Norman–Roberts syndrome: prenatal diagnosis and autopsy findings

Abstract

We report on the autopsy findings of a male fetus in the 27th week of gestation with Norman-Roberts syndrome. The unaffected parents are first cousins and have a five-year-old child with a low, sloping forehead, broad and prominent nasal bridge, widely set eyes, severe psychomotor retardation, and an 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 measurements of the biparietal diameter and head circumference was found. Both the biparietal diameter (57 mm, <5th percentile) and the head circumference (207 mm, <5th percentile) showed a delay of at least two weeks in comparison with other non-cephalic somatometric parameters, that were normal for the gestational age (femur length: 46 mm=median value). After termination of pregnancy, post-mortem examination showed a normotrophic fetus with microcrania and marked microcephaly (brain weight: 50 g), low, sloping forehead, broad and prominent nasal bridge, and widely set eyes. The cerebral hemispheres displayed an almost completely smooth surface with poorly defined sylvian fissures and failure of operculization of the insula. Microscopic examination 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. The syndromes with lissencephaly are reviewed.