This annotation describes the clinical and pathological features of several conditions believed to result from a primary defect in cell migration which include the
lissencephalies, pachygria,
polymicrogyrias, and
focal cortical dysplasia. A variety of factors must be considered in pathogeneses, including cellular proliferation, cell death, post-migrational intracortical growth and development, axonogenesis and dendritogenesis. At least two distinct types of
lissencephaly exist. Classic (also known as Type I)
lissencephaly is the prototypic pattern being seen in autosomal dominant
Miller-Dieker syndrome, in addition to autosomal recessive and X-linked forms. The
Miller-Dieker syndrome locus (LIS-1) encodes the
platelet activating factor acetylhydrolase-1, beta1 subunit. The gene for an X-linked form of
lissencephaly (XLIS) encodes a
protein called doublecortin. Cobblestone (type II)
lissencephaly is most commonly seen in patients with the
Walker-Warburg syndrome, and also occurs in a group of disorders associated with congenital
muscular dystrophy, including Finnish '
muscle-eye-brain' disease and
Fukuyama muscular dystrophy. Controversy exits as to whether
polymicrogyria is a malformation or a disruption of development. The answer is likely both.
Polymicrogyria is believed to arise from defects occurring between 17 and 25 or 26 weeks gestation. Heterotopia can be sporadic, inherited as a simple Mendelian trait, or may be part of a more complex syndrome being characterized by collections of disorganized grey matter in inappropriate places.
X-linked periventricular heterotopia syndrome is caused by mutations in filamin-1. In addition to those described above, many other syndromes show
lissencephaly,
pachygyria and
polymicrogyria and many cases are not easily classified into any particular syndrome.