Low maternal serum estriol as a marker for steroid sulfatase deficiency

Abstract

Maternal serum screening began in the early 1980's with the evaluation of alpha-feto-protein (AFP) levels to identify pregnancies at an increased risk for neural tube defects and later for Down syndrome. Elevated levels of AFP have been found to be markers for other conditions like gastroschisis, kidney abnormalities and placental bleeding. Maternal serum screening now includes hCG and estriol to increase aneuploidy detection, with estriol being added in the mid 1990's. Since that time many screening tests have shown abnormally low levels of estriol (≤0.10 MoM). These low values have been reported in association with anencephaly, Smith-Lemli-Opitz, fetal adrenal hypoplasia, high-dose corticosteroid therapy and steroid sulfatase deficiency. We report on 4 cases of very low estriol levels detected through maternal serum screening and referred to our center. The values were 0.02 MoM, <0.03 MoM, 0.06 MoM and 0.10 MoM. In all cases the mothers were found to be carriers of a microdeletion in the steroid sulfatase (STS) region at Xp22.3 by FISH analysis. All had affected sons. Three were detected by amniocentesis and one was tested after delivery. Three cases had a family history of very dry skin consistent with an X-linked recessive inheritance pattern. STS deficiency should be considered when counseling patients presenting with very low maternal serum estriol levels. STS deficiency or X-linked ichthyosis is characterized by dark scaly skin most prominent on the back, neck, face and extremities. Approximately 25% of affected males may develop mild comeal opacities. Carrier females may have mild symptoms. In an estimated 5% of cases, a more severe phenotype may be present resulting from a larger deletion and leading to a contiguous gene syndrome. Other conditions mapped to Xp22.3 include short statue, chondrodysplasia punctata, mental retardation. Kallmann syndrome and ocular albinism Carrier testing and prenatal diagnosis are available. Testing can help elucidate the reason for low estriol levels and identify women at risk for prolonged labor and failure to dilate due to placental sulfatase deficiency. A detailed family history may assist in determining the risk of STS deficiency or a more severe contiguous gene syndrome.