title: Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion.
abstract: BACKGROUND
  Periventricular heterotopia (PH) is an etiologically heterogeneous disorder characterized by nodules of neurons ectopically placed along the lateral ventricles. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. At present, two genes have been identified to cause PH when mutated. Mutations in FLNA (Xq28) and ARFGEF2 (20q13) are responsible for X-linked bilateral PH and a rare autosomal recessive form of PH with microcephaly. Chromosomal rearrangements involving the 1p36, 5p15, and 7q11 regions have also been reported in association with PH but the genes implicated remain unknown. Fourteen additional distinct anatomoclinical PH syndromes have been described, but no genetic insights into their causes have been gleaned.
  
  
  METHODS
  We report the clinical and imaging features of three unrelated patients with epilepsy, mental retardation, and bilateral PH in the walls of the temporal horns of the lateral ventricles, associated with a de novo deletion of the 5q14.3-15 region. We used microarray-based comparative genomic hybridization to define the boundaries of the deletions.
  
  
  RESULTS
  The three patients shared a common deleted region spanning 5.8 Mb and containing 14 candidate genes.
  
  
  CONCLUSIONS
  We identified a new syndrome featuring bilateral periventricular heterotopia (PH), mental retardation, and epilepsy, mapping to chromosome 5q14.3-q15. This observation reinforces the extreme clinical and genetic heterogeneity of PH. Array comparative genomic hybridization is a powerful diagnostic tool for characterizing causative chromosomal rearrangements of limited size, identifying potential candidate genes for, and improving genetic counseling in, malformations of cortical development.
authors.affiliation: Pediatric Neurology Unit and Laboratories, Children's Hospital A Meyer-University of Florence, Firenze, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cardoso
authors.forename: A
authors.initials: A
authors.lastname: Boys
authors.forename: E
authors.initials: E
authors.lastname: Parrini
authors.forename: C
authors.initials: C
authors.lastname: Mignon-Ravix
authors.forename: J M
authors.initials: JM
authors.lastname: McMahon
authors.forename: S
authors.initials: S
authors.lastname: Khantane
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: E
authors.initials: E
authors.lastname: Pallesi
authors.forename: C
authors.initials: C
authors.lastname: Missirian
authors.forename: O
authors.initials: O
authors.lastname: Zuffardi
authors.forename: F
authors.initials: F
authors.lastname: Novara
authors.forename: L
authors.initials: L
authors.lastname: Villard
authors.forename: S
authors.initials: S
authors.lastname: Giglio
authors.forename: B
authors.initials: B
authors.lastname: Chabrol
authors.forename: H R
authors.initials: HR
authors.lastname: Slater
authors.forename: A
authors.initials: A
authors.lastname: Moncla
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: R
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054091:Periventricular Nodular Heterotopia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult