Laboratory Stewardship Rescues Misordered Familial Targeted Cytogenetic Testing Following Proband Genomic Testing:...

Laboratory genetic counselors (GCs) in cytogenetics oversee a laboratory stewardship (LS) program to review the appropriateness of incoming test orders, which saves both time and healthcare resources. This is especially important for familial cytogenetic testing performed after proband genomic testing, since appropriate testing methodology may vary between families and among family members. We describe three inappropriate orders for familial cytogenetic testing performed after proband genomic testing that were identified and corrected because of the LS process at ARUP Laboratories. Review of familial testing using an LS program avoids false-negative results in at-risk relatives and shortens the time to provide accurate results, enabling relatives to make informed clinical management decisions. This series highlights the importance of seeking genetic advice prior to submitting familial testing samples and including the proband's test results to help the laboratory confirm the appropriateness of test orders. Structural variants (SVs) are identified by proband chromosome analysis, genomic microarray (GMA), and genome sequencing. Healthcare providers without specialized genetics expertise may not realize that SVs can be cryptic by karyotype or undetectable by GMA (when balanced), and that standard FISH probes may fail to detect SVs due to FISH probe localization not spanning the abnormality, even when the FISH probe is designed to target the patient's condition. This series illustrates the benefits of a routine laboratory LS program for familial cytogenetic testing, particularly when cryptic SVs are involved.