title: Autism spectrum disorder phenotype and intellectual disability in females with epilepsy and PCDH-19 mutations.
abstract: Autism features and various degrees of cognitive deficit are reported in patients with PCDH-19 mutations and epilepsy. Autism spectrum disorder (ASD) and, often, cognitive profile are usually assessed clinically. We studied autism phenotype and cognitive outcome in a series of patients using standardized tools for development and ASD. We aimed to describe the phenotype of ASD in this series and to understand whether ASD is strictly linked to intellectual disability (ID) or is present as a comorbidity.
  
  
  
  Eight females aged 5 to 17years old with PCDH-19 mutations and epilepsy were recruited. For ASD diagnosis, the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnosis Observation Schedule (ADOS) were administered. Patients underwent a neuropsychological examination with tests measuring global intellectual efficiency (WPPSI-III and WISC-IV), language, and executive and social cognition abilities. Parental adaptive behavioral questionnaires were also obtained (VABS, CBCL, and BRIEF).
  
  
  
  Six out of eight patients presented with ASD and ID. Two patients had neither ASD nor ID, and both had the latest age of onset for their epilepsy. All cognitive functions were deficient, but theory-of-mind abilities compared to other cognitive features were even impaired. Features of ASD lacked major repetitive and stereotyped behaviors and show some differences with the classical ASD features related to ID.
  
  
  
  Our results show a large spectrum of ID and a very high rate of ASD in patients with epilepsy and PCDH-19 mutations. Autism spectrum disorder seems to be a genuine comorbidity, more than a consequence of ID. It highlights the importance of standardized psychiatric and cognitive evaluation in order to establish a tailored rehabilitation program.
authors.affiliation: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France; INSERM U1129, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Breuillard
authors.affiliation: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Leunen
authors.affiliation: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France; INSERM U1129, Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Chemaly
authors.affiliation: INSERM U1129, Paris, France; Paris Descartes University, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Auclair
authors.affiliation: Department of Pediatric Neurology, Raymond Poincaré Hospital, Paris, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Pinard
authors.affiliation: Clinical Electrophysiology Unit, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.affiliation: INSERM U1129, Paris, France; Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.affiliation: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ouss
authors.affiliation: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Paris Descartes University, Necker Enfants Malades Hospital, Paris, France; INSERM U1129, Paris, France; Paris Descartes University, France. Electronic address: rima.nabbout@aphp.fr.
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000150:complications* / Q000523:psychology*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics* / Q000523:psychology*; D056344:Executive Function; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000523:psychology*; D007802:Language; D009154:Mutation / Q000235:genetics; D010290:Parents / Q000523:psychology; D000091363:Protocadherins; D011569:Psychiatric Status Rating Scales; D012919:Social Behavior; D014888:Wechsler Scales
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins
keywords: Autism spectrum disorder; Children; Comorbidity; Developmental outcome; Epilepsy; Intellectual disability; PCDH-19 mutations