Norman-Roberts syndrome: prenatal diagnosis and autopsy findings

We report on the autopsy findings of a male fetus in the 27th week of gesta tion with Norman-Roberts syndrome. The unaffected parents are first cousins and have a five-year-old child with a low, sloping forehead, broad and pro minent nasal bridge, widely set eyes, severe psychomotor retardation, and a n agyric cortex. Prenatal diagnosis showed a small head at the 25th week of gestation. At this time, a slowing-down of the growth of the sonographic m easurements of the biparietal diameter and head circumference was found. Bo th the biparietal diameter (57 mm, <5th percentile) and the head circumfere nce (207 mm, <5th percentile) showed a delay of at least two weeks in compa rison with other non-cephalic somatometric parameters, that were normal for the gestational age (femur length: 46 mm = median value). After terminatio n of pregnancy, post-mortem examination showed a normotrophic fetus with mi crocrania and marked microcephaly (brain weight: 50 g), low, sloping forehe ad, broad and prominent nasal bridge, and widely set eyes. The cerebral hem ispheres displayed an almost completely smooth surface with poorly defined sylvian fissures and failure of operculization of the insula. Microscopic e xamination showed a predominantly four-layered cortex (lissencephaly type I ). Karyotype was normal and in situ hybridization did not show any deletion in the Miller-Dieker/isolated lissencephaly critical region on 17p13.3. Th e syndromes with lissencephaly are reviewed. Copyright (C) 2000 John Wiley & Sons, Ltd.