Prenatal Diagnosis of Lissencephaly Type 2 using Three-dimensional Ultrasound and Fetal MRI: Case Report and Review of the Literature

Abstract

Lissencephaly is a genetic heterogeneous autosomal recessive disorder characterized by the classical triad: brain malformations, eye anomalies, and congenital muscular dystrophy. Prenatal diagnosis is feasible by demonstrating abnormal development of sulci and gyri. Magnetic resonance imaging (MRI) may enhance detection of developmental cortical disorders as well as ocular anomalies. We describe a case of early diagnosis of lissencephaly type 2 detected at the time of routine second trimester scan by three-dimensional ultrasound and fetal MRI. Gross pathology confirmed the accuracy of the prenatal diagnosis while histology showed the typical feature of cobblestone cortex. As the disease is associated with poor perinatal prognosis, early and accurate prenatal diagnosis is important for genetic counseling and antenatal care.

Fig. 1

Transabdominal three-dimensional ultrasound in rendering mode performed at 21 weeks and 5 days of gestation. Navigation within the volume detected severe communicating hydrocephalus. Abnormal posterior fossa with cerebellar hypoplasia was also detected, as well as a thin mantel of cortex. No parieto-occipital fissure or calcarine sulcus could be observed.

Fig. 2

(A) T2-weighted fetal magnetic resonance imaging confirmed in coronal section the findings of communicating hydrocephalus (double arrow), cerebellar hypoplasia (c) and pachygyria (*); (B) T2-weighted image in sagittal plane showed brainstem hypoplasia with typical “Z”-shaped morphology (black arrow) and dilated fourth ventricle. The mantel of the cerebral cortex was characterized by pachygyria (asterisk). A diagnosis of lissencephaly was elicited.

Fig. 3

(A) Histology shows the typical cobblestone pattern of the cerebral cortex in lissencephaly type 2. Cortical layers are absent and there is an irregular scramble of neurons mixed with underlying white matter. (B) Histology shows normal fetal cortex at 22 weeks of gestation. The primitive neurons, migrating from the germinal matrix, are orderly piled up. No definite layers are recognizable yet.

Fig. 4

Macroscopy of fetal brain shows a coronal section through the midline. The cortical surface is smooth (agyria). The normal gray-white matter distribution is not recognizable, but there is evidence of a discontinuous subcortical gray line (arrow). Lateral ventricles are enlarged and hippocampi are upright.