Clinical and diagnostic features in lissencephaly type 1

The incentive to start this study in 1986 were two patients with lissencephaly, observed during my training as a neurologist. Such an exceptional occasion prompted an attempt to collect a large group of patients with lissencephaly type I, a rare congenital disorder, in order to increase our knowledge about epidemiology, clinical signs, neurophysiological and neuro-imaging characteristics, and genetic aspects. Thanks to the cooperation of many colleagues in departments of childneurology in the Netherlands, it became possible to collect the patients described in this thesis. In Chapter 1 a survey of the present knowledge concerning lissencephaly is given. The differences between lissencephaly type I and type II are explained. This thesis concerns the type I only. Chapter 2 deals about the epidemiology of lissencephaly and is probably the first study about the prevalence at birth and the survival rate of lissencephaly type I. The clinical details of the patients studied are presented in Chapter 3. The diagnostic methods in lissencephaly type I are explored in Chapter 4 (neurophysiology) and in Chapter 5 (neuroimaging). A special type of lissencephaly type I, the Miller-Dieker syndrome, has recently become related to a deletion of the short arm of chromosome 17. In Chapter 6 the details of cytogenetical and DNA-studies are described. Chapter 7 reports three patients with the Smith-Magenis syndrome, which is also characterized by a deletion of a part of the short arm of chromosome 17.