New syndrome? Lissencephaly type III, stippled epiphyses and loose, thick skin: A new recessively inherited syndrome

We report on two new cases of syndromic lissencephaly in two consanguineous sibs, with skeletal abnormality, born to young, healthy, second cousin par ents with healthy children. In Case 1, fetal ultrasound screening at 32 wee ks of gestation showed microcephaly, skin infiltration and equinovarus feet . MRI disclosed cerebral agyria, hypoplastic cerebral mantle and posterior agenesis of the corpus callosum. The propositus, a boy, died soon after bir th at term. In Case 2, fetal ultrasound study performed at 16 weeks of gest ation disclosed skin infiltration. MRI at 22 weeks of gestation showed micr ocephaly with agenesis of corpus callosum and cerebellar hypoplasia. Pregna ncy was terminated at 22 weeks of gestation. The fetus had normal 46, XY ka ryotype and similar anomalies found in the index case, with cranio-facial e dema and arthrogryposis. X-ray films showed epiphyseal stippling of cervica l vertebrae, feet and sacrum. Metacarpal bones were shortened with hypoplas tic distal phalanges. Neuropathological findings were concordant with the p attern described in type III lissencephaly: an agyric brain with hypoplasti c brain stem and cerebellum, severe neuronal loss of the cortical plate, ma trix zone, basal ganglia, brainstem nuclei and spinal cord with axonal swel ling and microcalcification, This entity seems to be a new syndromic lissen cephaly type III, because of epiphyseal calcifications and metacarpophalang eal bone dysplasia. (C) 2001 Wiley-Liss, Inc.