Prenatal diagnosis of primary microcephaly in two consanguineous families by confrontation of morphometry with DNA data.

Background Prenatal diagnosis of autosomal recessive primary microcephaly (MCPH) is hampered by the fact that fetal head size is normal until late in the pregnancy, and by the vast genetic heterogeneity and impractically large size of the currently known genes for the disorder. Objective Combine DNA and morphometric approaches into earlier prenatal diagnosis of MCPH. Methods We evaluated two consanguineous families affected with MCPH with an ongoing, second-trimester pregnancy. Fetal heads were evaluated by serial ultrasound scannings, and DNA was sampled from parents, probands, and fetal cells, for a focused mutation search and linkage analysis. Results DNA linkage analysis and fetal head morphometry were concordant in one family and probably concordant in the second, showing a healthy fetus and an affected fetus, respectively. Conclusions Cautious confrontation of linkage and morphometric data in selected cases of MCPH from consanguineous families may decrease false-positive and false-negative errors of second-trimester prenatal diagnosis. Copyright (C) 2006 John Wiley & Sons, Ltd.