Prenatal detection of X-linked ichthyosis by maternal serum screening for Down syndrome

Maternal serum unconjugated oestriol (uE3) was measured in 15,375 pregnancies during 2 years of second-trimester risk assessment for Down syndrome using biochemical markers. Very low levels of uE3 (< 0.1 MOM) were detected in 22 serum samples (0.14 per cent). Very low uE3 was associated with an adverse outcome in 13 pregnancies including fetal death and miscarriage (N = 11) anencephaly (N = 1), and Meckel-Gruber syndrome (N = 1). Dry scales on the skin appeared in the first year of life in four boys. From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X-linked ichthyosis. Very low uE3 levels in the second trimester are indicative of this disease in pregnancies with normal ultrasound findings.