Our suggested approach to genetic testing in children with unexplained intellectual disability

This figure summarizes our suggested approach to genetic testing for children with unexplained ID (ie, in whom no specific disorder is clinically suspected based upon physical examination, clinical history, or other findings). It represents the approach at the author's institution. However, practice varies and other experts may prefer a different sequence for testing. Prior to undergoing genetic testing, all children with ID should have an initial evaluation that includes the following:

• A detailed medical and developmental history (including prenatal and birth history)
• A detailed family history (including history of ID and neonatal or fetal deaths)
• Complete physical examination (including detailed neurologic examination and evaluation for dysmorphic features)
• Review of newborn screening results
• Lead screening if there are relevant environmental exposures
• Selective use of neuroimaging (eg, for children with seizures, microcephaly or macrocephaly, progressive or degenerative neurologic symptoms, or focal neurologic deficits)

For children with dysmorphic features or other characteristics that suggest a particular syndrome or disorder, targeted testing should be performed to confirm or exclude that specific disorder as the initial step in the evaluation (eg, testing for fragile X syndrome in males with ID and characteristic physical findings such as macrocephaly and large ears). Broader genetic testing for unexplained ID should be offered if testing for the specific disorder is nondiagnostic or if no specific disorder is clinically suspected. Referral to a pediatric clinical geneticist is advised when pursuing genetic testing for unexplained ID to guide the evaluation and to facilitate genetic counseling for the family. Comprehensive pretest counseling should incorporate clinical judgment and parent/caregiver preferences and consent. This figure is intended for use in conjunction with additional UpToDate content. Refer to UpToDate's topics on ID in children for additional details.