Etiologic yield of autistic spectrum disorders: A prospective study

Authors

  • Agatino Battaglia,

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    • Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, via dei Giacinti 2, 56018 Calambrone (Pisa), Italy.
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    • Dr. Agatino Battaglia is Adjunct Professor of Child Neuropsychiatry at the University of Pisa, Italy; and Adjunct Professor of Pediatrics at the University of Utah Health Sciences Center, Division of Medical Genetics, Department of Pediatrics, Salt Lake City, UT, USA. He is board certified in Clinical Pediatrics and in Neurology. He is Head of the Center for the Study of Congenital Malformation Syndromes, Director of Research in Neuropsychiatric Genetics, and Director of the Clinical Neurophysiology Service at Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, Calambrone (Pisa), Italy. He has a strong research interest in clinical dysmorphology, neuropsychiatric genetics, and clinical neurophysiology. For the years 2002–2005 he was awarded a grant from the Italian Ministry of Health devoted to studying the genetics and neurobiology of autism, and he currently is the on-site director of the multicenter research project “Using European and International Populations to identify Autism Susceptibility Loci” funded by the European Union through contract no. 512158.

  • John C. Carey

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    • Dr. John C. Carey is a Medical Geneticist, Professor of Pediatrics at the University of Utah Health Sciences Center, formerly Chief Division of Medical Genetics, Department of Pediatrics, Salt Lake City, UT, USA. He is the Editor-in-Chief of the American Journal of Medical Genetics, and Vice-Chair Department of Pediatrics.


Abstract

Studies addressing etiologic yield in childhood developmental disabilities have mainly looked at individuals with developmental delay/mental retardation. The few studies addressing the question of etiologic yield in patients with pervasive developmental disorders (PDDs) had a major drawback, in that the enrolled subjects were diagnosed as having the autistic spectrum disorders based only on history and clinical examination, and/or on unspecified instruments. In addition, only some of these patients underwent a complete laboratory evaluation. To investigate the etiologic yield of PDDs, we undertook a large prospective study on subjects selected according to very strict criteria and diagnosed as having PDD based on the present “gold standard” (ADI-R and ADOS-G), and a clinical diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and their first degree relatives participated in this study. These patients were selected from a sample of 236 subjects who had received a clinical diagnosis of PDD at the Stella Maris Institute between March 2002 and 2005. Selection criteria for entering the study were: (1) a diagnosis of PDD (with exclusion of the Rett syndrome) confirmed after the administration of the ADI-R (autism diagnostic interview-revised) and the ADOS-G (autism diagnostic observation schedule-generic). In addition, a clinical diagnosis was made by the child psychiatrist, on the basis of presence or absence of DSM-IV symptoms of autism; (2) chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both biologic parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS, and the remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years 2 months and 12 years 5 months (mean 7.6 years), and there was a marked male preponderance (68/85). All subjects underwent various laboratory studies and neuroimaging. With respect to possible etiologic determination, a detailed history and physical examination in this group of patients with PDD was informative in 10.5% (9/85). HRB karyotype was diagnostic in one, and molecular fragile X studies in one child. Brain MRI was informative in two children (2.3%) with relative macrocrania but no neurological features; and EEG was helpful in one child, identifying a Landau–Kleffner disorder. Audiometry and brainstem auditory evoked potentials (BAEPs) showed a bilateral sensorineural loss in another child. Metabolic evaluation gave normal results in all subjects. The results suggest an evaluation paradigm with reference to etiologic determination for individuals with PDDs that does not presently justify metabolic or neuroimaging on a screening basis. Recurrence risk, treatment implications, and significant and long-lasting emotional relief for the parents suggest that serious consideration be given to clinical genetic examination, genetic testing, EEG study (during wakefulness and sleep), and audiometry, despite a relatively low yield. © 2006 Wiley-Liss, Inc.

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