Mutations in the ARFGEF2 gene must be considered in the presence of bilateral periventricular nodular heterotopia and putaminal hyperintensity in children presenting with movement disorder, severe developmental delay and microcephaly.
The presence of periventricular heterotopia, acquired microcephaly and suspected recessive inheritance led to mutation analysis of ARFGEF2 in two affected siblings and their healthy consanguineous parents, after mutations in FLNA had been ruled out.
Loss of ARFGEF2 function affects vesicle trafficking, proliferation/apoptosis, and neurotransmitter receptor function.This can explain BPNH and microcephaly.
A rare, recessive form of bilateral PNH with microcephaly and severe delay is associated with mutations of the ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2) gene, required for vesicle and membrane trafficking from the trans-Golgi.