Parents of a proband

- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.

- Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

- At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

- Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3.

- Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

- Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele.

- In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.

Other family members of a proband.

- Each sibling of the proband's parents is at a 50% risk of being a carrier

Bilateral frontoparietal polymicrogyria (BFPP) is a genetic disorder with autosomal recessive inheritance that causes a cortical malformation. Our brain has folds in the cortex to increase surface area called gyri and patients with polymicrogyri have an increase number of folds and smaller folds than usual. Polymicrogyria is defined as a cerebral malformation of cortical development in which the normal gyral pattern of the surface of the brain is replaced by an excessive number of small, fused gyri separated by shallow sulci and abnormal cortical lamination. From ongoing research, mutation in GPR56, a member of the adhesion G protein-coupled receptor (GPCR) family, results in BFPP. These mutations are located in different regions of the protein without any evidence of a relationship between the position of the mutation and phenotypic severity. It is also found that GPR56 plays a role in cortical pattering.

The cause of polymicrogyria is unclear. It is currently classified as resulting from abnormalities during late neuronal migration or early cortical organization of fetal development. Evidence for both genetic and non-genetic causes exists. Polymicrogyria appears to occur around the time of neuronal migration or early cortical development. Non-genetic causes include defects in placental oxygenation and in association with congenital infections, particularly cytomegalovirus.

An association with the gene WDR62 has been identified.

Polymicrogyria is a disorder of neuronal migration, resulting in structurally abnormal cerebral hemispheres. The Greek roots of the name describe its salient feature: many [poly] small [micro] gyri (convolutions in the surface of the brain). It is also characterized by shallow sulci, a slightly thicker cortex, neuronal heterotopia and enlarged ventricles. When many of these small folds are packed tightly together, PMG may resemble pachygyria (a few "thick folds" - a mild form of lissencephaly).

The pathogenesis of polymicrogyria is still being researched for understanding though it is historically heterogeneous-4. It results from both genetic and destructive events. While polymicrogyria is associated with genetic mutations, none of these are the sole cause of this abnormality. The cortical development of mammals requires specific cell functions that all involve microtubules, whether it is because of mitosis, specifically cell division, cell migration or neurite growth. Some mutations that affect the role of microtubules and are studied as possible contributors, but not causes, to polymicrogyria include TUBA1A and TUBB2B. TUBB2B mutations are known to contribute to polymicrogyria either with or without congenital fibrosis or the external ocular muscles, as well as bilateral perisylvian.

The gene GPR56 is a member of the adhesion G protein-coupled receptor family and is directly related to causing Bilateral frontoparietal polymicrogyria, (BFPP)-6. Other genes in the G protein-coupled receptor family have effects with this condition as well such as the outer brain development, but not enough is known to carry out all the research properly so the main focus is starting with the specific GR56 gene within this category. This malformation of the brain is a result of numerous small gyri taking over the surface of the brain that should otherwise be normally convoluted. This gene is currently under studies to help identify and contribute to the knowledge about this condition. It is studied to provide information on the causes along with insight into the mechanisms of normal cortical development and the regional patterning of the cerebral cortex using magnetic resonance imagine, MRI. Specifically found to polymicrogyria due to mutation of this gene are myelination defects. GPR56 is observed to be important for myelinations due to a mutation in this gene results in reduced white matter volume and signal changes as shown in MRI’s. While the cellular roles of GPR56 in myelination remains unclear, this information will be used to further other studies done with this gene.