Congenital nephrotic syndrome: prenatal diagnosis and genetic counselling by estimation of aminotic-fluid and maternal serum alpha-fetoprotein.

Nine families in which a previous child had had congenital nephrotic syndrome (C.N.) sought genetic counselling and possible antenatal diagnosis of fetal disease. Maternal serum and amniotic-fluid alpha-fetoprotein (A.F.P.) assays were carried out between the 15th and 20th weeks of subsequent pregnancies. Seven women in whom A.F.P. concentrations were normal chose to continue pregnancy, and they were all delivered of a healthy child. Markedly raised amniotic A.F.P. concentrations were found in two cases; in one of these cases maternal serum-A.F.P. was also raised. These pregnancies were terminated, and electron microscopy of the fetal kidneys showed evidence of C.N. in the fetus--i.e., loss of foot processes and an increase in the mesangial matrix of the glomeruli. The outcomes of these at-risk pregnancies indicate that prenatal diagnosis and genetic counselling are possible in families with a history of C.N. The results also stress the importance of carefully examining fetal kidneys whenever amniotic-fluid A.F.P. concentration is raised in the absence of apparent malformations.