Movement disorder and neuronal migration disorder due to ARFGEF2 mutation.
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.
de Wit
M C Y
MC
Department of Pediatric Neurology, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
de Coo
I F M
IF
Halley
D J J
DJ
Lequin
M H
MH
Mancini
G M S
GM
D000015:Abnormalities, Multiple / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D054091:Periventricular Nodular Heterotopia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype
C119088:ARFGEF2 protein, human; D020662:Guanine Nucleotide Exchange Factors