title: The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis.
abstract: BACKGROUND
  Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients.
  
  
  METHODS
  The study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals.
  
  
  RESULTS
  One known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria.
  
  
  CONCLUSIONS
  These findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome.
authors: Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Campus Forschung, Martinistraße 52, 20246 Hamburg, Germany.
authors: Fanny
authors: F
authors: Kortüm
authors: Soma
authors: S
authors: Das
authors: Max
authors: M
authors: Flindt
authors: Deborah J
authors: DJ
authors: Morris-Rosendahl
authors: Irina
authors: I
authors: Stefanova
authors: Amy
authors: A
authors: Goldstein
authors: Denise
authors: D
authors: Horn
authors: Eva
authors: E
authors: Klopocki
authors: Gerhard
authors: G
authors: Kluger
authors: Peter
authors: P
authors: Martin
authors: Anita
authors: A
authors: Rauch
authors: Agathe
authors: A
authors: Roumer
authors: Sulagna
authors: S
authors: Saitta
authors: Laurence E
authors: LE
authors: Walsh
authors: Dagmar
authors: D
authors: Wieczorek
authors: Gökhan
authors: G
authors: Uyanik
authors: Kerstin
authors: K
authors: Kutsche
authors: William B
authors: WB
authors: Dobyns
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000737:chemistry*; D055028:Comparative Genomic Hybridization; D003337:Corpus Callosum / Q000473:pathology; D020820:Dyskinesias / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008831:Microcephaly / Q000235:genetics; D008969:Molecular Sequence Data; D058889:Molecular Typing; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D015518:Rett Syndrome / Q000145:classification* / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins