Clinical, cytogenetic and molecular studies in 65 patients with isolated lissencephaly sequence (ILS) are reported from Indiana University School of Medicine, Indianapolis; Tufts New England Medical Center, Boston; Eastern Virginia Medical School, Norfolk; University of Washington School of Medicine, Seattle; and Baylor College of Medicine, Houston. All patients had type I lissencephaly of varying severity and a grossly normal cerebellum; 17% had agenesis of the corpus callosum and 21% had cavum septi pellucidi. The facial appearance was described as essentially normal, but subtle abnormalities were observed, including microcephaly (71%), bitemporal hollowing (70%), abnormal nasal bridge (49%), and small jaw (58%). All were severely mentally retarded, and 76% had a mixed seizure disorder that progressed to infantile spasms in 35%. Seizures were uncommon during the first few months of life, but opisthotonos was often reported. Hypotonia evolved into spasticity, and feeding difficulties usually improved after several days or weeks. During pregnancy, prolonged or heavy vaginal bleeding occurred in 12% and flu-like syndromes in the mothers of 12%. CP and MRI appearances showed a smooth cerebral surface with open sylvian region, a typical “figure-8” appearance on axial images and enlarged posterior lateral ventricles (colpocephaly). Molecular studies showed microdeletions in chromosome band 17p (6 patients). Other causes included autosomal recessive inheritance, intrauterine infection and intrauterine perfusion failure. The calculated risk of recurrence in sibs was 7%. [1]

COMMENT. For further reports on lissencephaly see Ped Neur Briefs August 1991; 5:59-60; June 1992; 6:48. The role of human fetal ependyma in the pathogenesis of some cerebral malformations such as lissencephaly/pachygyria and holoprosencephaly is reviewed by Dr. Harvey B. Sarnat [2]. Lissencephaly is a primary disturbance of neuroblast migration associated with abnormal gyration of the cerebral cortex. Ependymal abnormalities include persistence of the fetal pseudostratified columnar organization and subventricular rosettes of ependymal cells. The author provides an excellent account of the pathogenesis of cerebral dysgenesis.