Genetic investigation for adults with intellectual disability: opportunities and challenges

Purpose of review This review discusses diagnostic genetic assessment for adults with idiopathic intellectual disability, considering the potential yields and limitations of currently available investigations. Recent findings Genome-wide microarray analysis is now a routine diagnostic test. Estimated yields for clinically significant copy number variants in adults with idiopathic intellectual disability are at least 10%. The medical and neuropsychiatric phenotypes of recurrent genomic disorders are being established. Many single gene causes of intellectual disability have been identified, most notably for X-linked intellectual disability. Ascribing causality, determination of recurrence risk, and prognostication for rare or unique variants remain challenging. Summary Clinical evaluation and investigations (both nongenetic and genetic) can yield an aetiological diagnosis for a growing proportion of individuals with intellectual disability. Not all adults with intellectual disability will ever have received such an assessment. Genetic diagnosis can provide an explanation for lifelong disabling cognitive disorder, guide prognosis, and highlight medical comorbidities. A key outcome is clarification of recurrence risk and facilitation of reproductive choices. However, there are limited data on the desirability and acceptability of genetic diagnosis amongst adult patients with intellectual disability and their families, and concern that ethical principles and practices may be changing without scrutiny. The decision to embark on diagnostic review requires careful consideration for each individual.