Bilateral Frontoparietal Polymicrogyria - DIAGNOSIS

DIAGNOSIS

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 bilateral frontoparietal polymicrogyria 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 apart 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 bilateral 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.