Major fetal abnormalities associated with positive screening tests for Smith-Lemli-Opitz syndrome (SLOS).
OBJECTIVE
Determine the relationship between positive screening interpretations for Smith-Lemli-Opitz syndrome (SLOS) and other fetal abnormalities, to aid counseling and diagnostic activities.


METHODS
An SLOS screening algorithm was incorporated into California's second-trimester screening program for Down syndrome and open neural tube defects (ONTDs). Between 2002 and 2004, 777 088 pregnant women were given an SLOS risk interpretation, using alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG) measurements. Outcomes were obtained in 98.8% of screen-positive pregnancies.


RESULTS
SLOS screen positives, alone or in combination with screen positives for other fetal disorders (Down syndrome, trisomy 18, ONTD), were associated with a high risk for fetal pathology. Type and frequency of chromosomal or anatomic abnormalities (or fetal death) varied according to screen-positive combination. Among 2018 screen-positive pregnancies, 644 fetal deaths were identified. Among the 1374 viable pregnancies, 519 were screen positive for SLOS alone; two SLOS cases and 51 other serious abnormalities were identified (14 aneuploidies; 37 anatomic). The remaining 855 were also screen positive for at least one other disorder; two SLOS cases and 327 other abnormalities were identified (180 aneuploidies; 157 anatomic).


CONCLUSIONS
For screening programs implementing the SLOS algorithm, the present data may be useful for counseling and to guide diagnostic studies.
Craig
Wendy Y
WY
Foundation for Blood Research, Scarborough, ME, UK.
Haddow
James E
JE
Palomaki
Glenn E
GE
Roberson
Marie
M
D000328:Adult; D002140:California / Q000453:epidemiology; D006063:Chorionic Gonadotropin / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D004964:Estriol / Q000097:blood; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009436:Neural Tube Defects / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology* / Q000517:prevention & control; D000509:alpha-Fetoproteins
D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D004964:Estriol