Department of Medical Genetics, University of Cambridge, UK.
Curr Opin Neurol. 2012 Apr;25(2):150-8. doi: 10.1097/WCO.0b013e328351820e.
This review discusses diagnostic genetic assessment for adults with idiopathic intellectual disability, considering the potential yields and limitations of currently available investigations.
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.
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.
本篇综述讨论了对特发性智力障碍成人进行诊断性遗传评估，同时考虑了当前可用检查的潜在获益和局限性。
全基因组微阵列分析现在是常规诊断测试。在特发性智力障碍成人中，临床显著拷贝数变异的预估检出率至少为 10%。复发性基因组疾病的医学和神经精神表型正在建立中。许多智力障碍的单基因病因已被确定，尤其是 X 连锁智力障碍。确定罕见或独特变异的因果关系、复发风险和预后仍然具有挑战性。
临床评估和检查（包括非遗传和遗传检查）可以为越来越多的智力障碍患者确定病因诊断。并非所有智力障碍成人都曾接受过此类评估。遗传诊断可为终身致残性认知障碍提供解释，指导预后，并突出医疗合并症。一个关键的结果是阐明复发风险，并为生殖选择提供便利。然而，智力障碍成人患者及其家属对遗传诊断的可取性和可接受性的数据有限，而且人们担心伦理原则和实践可能在未经审查的情况下发生变化。是否进行诊断性检查需要对每个个体进行仔细考虑。
