Achondrogenesis

Achondrogenesis (Orphanet code 932) is a group of severe, lethal skeletal dysplasias characterized by extremely short limbs, a small body, and profound deficiency of bone ossification. It represents one of the most severe forms of congenital chondrodysplasia. There are two major subtypes: Achondrogenesis type 1 (which includes type 1A, also known as Houston-Harris type, and type 1B, also known as Fraccaro type) and Achondrogenesis type 2 (Langer-Saldino type). Type 1A is caused by mutations in the TRIP11 gene, type 1B by mutations in the SLC26A2 (DTDST) gene, and type 2 by mutations in the COL2A1 gene encoding type II collagen. The condition profoundly affects the skeletal system, with severe micromelia (extremely short limbs), a narrow thorax, a disproportionately large head with a soft skull, and marked deficiency of vertebral body and long bone ossification visible on radiographs. Affected infants typically have a short trunk, a prominent abdomen, and soft tissue edema (hydrops). The rib cage is extremely small, leading to pulmonary hypoplasia. Other features may include polyhydramnios during pregnancy and fetal hydrops. The condition is almost invariably lethal, with most affected infants being stillborn or dying shortly after birth due to respiratory failure. There is currently no curative treatment for achondrogenesis. Management is supportive and palliative. Prenatal diagnosis is possible through ultrasound examination, which may reveal severe limb shortening, poor ossification, and hydrops as early as the second trimester. Molecular genetic testing can confirm the diagnosis and specific subtype, which is important for accurate genetic counseling regarding recurrence risk, as the inheritance pattern differs between subtypes.

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