title: Periventricular nodular heterotopia and dystonia due to an ARFGEF2 mutation.
abstract: BACKGROUND
  Heterotopias are a neuronal migration disorder caused by extrinsic factors or by genetic mutations. When the location is periventricular, the most frequent genetic cause is the mutation in the "filamin A2 gene", which is X-linked. New genes for periventricular nodular heterotopia with an autosomal inheritance pattern have been recently discovered.
  
  
  METHODS
  We describe two siblings. The girl, who was prenatally diagnosed ventriculomegaly, had delayed development. At 6 months, she had no head control and variable muscle tone, alternating low axial tone with jerking movements. She became microcephalic. Magnetic resonance imaging at 12 months of age revealed enlarged lateral ventricles, periventricular nodular heterotopia, thin corpus callosum, a T2-hyperintensity of the putamen and the thalamus, and a loss of volume of lenticular nucleus. At 18 months, she developed sporadic myoclonic seizures that were well controlled with valproic acid. Her younger brother also developed progressive microcephaly and psychomotor delay by 6 months. He exhibited axial hypotonia with a prominent dystonic-athetoid component. Magnetic resonance imaging at 15 months of age revealed asymmetric ventriculomegaly plus diffuse nodules lining the temporal horns, a thin corpus callosum, and hyperintensity signal in putamens. He had no seizures.
  
  
  RESULTS
  Because of the association of microcephaly, developmental delay with dystonic movements, the imaging results, and the probable autosomal recessive inheritance pattern, genetic analysis was requested. This detected a homozygous nonsense mutation in ARFGEF2 gene, at the DNA level c.388C>T in exon 4.
  
  
  CONCLUSIONS
  The presence of dyskinetic movements in individuals with acquired microcephaly could be a manifestation of periventricular nodular heterotopia due to ARFGEF2 mutation.
authors.affiliation: Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Eduardo Jesús
authors.initials: EJ
authors.lastname: Bardón-Cancho
authors.affiliation: Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Muñoz-Jiménez
authors.affiliation: Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Section of Neuropediatrics, Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Electronic address: vazquezlopezmaria@gmail.com.
authors.forename: María
authors.initials: M
authors.lastname: Vázquez-López
authors.affiliation: Section of Pediatric Radiology, Department of Radiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Ruíz-Martín
authors.affiliation: Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: García-Morín
authors.affiliation: Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Section of Neuropediatrics, Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Barredo-Valderrama
mesh_terms: D001921:Brain / Q000473:pathology; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D020821:Dystonic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D054091:Periventricular Nodular Heterotopia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D035781:Siblings
chemical_list: C119088:ARFGEF2 protein, human; D018389:Codon, Nonsense; D020662:Guanine Nucleotide Exchange Factors
keywords: cerebral palsy; dyskinesia; extrapyramidal; heterotopia; periventricular; psychomotor delay; putamen; “ARFGEF2” mutation