Fetal Oculocerebrorenal Syndrome of Lowe Associated With Elevated Maternal Serum and Amniotic Fluid Alpha-Fetoprotein Levels

OBJECTIVETo report an association between fetal oculocerebrorenal syndrome of Lowe and elevations in maternal serum alpha-fetoprotein (MSAFP) and amniotic fluid alphafetoprotein (AFAFP). METHODSCase 1 was identified during routine MSAFP screening. Cases 2–5 were identified through review of a data base of individuals with oculocerebrarenal syndrome enrolled at the National Institutes of Health. To estimate the frequency of this association, only those whose mothers would have been in the early second trimester from February 1987 to August 1993 were enumerated. The MSAFP was assumed to be normal unless explicitly reported or unless information outside the data base confirmed that MSAFP was not determined. RESULTSAn elevated MSAFP (2.5 multiples of the median [MoM] or greater) was detected in five of 20 pregnancies with a fetus affected by oculocerebrorenal syndrome. Maternal serum alpha-fetoprotein was greater than 5.0 MoM in three pregnancies undergoing amniocentesis, and all had an elevated AFAFP without significant acetylcholinesterase activity. No abnormalities were found by ultrasound, and there was no other cause of elevated AFP identified postnatally. Family history was positive in three of the five cases. The mothers were carriers in four of the five cases, whereas the fifth case appeared to be a spontaneous mutation. CONCLUSIONSElevated MSAFP and AFAFP appear to occur at a higher than expected frequency in pregnancies carrying an oculocerebrorenal syndrome fetus. The mechanism of elevation of AFP may be related to fetal renal tubular dysfunction. A directed interview, focusing on a maternal family history of male relatives with unexplained mental retardation, early institutionalization, or congenital rubella, is appropriate with unexplained MSAFP elevations and, particularly, with unexplained AFAFP elevations without acetylcholinesterase activity.