Which gene is commonly implicated in periventricular heterotopia?

Which gene is commonly implicated in periventricular heterotopia?

• A. PAX6
• B. CNTNAP2
• C. FLNA
• D. SHANK3

Answer: (C)

Periventricular heterotopia results from a failure of neurons to migrate away from the ventricular zone during brain development. The best-supported gene linked to this condition is FLNA, which encodes filamin A, a cytoskeletal crosslinker that anchors migrating neurons to the radial glial scaffold and coordinates their movement with the cell’s shape changes and signaling. When FLNA is mutated, migrating neurons can’t properly detach and move to the cortical plate, so they arrest along the ventricles and form nodules—periventricular nodular heterotopia. This condition is classically X-linked dominant, reflecting its genetic pattern and, in many cases, its more prominent effect in females. Other genes listed are involved in brain development or synaptic function but are not the typical culprits for this migration defect. PAX6 is a transcription factor important for brain patterning, CNTNAP2 is linked to neuron–glia adhesion and language development, and SHANK3 is a postsynaptic scaffold protein; none of these are the classic driver of the migrational anomaly seen in PVNH.

Periventricular heterotopia results from a failure of neurons to migrate away from the ventricular zone during brain development. The best-supported gene linked to this condition is FLNA, which encodes filamin A, a cytoskeletal crosslinker that anchors migrating neurons to the radial glial scaffold and coordinates their movement with the cell’s shape changes and signaling. When FLNA is mutated, migrating neurons can’t properly detach and move to the cortical plate, so they arrest along the ventricles and form nodules—periventricular nodular heterotopia. This condition is classically X-linked dominant, reflecting its genetic pattern and, in many cases, its more prominent effect in females.

Other genes listed are involved in brain development or synaptic function but are not the typical culprits for this migration defect. PAX6 is a transcription factor important for brain patterning, CNTNAP2 is linked to neuron–glia adhesion and language development, and SHANK3 is a postsynaptic scaffold protein; none of these are the classic driver of the migrational anomaly seen in PVNH.