title: Distribution and Within-Family Specificity of Quantitative Autistic Traits in Patients with Neurofibromatosis Type I.
abstract: OBJECTIVE
  To examine the distribution of quantitative autistic traits (QATs) in an independent neurofibromatosis type I (NF1) sample, the relationships between QAT, sex, and attention deficit hyperactivity disorder (ADHD) symptomatology, and to explore evidence for QAT mutational specificity within families.
  
  
  METHODS
  Age-appropriate versions of the Social Responsiveness Scale, second edition and the Conners Adult ADHD Rating Scales were completed for 103 patients with NF1 from the Washington University Neurofibromatosis Center.
  
  
  RESULTS
  Patients with NF1 exhibited a pathologically shifted unimodal distribution for QAT. Forty-four percent of the subjects exhibited a QAT burden at or above 1 SD from the population mean; 13% scored at or above the extreme first percentile of the general population distribution. Elevations in ADHD symptomatology exhibited a distinct bimodal distribution; however, mean ADHD index scores were equivalent in patients who had been diagnosed in the community with ADHD compared with those who had not. We observed striking within-family associations for QAT, reflected by an Social Responsiveness Scale, second edition intraclass correlation of 0.77 in pairings of first degree relatives with NF1.
  
  
  CONCLUSIONS
  Impairments in reciprocal social behavior and attention affect a large proportion of patients with NF1 throughout life and are often clinically unrecognized. Further exploration of genotype-phenotype correlation is strongly warranted for the purpose of gaining insights into mechanisms by which specific mutational variations in the NF1 gene may influence autistic trait severity.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: constantino@wustl.edu.
authors.forename: John N
authors.initials: JN
authors.lastname: Constantino
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: University of Illinois, Chicago, IL.
authors.forename: Kieran
authors.initials: K
authors.lastname: Holzhauer
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
authors.forename: Sayli
authors.initials: S
authors.lastname: Sant
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
authors.forename: Kyna
authors.initials: K
authors.lastname: Long
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Alicia
authors.initials: A
authors.lastname: Vallorani
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
authors.forename: Leena
authors.initials: L
authors.lastname: Malik
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000175:diagnosis*; D001932:Brain Neoplasms / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000150:complications*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012680:Sensitivity and Specificity; D012919:Social Behavior; D014861:Washington; D055815:Young Adult