Bilateral frontoparietal polymicrogyria
Genetic disorder causing excessive small brain folds from GPR56 mutations.
Bilateral frontoparietal polymicrogyria (BFPP) is a genetic disorder with autosomal recessive inheritance that causes a cortical malformation of the brain. It is characterized by an excessive number of small, fused gyri separated by shallow sulci and abnormal cortical lamination, most prominent in the frontoparietal cortex. The disorder results from mutations in the GPR56 gene, a member of the adhesion G protein-coupled receptor family, which plays a role in cortical patterning.
- field
- Medical genetics, neurology
- known_for
- Cortical malformation with polymicrogyria, associated with GPR56 mutations
- inheritance
- Autosomal recessive
- symptoms
- Developmental delay, intellectual disability, seizures, exaggerated reflexes
- associated_conditions
- Cobblestone-like malformation, Lennox-Gastaut syndrome
Lore & Background
Bilateral frontoparietal polymicrogyria is defined as a cerebral malformation of cortical development in which the normal gyral pattern is replaced by an excessive number of small, fused gyri. The disorder is caused by mutations in the GPR56 gene, which encodes a member of the adhesion G protein-coupled receptor family. 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. To date, fourteen BFPP-associated mutations have been identified, including one deletion, two splicing, and eleven missense mutations.
Reader's Guide
BFPP is significant as a rare but illustrative example of how genetic mutations in adhesion GPCRs can disrupt brain development, leading to cortical malformations and severe neurological deficits. The disorder highlights the importance of GPR56 in cortical patterning and neuronal migration. Its clinical manifestations include developmental delay, intellectual disability, seizures, and spasticity, with epilepsy occurring in 50% to 85% of affected patients. Radiologically, BFPP shows symmetric generalized polymicrogyria with a decreasing anterior-posterior gradient, most prominent in the frontoparietal cortex. The condition can be confused with pachygyria or cobblestone lissencephaly on low-resolution imaging, necessitating MRI for accurate diagnosis. Understanding BFPP has implications for diagnosing and distinguishing similar cortical malformations, and for exploring the role of GPCRs in brain development and disease.
Did You Know?
- BFPP is caused by mutations in the GPR56 gene, a member of the adhesion G protein-coupled receptor family.
- The disorder results in an excessive number of small, fused gyri separated by shallow sulci in the brain.
- BFPP can be radiologically confused with pachygyria or cobblestone lissencephaly, especially on low-resolution imaging.
- Mutations in the GPS domain of GPR56, such as C346S and W349S, cause brain malformation by trapping mutated proteins in the endoplasmic reticulum.
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