Diagnostic criteria for a BFPP patient entails a heterozygous genotype for a deletion of chromosome 16q12.1-q21 region, including GPR56 gene. To date the only gene known to be associated with polymicrogyria is GPR56. Testing for GPR56-related<unk>  is available clinically. Mutations in GPR56 hinders Collagen III, its specific ligand, to bind in a developing brain. To date, a total of fourteen BFPP-associated mutations have been identified, including one deletion, two splicing, and eleven missense mutations. Two mutations in the GPCR proteolytic site (GPS) domain, C346S and W349S, cause a brain malformation through trapping the mutated proteins in the endoplasmic reticulum. GPR56 are a part of the B class of the GPCR family, the largest cell surface gene family in the human genome. Within this family there are different types of bio-active molecules that transduce their signal to the intracellular compartment via interaction with this type of receptor. Children often present with developmental delay, spasticity, or seizures; they are also often microcephalic. Some patients with polymicrogyria go undiagnosed until they produce children with the disorder who have more severe manifestations. Retrospectively, these patients will often report some difficulty in their medical or educational history. BFPP patients demonstrate mental retardation, language impairment, motor developmental delay, and seizure disorders such as epilepsy. The association of epilepsy is in approximately 50% to 85% of affected BFPP patients. The clinical manifestations of polymicrogyria are stable neurologic deficits: In the mildest form, polymicrogyria is unilateral with only one small region of the brain involved; neurologic problems may not be evident. In more severe forms, focal motor, sensory, visual, or cognitive problems may be present, depending on the location of the brain region affected. In the most severe forms, polymicrogyria is<unk>  and generalized, resulting in severe intellectual disability, cerebral palsy, and refractory epilepsy. Individuals with the milder forms of polymicrogyria survive into adulthood, while those with the most severe forms, such as BFPP, may die at a young age as a result of such complications as seizures or pneumonia. The prevalence of isolated polymicrogyria is unknown. Researchers believe that it may be relatively common overall, although BFPP is probably rare. *Radiological findings (MRI) demonstrated symmetric generalized polymicrogyria with decreasing anterior-posterior gradient, most prominent in<unk>  cortex. *Numerous gyrus on the cortex *Small gyri and sulci *Thin cortex Methods/tests This child presented with seizures. The coronal true inversion recovery sequence shows thickened and disordered cortex in superior frontal and cingulate gyri<unk> ly (arrow). There are small convolutions visible at the corticomedullary junction. The appearance is that of cortical dysplasia, with polymicrogyria more likely than pachygyria due to the small convolutions visible. There are also small foci of grey matter signal in the corpus callosum, deep to the dysplastic cortex (double arrows). These probably represent areas of grey matter heterotopia. There are different tests or methods used to determine GPR56 expression or visuals of the brain to analyze the specific sections that are affected. These tests for example, using animals such as mice, RNAi, Behavioral assay, Electron microscopy, CT scan, or MRI demonstrate different results that concludes an affected BFPP patient. MRI's reveal either irregularity to the cortical surface suggestive of multiple small folds or an irregular, scalloped appearance of the gray matter-white matter junction. Neuroimaging The diagnosis of polymicrogyria is typically made by magnetic resonance imaging (MRI) since computed tomography (CT) and other imaging methods generally do not have high enough resolution or adequate contrast to identify the small folds that define the condition. The cerebral cortex often appears abnormally thick as well because the multiple small gyri are fused, infolded, and superimposed in appearance. Neuropathology Gross neuropathologic examination reveals a pattern of complex convolutions to the cerebral cortex, with miniature gyri fused and superimposed together, often resulting in an irregular brain surface. The cortical ribbon can appear excessively thick as a result of the infolding and fusion of multiple small gyri. Microscopic examination demonstrates that the cerebral cortex is in fact abnormally thin and has abnormal lamination; typically the cortex is unlayered or has four layers, in contrast to the normal six layers. The most superficial layers between adjacent small gyri appear fused, with the pia (layer of the meninges) bridging across multiple gyri. Prenatal diagnosis for BFPP is also available for pregnancies at risk if the GPR56 mutations have been identified in an affected family member.
Bilateral frontoparietal polymicrogyria
Hippocampal sclerosis
Posterior cortical atrophy
Polymicrogyria
Periodic lateralized epileptiform discharges
Gray matter heterotopia
Agenesis of the corpus callosum
Olivopontocerebellar atrophy