TABLE 8

Genetic Etiologic Investigations in Patients With ASD

StepGenetic Etiologic Investigations
1Consider referral for pediatric genetics evaluation
2Comprehensive history (including 3-generation family history with emphasis on individuals with ASD and other developmental, behavioral and/or psychiatric, and neurologic diagnoses)
Physical examination (including dysmorphology, growth parameters [including head circumference], and skin examination)
 • If syndrome diagnosis or metabolic disorder is suspected, go back to step 1 (genetics and/or metabolism referral) and/or order the appropriate targeted testing
 • Otherwise, proceed to step 3
3Laboratory studies
 • Discuss and offer CMA analysis
 • Discuss and offer fragile X analysis; if family history is suggestive of sex-linked intellectual disabilities, refer to genetics for additional testing
 • If patient is a girl, consider evaluation for Rett syndrome, MECP2 testing
 • If these studies do not reveal the etiology, proceed to step 4
4Consider referral to genetics, workup might include WES
  • Adapted from Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15(5):399–407; Srivastava S, Love-Nichols JA, Dies KA, et al; NDD Exome Scoping Review Work Group. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders [published online ahead of print June 11, 2019]. Genet Med. and Shevell M, Ashwal S, Donley D, et al; Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2003;60(3):367–380.