Bilateral Frontoparietal Polymicrogyria - DIAGNOSIS - Associated Conditions

Associated Conditions

BFPP is a cobblestone-like cortical malformation of the brain. Disruptions of cerebral cortical development due to abnormal neuronal migration and positioning usually lead to cortical disorders, which includes cobblestone lissencephaly. Cobblestone lissencephaly is typically seen in three different human congenital muscular dystrophy syndromes: Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease. In cobblestone lissencephaly, the brain surface actually has a bumpy contour caused by the presence of collections of misplaced neurons and glial cells that have migrated beyond the normal surface boundaries of the brain. Sometimes regions populated by these misplaced cells have caused a radiologic misdiagnosis of polymicrogyria. However, the presence of other abnormalities in these cobblestone lissencephaly syndromes, including ocular anomalies, congenital muscular dystrophy, ventriculomegaly, and cerebellar dysplasia, usually distinguishes these disorders from polymicrogyria.There are no anatomopathologic studies that have characterized the pattern of cortical laminar alterations in patients with GPR56 gene mutations, but it has been suggested that the imaging characteristics of BFPP, including myelination defects and cerebellar cortical dysplasia, are reminiscent of those of the so-called cobblestone malformations (muscle-eye-brain disease and Fukuyama congenital muscular dystrophy) that are also associated with N-glycosylation defects in the developing brain.

Lissencephaly ("smooth brain") is the extreme form of pachygyria. In lissencephaly, few or no sulci are seen on the cortical surface, resulting in a broad, smooth appearance to the entire brain. Lissencephaly can be radiologically confused with polymicrogyria, particularly with low-resolution imaging, but the smoothness and lack of irregularity in the gray-white junction, along with markedly increased cortical thickness, distinguishes lissencephaly.

GPR56 mutation also can cause a severe encelphalopathy which is associated with electro clinical features of the Lennox-Gastaut syndrome. Lennox-Gastaut syndrome can be cryptogenic or symptomatic, but the symptomatic forms have been associated with multiple etiologies and abnormal cortical development. BFPP caused by GPR56 mutations is a representation of a malformation of cortical development that causes Lennox-Gastaut Syndrome.

Polymicrogyria usually gets misdiagnose with pacygyria so therefore it needs to be distinguished from pachygyria. Pachygyria is a distinct brain malformation in which the surface folds are excessively broad and sparse. Pachygyria and polymicrogyria may look similar on low-resolution neuroimaging such as CT because the cortical thickness can appear to be increased and the gyri can appear to be broad and smooth in both conditions. This is why higher resolution neuroimaging are needed such as an MRI.