Etiologic yield of autistic spectrum disorders: a prospective study

Area of Science:

• Neuroscience
• Genetics
• Developmental Pediatrics

Background:

• Previous studies on etiologic yield in developmental disabilities often focused on developmental delay, with limited evaluation of pervasive developmental disorders (PDDs).
• Existing research on PDDs frequently involved subjects diagnosed based on history and clinical examination, or unspecified instruments, with incomplete laboratory evaluations.
• This study addresses the limitations by employing strict diagnostic criteria and comprehensive evaluations for PDDs.

Purpose of the Study:

• To investigate the etiologic yield of pervasive developmental disorders (PDDs) using a rigorous diagnostic approach.
• To establish an evidence-based evaluation paradigm for determining the etiology of PDDs in children.
• To assess the utility of various diagnostic tools, including genetic testing, neuroimaging, and audiology, in identifying the cause of PDDs.

Main Methods:

• A prospective study involving 85 patients diagnosed with PDDs (autism, PDD-NOS, Asperger syndrome) based on DSM-IV criteria, ADI-R, and ADOS-G, with IQ > 30 and aged 4-18 years.
• Patients underwent detailed history, physical examination, karyotype, fragile X studies, brain MRI, EEG, audiometry, and BAEPs.
• Exclusion criteria included Rett syndrome; availability of both biological parents was required.

Main Results:

• Clinical history and physical examination yielded a diagnosis in 10.5% of patients.
• Genetic testing (karyotype, fragile X) was diagnostic in two children.
• Neuroimaging (MRI) was informative in 2.3% of cases, identifying macrocrania; EEG identified one case of Landau-Kleffner disorder; audiology revealed sensorineural loss in one child.
• Metabolic evaluations were normal in all subjects.

Conclusions:

• Current metabolic and neuroimaging screenings have a low yield for identifying the etiology of PDDs and are not recommended on a screening basis.
• Clinical genetic examination, genetic testing, EEG, and audiometry are recommended due to their potential to inform recurrence risk, treatment, and provide parental relief, despite a relatively low overall diagnostic yield.
• The findings support a targeted evaluation approach for PDDs, prioritizing genetic and audiological assessments over broad metabolic or neuroimaging screening.