Recurrence of achondrogenesis type II within the same family: evidence for germline mosaicism

Achondrogenesis type II is a lethal skeletal dysplasia caused by new dominant mutations within the type II collagen gene (COL2A1). Here we report on two pregnancies of a healthy, nonconsanguineous young couple. In the first pregnancy, severe micromelia and generalized edema were noted on ultrasound at 21 weeks' gestation. Clinical, radiological, and histological evaluation of the fetus after termination of the pregnancy showed typical findings of achondrogenesis type II. In the second pregnancy, fetal hygroma was noted at 11 weeks' gestation. Similar clinical, radiographic, and histologic findings were observed in the second fetus, suggesting the recurrence of achondrogenesis II within this family. Molecular analysis of genomic DNA extracted from amniotic cells of the second fetus revealed heterozygosity for a 1340G > A missense mutation (G316D) in the COL2A1 gene. This mutation was not found in the parents. Although, we could not evaluate the presence of this mutation in the first fetus, we strongly believe that our data are in favor of germline mosaicism as the most likely explanation for the recurrence of type II achondrogenesis in both sibs.