title: Clinical variability and novel neurodevelopmental findings in 49, XXXXY syndrome.
abstract: 49, XXXXY is a rare chromosomal syndrome due to double nondisjunction of the replicating X chromosome. Considered a severe variant of XXY or Klinefelter syndrome, boys with this chromosome constitution are assumed to have severe mental retardation (MR) in addition to craniofacial, genital, endocrine, and heart abnormalities. Here, we present a multidisciplinary analysis including the clinical and neurobehavioral aspects of this condition in 20 boys with 49, XXXXY who share a common phenotype and neurobehavioral profile. The phenotypic presentation of the boys with 49, XXXXY shares some characteristics with 47, XXY, but there are also other unique and distinctive features. Previously unappreciated intact nonverbal skills are evident in conjunction with moderate to severe developmental dyspraxia. Variability in clinical and cognitive functioning may reflect skewed X inactivation, mosaicism, or other factors that warrant further investigation.
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, District of Columbia 20010, USA. agropman@cnmc.org
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.forename: Alan
authors.initials: A
authors.lastname: Rogol
authors.forename: Ilene
authors.initials: I
authors.lastname: Fennoy
authors.forename: Teresa
authors.initials: T
authors.lastname: Sadeghin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sinn
authors.forename: Robert
authors.initials: R
authors.lastname: Jameson
authors.forename: Francine
authors.initials: F
authors.lastname: Mitchell
authors.forename: Jaye
authors.initials: J
authors.lastname: Clabaugh
authors.forename: Margaret
authors.initials: M
authors.lastname: Lutz-Armstrong
authors.forename: Carole A
authors.initials: CA
authors.lastname: Samango-Sprouse
mesh_terms: D000293:Adolescent; D000782:Aneuploidy; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D003071:Cognition; D006801:Humans; D007223:Infant; D007713:Klinefelter Syndrome / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D011596:Psychomotor Disorders / Q000503:physiopathology* / Q000523:psychology; D013577:Syndrome