We report a child with a severe choreadystonic movement disorder, bilateral periventricular nodular heterotopia (BPNH), and secondary microcephaly based on compound heterozygosity for two new ARFGEF2 mutations (c.2031_2038dup and c.3798_3802del), changing the limited knowledge about the phenotype. The brain MRI shows bilateral hyperintensity of the putamen, BPNH, and generalized atrophy. Loss of ARFGEF2 function affects vesicle trafficking, proliferation/apoptosis, and neurotransmitter receptor function. This can explain BPNH and microcephaly. We hypothesize that the movement disorder and the preferential damage to the basal ganglia, specifically to the putamen, may be caused by an increased sensitivity to degeneration, a dynamic dysfunction due to neurotransmitter receptor mislocalization or a combination of both.

Additional Metadata
Keywords ARFGEF2, BIG2, Basal ganglia, Bilateral periventricular nodular heterotopia, Child, Extrapyramidal movement disorder, FLNA, Microcephaly
Persistent URL dx.doi.org/10.1007/s10048-009-0192-2, hdl.handle.net/1765/26954
Journal Neurogenetics
de Wit, M.C.Y, de Coo, I.F.M, Halley, D, Leguin, M, & Mancini, G.M.S. (2009). Movement disorder and neuronal migration disorder due to ARFGEF2 mutation. Neurogenetics, 10(4), 333–336. doi:10.1007/s10048-009-0192-2