Lissencephaly type II
Citation, DOI & article data
Lissencephaly type II is characterized by reduction in normal sulcation, associated with a bumpy or pebbly cortical surface (thus the term cobblestone lissencephaly), absent in lissencephaly type I. Unlike type I lissencephaly which is the result of neuronal undermigration, type II is due to overmigration. For a general discussion refer to the article lissencephaly.
Lissencephaly type II is a heterogeneous group of disorders, characterized by a similar morphological change to the brain and congenital muscular dystrophy. The three most commonly included diseases / syndromes are:
- Walker-Warburg syndrome
- Fukuyama congenital muscular dystrophy (FCMD): predominantly reported in Japanese populations 2
- muscle-eye-brain (MEB) disease: predominantly reported in Finnish populations 2
Presentation will vary from patient to patient and particularly depending on the underlying syndrome. In general all have components of developmental delay, hypotonia and ocular abnormalities.
Walker-Warburg syndrome patients are most severely affected with profound hypotonia, severe ocular abnormalities, and neurological impairment. Fukuyama syndrome is intermediate in severity, and muscle-eye-brain disease is least severe with patients exhibiting only mild hypotonia, mild ocular anomalies, and developmental delay 5.
Although a number of different genetic abnormalities have been identified resulting in type II lissencephaly, they share a common feature, namely that neurons fail to normally stop migrating outwards. The underlying abnormality is within the glia limitans, the outermost layer of glial tissue formed by apposed astrocytes and astrocytic foot processes from deeper astrocytes, covered by a basal lamina composed of extracellular matrix, which itself lies in contact with the pia mater 1,3.
In patients with type II lissencephaly alpha-dystroglycan, a highly glycosylated, extracellular peripheral-membrane protein crucial for the formation and stabilization of the glia limitans, is abnormally glycosylated and results in gaps within the glia limitans, allowing the passage of neurons through the glia limitans and into the subarachnoid space 1,3,4.
Each of the related syndromes occur as a result of one or more defects in gene products involved in the normal formation and function of the glia limitans.
Regardless of the exact underlying genetic abnormalities, type II lissencephaly patients share similar gross brain imaging features, best appreciated on MRI.
As the term 'cobblestone lissencephaly' suggests the primary imaging features are:
- lack of normal sulcation
- multinodular surface to the cortex (cobblestone), most pronounced anteriorly
There are numerous other features, seen with variable frequency in the three underlying syndromes. These are discussed in more detail in the respective articles Walker-Warburg syndrome, Fukuyama syndrome and muscle-eye-brain (MEB) disease. In general additional features encountered include 5:
- hypomyelination of white matter
- posterior cephalocele
- abnormal brainstem
- fused colliculi
- small pons
- dysmorphic mesencephalon
- dorsal pontomedullary kink
- abnormal cerebellum
- vermian hypogenesis
- cerebellar hypoplasia
- cerebellar polymicrogyria
- abnormal globes
- uni- or bilateral microphthalmia
- retinal dysplasia
- 1. Volpe JJ. Neurology of the newborn. W B Saunders Co. (2008) ISBN:1416039953. Read it at Google Books - Find it at Amazon
- 2. Pilz DT, Quarrell OW. Syndromes with lissencephaly. J. Med. Genet. 1996;33 (4): 319-23. J. Med. Genet. (link) - Free text at pubmed - Pubmed citation
- 3. Steward O. Principles of cellular, molecular, and developmental neuroscience. Springer. (1989) ISBN:0387968032. Read it at Google Books - Find it at Amazon
- 4. Fumiaki Saito, Kiichiro Matsumura. Skeletal Muscle. doi:10.1186/2044-5040-1-22
- 5. Abdel razek AA, Kandell AY, Elsorogy LG et-al. Disorders of cortical formation: MR imaging features. AJNR Am J Neuroradiol. 2009;30 (1): 4-11. doi:10.3174/ajnr.A1223 - Pubmed citation