Moeschler John B
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Semin Pediatr Neurol. 2008 Mar;15(1):2-9. doi: 10.1016/j.spen.2008.01.002.
All children with an intellectual disability (mental retardation) or global developmental delay should have a comprehensive evaluation to establish the etiology of the disability. A specific etiologic diagnosis offers the opportunity to discuss treatment, prognosis, and genetic recurrence risk. A diagnosis also avoids unnecessary testing and can lead to opportunities for improved health and functional outcomes. The key elements of the diagnostic evaluation are the medical and developmental history, 3-generation family history, dysmorphologic examination, neurologic examination, and judicious use of the laboratory and neuroimaging. All published guidelines for the evaluation of children with intellectual disability acknowledge that there is a substantial percentage of patients who are undiagnosed after a comprehensive evaluation and who deserve ongoing follow-up for the purpose of establishing a diagnosis. Recently, studies of the clinical application of array comparative genomic hybridization (aCGH) to individuals with intellectual disability indicate that this approach provides a diagnosis in as much as 10% of patients and that this technique is replacing the use of fluorescent in situ hybridization for subtelomere imbalances now used for such patients when the standard karyotype is normal. The literature suggests that history and examination by an expert clinician will lead to a diagnosis in 2 of 3 patients in whom a diagnosis is made. Laboratory studies alone, including neuroimaging, provide a diagnosis in the remaining one third. The approach to the evaluation of the patient in whom an etiologic diagnosis is not suspected after the history and physical examinations includes a standard karyotype, Fragile X molecular genetic testing, aCGH, and neuroimaging, based on the evidence to date. One can expect rapid changes in the microarray technology in the near future.
所有智力残疾（智力发育迟缓）或全面发育迟缓的儿童都应进行全面评估，以确定残疾的病因。明确的病因诊断有助于讨论治疗、预后和遗传复发风险。诊断还可避免不必要的检查，并能带来改善健康和功能结局的机会。诊断评估的关键要素包括医学和发育史、三代家族史、畸形学检查、神经学检查，以及合理运用实验室检查和神经影像学检查。所有已发表的关于智力残疾儿童评估的指南都承认，有相当比例的患者在全面评估后仍未确诊，需要持续随访以明确诊断。最近，关于将阵列比较基因组杂交（aCGH）应用于智力残疾个体的临床研究表明，这种方法能为多达10%的患者做出诊断，并且在标准核型正常时，该技术正在取代用于此类患者的荧光原位杂交技术来检测亚端粒失衡。文献表明，由专业临床医生进行的病史询问和检查能为三分之二已确诊的患者做出诊断。仅靠实验室检查，包括神经影像学检查，能为其余三分之一的患者做出诊断。根据目前的证据，对于在病史和体格检查后未怀疑有病因诊断的患者，评估方法包括标准核型分析、脆性X分子遗传学检测、aCGH和神经影像学检查。预计在不久的将来，微阵列技术会有快速发展。
