Historical note and nomenclature
Lissencephaly (literally meaning “smooth brain”) is a neuronal migration disorder that includes both agyria and pachygyria but excludes polymicrogyria and other cortical dysplasias. It was first described in 1904 and was considered rare until CT and MRI scans came into widespread use. Most patients have mutations involving LIS1 or XLIS (DCX) genes.
A recognizable "lissencephaly syndrome," later renamed Miller-Dieker syndrome, was described in a series of papers between 1962 and 1980 (Miller 1963; Dieker et al 1969; Jones et al 1980). The association between Miller-Dieker syndrome and visible deletions of chromosome band 17p13.3 was first reported in 1983 (Dobyns et al 1983; Stratton et al 1984), and submicroscopic deletions of the same region were reported in 1988 (vanTuinen et al 1988). Children with classic lissencephaly who lack the facial changes of Miller-Dieker syndrome are classified separately as isolated lissencephaly sequence (Dobyns et al 1984). The association between isolated lissencephaly sequence and smaller submicroscopic deletions in chromosome 17p13.3 was first described in 1992 (Ledbetter et al 1992).
Above: Neurology Medlink. Publication dates Originally released October 31, 1994; last updated June 18, 2012; expires June 18, 2015
Pachygyria is a rare developmental disorder which results from abnormal migration of neurons in the developing brain and nervous system.[1] In pachygyria, the gyri are relatively few and are unusually broad and flat. The condition does not affect the entire brain, and is also known as ‘incomplete lissencephaly.’[2] Symptoms are variable, but may include seizures, developmental
delay, growth failure, small head size, feeding issues and poor muscle control.[1] Most cases are isolated, although autosomal dominant and recessive forms have been described.[1][3] Treatment is symptomatic and supportive.[1][2]
Reference: National Institutes of Health
Some forms of lissencephaly and pachygyria have been identified and are more common than others. Even those without a formal name have a ranking in the genetic line-up.
Classical lissencephaly, also known as type I or generalized agyria-pachygyria, is a severe brain malformation of a smooth cerebral surface, abnormally thick (10-20mm) cortex with four layers, widespread neuronal heterotopia, enlarged ventricles, and agenesis or malformation of the corpus callosum.[6][7] Classical lissencephaly can range from agyria to regional pachygyria and is usually present along with subcortical band heterotopia (known as ‘double cortex’ to describe the
circumferential bands of heterotopic neurons located beneath the cortex).[7] Subcortical band heterotopia is a malformation slightly different from lissencephaly that is now classified under the agyria-pachygyria-band spectrum because it consists of a gyral pattern consistent with broad convolutions and an increased cortical thickness.[1] The established classification scheme for lissencephaly is based on the severity (grades 1-6) and the gradient.[5]
- Grade 1: generalized agyria
- Grade 2: variable degree of agyria
- Grade 3: variable degree of pachygyria
- Grade 4: generalized pachygyria
- Grade 5: mixed pachygyria and subcortical band heterotopia
- Grade 6: subcortical band heterotopia alone
- Gradient ‘a’: from posterior to anterior gradient
- Gradient ‘b’: from anterior to posterior gradient [5]
Grade 1 and Grade 4 are very rare. Grade 2 is observed in children with Miller-Dieker syndrome (a combination of lissencephaly with dysmorphic facial features, visceral abnormalities, and polydactyly). The most common lissencephaly observed, consisting of frontotemporal pachygyria and posterior agyria, is Grade 3.[6] Another malformation worth mentioning because of its connections to pachygyria is polymicrogyria. Polymicrogyria is characterized by many small gyri separated by shallow sulci, slightly thin cortex, neuronal heterotopia and enlarged ventricle and is often superimposed on pachygyria.[6]
Reference: Wikipedia
As unique and confusing as the various disorders can be, you can see that many share a common thread. This is why genetic testing is seriously needed in this field. Only when we begin to define these disorders can we find the cure.
