Periventricular nodular heterotopia is commonly associated with a mutation in which gene?

Periventricular nodular heterotopia is commonly associated with a mutation in which gene?

• A. LIS1
• B. FLNA
• C. DCX
• D. SHH

Answer: (B)

Periventricular nodular heterotopia happens when neurons fail to migrate from the ventricular zone to the cortex and instead form nodules along the ventricles. A classic genetic cause is mutations in FLNA, which encodes filamin A, a protein that cross-links actin and helps anchor cells to the cytoskeleton during migration. When FLNA is defective, the cytoskeletal changes needed for neurons to move outward are disrupted, so neurons arrest near the ventricles and create those nodules. This condition is typically X-linked dominant, so it often presents in females, with affected males usually having more severe outcomes or limited survival, though mosaic cases can occur. Other genes you might hear about—LIS1 and DCX—are more commonly linked to lissencephaly or subcortical band heterotopia rather than the classic periventricular nodular pattern. SHH is involved in midline brain development, not this migration defect.

Periventricular nodular heterotopia happens when neurons fail to migrate from the ventricular zone to the cortex and instead form nodules along the ventricles. A classic genetic cause is mutations in FLNA, which encodes filamin A, a protein that cross-links actin and helps anchor cells to the cytoskeleton during migration. When FLNA is defective, the cytoskeletal changes needed for neurons to move outward are disrupted, so neurons arrest near the ventricles and create those nodules.

This condition is typically X-linked dominant, so it often presents in females, with affected males usually having more severe outcomes or limited survival, though mosaic cases can occur.

Other genes you might hear about—LIS1 and DCX—are more commonly linked to lissencephaly or subcortical band heterotopia rather than the classic periventricular nodular pattern. SHH is involved in midline brain development, not this migration defect.