The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder

Mutations in ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) gene was recently recognized to cause bilateral periventricular nodular heterotopia, putaminal hyperintensity and movement disorder.A ten year-old girl with severe developmental and growth delay, feeding problems and involuntary movements is presented. Bilateral periventricular nodular heterotopia and putaminal hyperintensity were detected in cranial magnetic resonance imaging. Her echocardiographic examination revealed left ventricular non-compaction cardiomyopathy. Sequence analysis of ARFGEF2 gene demonstrated a homozygous c.5126G>A, p.Trp1709^* mutation. The mutation is the first nonsense mutation described in ARFGEF2 gene and the case is the second reported case of ARFGEF2 gene mutation with cardiomyopathy. The presented case supports the view that the presence of cardiomyopathy in ARFGEF2 gene mutations is more than a coincidence and thus expands the phenotypic spectrum of ARFGEF2 gene mutations.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. In case of ARFGEF2 gene mutation, screening for cardiomyopathy may be indicated.

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