FETAL OCULOCEREBRORENAL SYNDROME OF LOWE ASSOCIATED WITH ELEVATED MATERNAL SERUM AND AMNIOTIC-FLUID ALPHA-FETOPROTEIN LEVELS

Objective: To report an association between fetal oculocerebrorenal sy ndrome of Lowe and elevations in maternal serum alpha-fetoprotein (MSA FP) and amniotic fluid alphafetoprotein (AFAFF). Methods: Case 1 was i dentified during routine MSAFP screening. Cases 2-5 were identified th rough review of a data base of individuals with oculocerebrorenal synd rome enrolled at the National Institutes of Health. To estimate the fr equency of this association, only those whose mothers would have been in the early second trimester from February 1987 to August 1993 were e numerated. The MSAFP was assumed to be normal unless explicitly report ed or unless information outside the data base confirmed that MSAFP wa s not determined. Results: An elevated MSAFP (2.5 multiples of the med ian [MoM] or greater) was detected in five of 20 pregnancies with a fe tus affected by oculocerebrorenal syndrome. Maternal serum alpha-fetop rotein was greater than 5.0 MoM in three pregnancies undergoing amnioc entesis, and all had an elevated AFAFP without significant acetylcholi nesterase activity. No abnormalities were found by ultrasound, and the re was no other cause of elevated AFP identified postnatally. Family h istory was positive in three of the five cases. The mothers were carri ers in four of the five cases, whereas the fifth case appeared to be a spontaneous mutation. Conclusions: Elevated 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 ma y be related to fetal renal tubular dysfunction. A directed interview, focusing on a maternal family history of male relatives with unexplai ned mental retardation, early institutionalization, or congenital rube lla, is appropriate with unexplained MSAFP elevations and, particularl y, with unexplained AFAFF elevations without acetylcholinesterase acti vity.