Lissencephaly is a brain malformation characterized by absence of gyral for
mation, resulting in a smooth brain surface, Histologic study shows severe
anomalies of cerebral cortical development. Several lissencephaly syndromes
have been described. Here we report a familial syndrome of Lissencephaly,
cleft palate, diffuse agyria, and severe cerebellar hypoplasia. Microscopic
examination of the abnormally thick cerebral cortex showed absence of cort
ical layering, with preservation of the pia-glial barrier. This is the firs
t report of recurrent lissencephaly with cleft palate and severe cerebellar
hypoplasia in which these unique neuropathology findings are described. Au
tosomal recessive inheritance is suggested by recurrence in sibs within the
same family, but germ cell mosaicism for a dominant mutation is not exclud
ed. Am. J. Med. Genet. 87:440-445, 1999. (C) 1999 Wiley-Liss, Inc.