Chromosomal microarray (CMA) is now widely used as first-tier testing for the detection of copy number variants (CNVs) and absence of heterozygosity (AOH) in patients with multiple congenital anomalies (MCA), autism spectrum disorder (ASD), developmental delay (DD), and/or intellectual disability (ID). Chromosome analysis is commonly used to complement CMA in the detection of balanced genomic aberrations. However, the cost-effectiveness and the impact on clinical management of chromosome analysis concomitant with CMA were not well studied, and there is no consensus on how to best utilize these two tests. To assess the clinical utility and cost-effectiveness of chromosome analysis concomitant with CMA in patients with MCA, ASD, DD, and/or ID, we retrospectively analyzed 3,360 postnatal cases for which CMA and concomitant chromosome analysis were performed in the Colorado Genetic Laboratory (CGL) at the University Of Colorado School Of Medicine. Chromosome analysis alone yielded a genetic diagnosis in two patients (0.06%) and contributed additional information to CMA results in 199 (5.92%) cases. The impact of abnormal chromosome results on patient management was primarily related to counseling for reproductive and recurrence risks assessment (101 cases, 3.01%) while a few (5 cases, 0.15%) led to changes in laboratory testing and specialist referral (25 cases, 0.74%). The incremental cost-effectiveness ratio (ICER) of combined testing demonstrated the cost of each informative chromosome finding was significantly higher for patients with clinically insignificant (CI) CMA findings versus clinically significant (CS) CMA results. Our results suggest that a stepwise approach with CMA testing with reflex to chromosome analysis on cases with CS CMA findings is a more cost-effective testing algorithm for patients with MCA, ASD, and/or DD/ID.

中文翻译：

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在美国学术医疗中心对患有全身性疾病的患者进行染色体微阵列检测的临床效用和成本效益分析

染色体微阵列 (CMA) 现已广泛用作检测多发性先天性异常 (MCA)、自闭症谱系障碍 (ASD)、发育迟缓患者的拷贝数变异 (CNV) 和杂合性缺失 (AOH) 的一级检测(DD) 和/或智力障碍 (ID)。染色体分析通常用于补充 CMA 检测平衡基因组畸变。然而，CMA 伴随的染色体分析的成本效益和对临床管理的影响尚未得到很好的研究，对于如何最好地利用这两个测试也没有达成共识。为了评估在 MCA、ASD、DD 和/或 ID 患者中伴随 CMA 进行染色体分析的临床效用和成本效益，我们回顾性分析了 3、科罗拉多大学医学院的科罗拉多遗传实验室 (CGL) 对 360 例产后病例进行了 CMA 和伴随染色体分析。仅染色体分析就对两名患者 (0.06%) 进行了基因诊断，并为 199 例 (5.92%) 病例的 CMA 结果提供了额外信息。染色体异常结果对患者管理的影响主要与生殖和复发风险评估咨询（101 例，3.01%）有关，少数（5 例，0.15%）导致实验室检测和专家转诊（25 例， 0.74%）。联合测试的增量成本效益比 (ICER) 表明，对于临床不显着 (CI) CMA 发现的患者，与临床显着 (CS) CMA 结果相比，每个信息染色体发现的成本显着更高。我们的结果表明，对具有 CS CMA 发现的病例进行反射性染色体分析的 CMA 测试的逐步方法对于患有 MCA、ASD 和/或 DD/ID 的患者来说是一种更具成本效益的测试算法。