, and they remain in the endoplasmic reticulum, which swells up. The loss of Golgi apparatus function affects some cells, such as those responsible for forming bone and cartilage, more than others.Lethal skeletal dysplasia in mice and humans lacking the GolginGMAP-210, Patrick Smits et al., N Engl J Med, 362:206, Jan. 21, 2010 Achondrogenesis type 1B is caused by a similar mutation in SLC26A2, which encodes a sulfate transporter. Achondrogenesis, type 2 is one of several skeletal disorders caused by mutations in the ''

COL2A1 Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen. Function This ge ...

'' gene. Achondrogenesis, type 2 and

hypochondrogenesis Hypochondrogenesis is a severe genetic disorder causing malformations of bone growth. The condition is characterized by a short body and limbs and abnormal bone formation in the spine and pelvis. Hypochondrogenesis is a subtype of collagenopathy, ...

(a similar skeletal disorder) together affect 1 in 40,000 to 60,000 births.

References

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External links

{{Osteochondrodysplasia Congenital disorders