achondrogenesis

Achondrogenesis is a rare, lethal skeletal dysplasia characterized by defective cartilage formation and markedly abnormal endochondral ossification, resulting in extreme micromelia and a severely underossified skeleton. Affected fetuses typically have short limbs, a relatively large head, and a narrow chest. Prenatal imaging may reveal reduced fetal ossification of the spine and skull.

There are two major forms. Achondrogenesis type I is autosomal recessive and involves mutations in genes other than COL2A1. Achondrogenesis type II is autosomal dominant and caused by mutations in COL2A1, which encodes type II collagen. The COL2A1-related form also underlies related conditions such as hypochondrogenesis, highlighting a spectrum of COL2A1-associated skeletal abnormalities. Both forms are usually lethal perinatally.

Diagnosis is based on clinical features and radiographs, with molecular genetic testing to confirm the subtype. Radiographs commonly show marked hypomineralization, especially of the skull and spine, with shortened, poorly ossified long bones and rib anomalies.

There is no cure. Management is supportive and includes counseling for families; prognosis remains poor with perinatal mortality common. Prenatal diagnosis enables early counseling and decision-making.