Outcome analysis of pregnancies screening positive for Smith-Lemli-Optiz syndrome. M. Steinraths1, A. Mattman2, S. Langlois1,2. 1) Dept of Medical Genetics; 2) Dept of Pathology, University of British Columbia, Vancouver, BC, Canada.
Smith-Lemli-Opitz syndrome (SLOS) is characterized by growth retardation, developmental delay, and minor/major malformations. Due to low fetal cholesterol, SLOS presents with low maternal serum unconjugated estriol (uE3). Other conditions presenting with low uE3 on triple marker screen (TMS) include trisomy 18, triploidy, anencephaly, steroid sulfatase (STS) deficiency, fetal adrenal abnormalities and intrauterine fetal demise (IUFD). Our study aims to define the risk for an abnormal outcome in pregnancies screening positive for SLOS when all known causes have been excluded. We applied a SLOS screening algorithm to 100,000 TMS collected between 1995-2005, identifying 260 as screen-positive. Outcome information was obtained for screen-positive pregnancies through chart review and physician questionnaires. To date, outcome is known for 204/260 (78%) pregnancies. Outcomes include IUFD in 87/204 (43%), aneuploidy or triploidy in 45/204 (22%), anencephaly in 12/204 (6%), STS deficiency in 11/204 (5%) and adrenal hypoplasia in 1/204 (0.4%). Maternal steroid treatment was noted in 3/204 (1%). There have been no pregnancies with SLOS identified to date. 45/204 (22%) pregnancies had no recognized cause of low uE3. Outcomes were obtained for these (group 1) and 69 age-matched control pregnancies with normal uE3 (group 2). In group 1, pregnancy and long-term outcome was normal in 25/45 (56%). Intrauterine growth restriction (IUGR) was seen in 6/45 (13%) and pregnancy-induced hypertension (PIH) in 4/45 (9%). Multiple congenital anomalies were present in 10/45 (22%). In group 2, outcome was normal in 63/69 (91%), IUGR was seen in 1/69 (1%) and PIH in 3/69 (4%). Developmental delay and congenital anomalies were seen in 2/69 (3%). Proposed etiologies for an increased rate of abnormal outcome in pregnancies with low uE3 on TMS include multiple congenital anomaly syndromes affecting the pituitary/adrenal axis or cholesterol biosynthesis disorders other than SLOS. This outcome information will allow comprehensive genetic counseling of pregnancies screening positive for SLOS and improve assessment of newborns with low uE3 identified prenatally.