Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA.
Genetics Counseling Program, Department of Genetics, University of Colorado School of Medicine, Aurora, CO, USA.
J Genet Couns. 2022 Apr;31(2):364-374. doi: 10.1002/jgc4.1496. Epub 2021 Aug 16.
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.
染色体微阵列（CMA）现已广泛应用于检测多种先天性异常（MCA）、自闭症谱系障碍（ASD）、发育迟缓（DD）和/或智力障碍（ID）患者的拷贝数变异（CNV）和杂合性缺失（AOH）。染色体分析常用于补充 CMA 以检测平衡基因组异常。然而，染色体分析与 CMA 同时进行的成本效益及其对临床管理的影响尚未得到很好的研究，如何最好地利用这两种测试也没有共识。为了评估 CMA 联合染色体分析在 MCA、ASD、DD 和/或 ID 患者中的临床效用和成本效益，我们回顾性分析了在科罗拉多大学医学院 Colorado Genetic Laboratory（CGL）进行 CMA 检测和同时进行染色体分析的 3360 例出生后患者。单独的染色体分析仅在 2 例患者（0.06%）中得出遗传诊断，并在 199 例（5.92%）病例中对 CMA 结果提供了额外信息。异常染色体结果对患者管理的影响主要与生育和复发风险评估咨询有关（101 例，3.01%），而少数（5 例，0.15%）则导致实验室检测和专科转诊的改变（25 例，0.74%）。联合检测的增量成本效益比（ICER）表明，对于具有临床意义（CS）CMA 结果的患者，每个有意义的染色体发现的成本明显高于具有临床意义（CI）CMA 发现的患者。我们的结果表明，对于 MCA、ASD 和/或 DD/ID 患者，CMA 检测加 CS CMA 结果的染色体分析是一种更具成本效益的检测算法。
