title: Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers.
abstract: BACKGROUND
  Neuropsychiatric disorders are present in up to 90% of patients with Tuberous Sclerosis Complex (TSC), and represent an important issue for families. Autism Spectrum Disorder (ASD) is the most common neurobehavioral disease, affecting up to 61% of patients. The aims of this study were: 1) to assess the prevalence of ASD in a TSC population; 2) to describe the severity of ASD; 3) to identify potential risk factors associated with the development of ASD in TSC patients.
  
  
  METHODS
  We selected 42 individuals over age 4 years with a definite diagnosis of TSC and followed at a TSC clinic in Northern Italy. We collected and reported clinical and genetic data, as well as cognitive level, for each of them. We administered the Social Communication Questionnaire (SCQ) as a reliable screening tool for ASD, and performed comparisons between the average scores and each clinical and genetic feature.
  
  
  RESULTS
  Seventeen out of 42 patients (40.5%) had a score at the SCQ suggestive of ASD (≥15 points). When calculated for each cognitive level category, the average SCQ score tended to be progressively higher in patients with a worse cognitive level, and the number of pathological SCQ scores increased with worsening of intellectual disability. With respect to ASD severity, the scores were equally distributed, indicating that the degree of ASD in TSC patients may have a large variability. By comparing the average SCQ scores with the clinical features, we found statistically significant correlations with epilepsy, seizure onset before age one year, spasms, mutations in TSC2, cognitive level, sleep disorders, and other psychiatric problems, but not with seizure frequency, tubers localization and gender.
  
  
  CONCLUSIONS
  Our study showed a prevalence of ASD of 40.5%, confirming the higher risk for this disorder in patients with TSC. However, the severity seems to have a notable variability in TSC patients. Risk factors for ASD are epilepsy, infantile spams, and mutations in TSC2.
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. aglaia.vignoli@unimi.it.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. francesca.labriola@ao-sanpaolo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: La Briola
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. angela.peron@hotmail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Peron
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. katherine.turner@ao-sanpaolo.it.
authors.forename: Katherine
authors.initials: K
authors.lastname: Turner
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. chiara.vannicola@studenti.unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vannicola
authors.affiliation: Child Neuropsychiatry Unit, AO San Paolo, Milan, Italy. monica.saccani@ao-sanpaolo.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Saccani
authors.affiliation: Child Neuropsychiatry Unit, AO San Paolo, Milan, Italy. elisabetta.magnaghi@unimi.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Magnaghi
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. gf.scornavacca@libero.it.
authors.forename: Giulia Federica
authors.initials: GF
authors.lastname: Scornavacca
authors.affiliation: Child Neuropsychiatry Unit - Epilepsy Center, AO San Paolo, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. maria.canevini@ao-sanpaolo.it.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009483:Neuropsychological Tests; D014402:Tuberous Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers