title: An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits.
abstract: OBJECTIVE
  We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome.
  
  
  METHODS
  Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement.
  
  
  RESULTS
  The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat.
  
  
  CONCLUSIONS
  Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.
authors.affiliation: Swedish Epilepsy Center, University of Washington, Seattle, Washington, U.S.A. Michael.Doherty@Swedish.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Doherty
authors.forename: Ian A
authors.initials: IA
authors.lastname: Glass
authors.forename: Craig L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Phil D
authors.initials: PD
authors.lastname: Cotter
authors.forename: Nate F
authors.initials: NF
authors.lastname: Watson
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.forename: Tom D
authors.initials: TD
authors.lastname: Bird
authors.forename: Don F
authors.initials: DF
authors.lastname: Farrell
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000175:diagnosis / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations; D035781:Siblings; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D005819:Genetic Markers; D009687:Nuclear Proteins; C404411:VCX protein, human