Achondroplasia

ACHONDROPLASIA (ACH) is a rare genetic disorder caused by a change (mutation) in gene in the fibroblast growth factor receptor 3 (FGFR3) gene that prevents the changing of cartilage (primarily in the long bones – arms and legs) to bone. This mutation occurs in utero. Although it is rare, ACH is the most common form of dwarfism (skeletal dysplasia). It occurs in 1 in 25,000 births. 80% of children born with the condition are born to parents without the condition and have no familial history of the condition.

Bones begin growing before birth (in utero) and keep growing until adulthood. The process happens in the bones’ growth plates, where the body makes cartilage that is then replaced by bone. Chondrocytes (cells in the cartilage) line up to form new bone. This process is called endochondral ossification and happens in almost all the bones of the body. Receptors in chondrocytes control the process by sending out and receiving signals.

Some signals, like the signals from FGFR3 receptors, tell the bones to slow down growth. Others, like the signals from NPRB receptors (natriuretic peptide receptor B), block those signals and allow bones to grow. FGFR3 receptors are usually only “turned on” when the body needs to stop changing cartilage into bone. In ACH, a change in the structure of the FGFR3 gene causes the body to continuously send out signals to slow bone growth. Because FGFR3 receptors are always “turned on,” the signals to slow bone growth are stronger than the signals that tell bones to grow (which come from the NPRB receptors). As a result, the chondrocytes have trouble lining up to form new bone, impairing bone growth.