Non-invasive prenatal detection of fetal aneuploidies by cell-free DNA, also called non-invasive prenatal testing (NIPT) and non-invasive prenatal screening (NIPS), is a method of non-invasive fetal DNA testing done through a maternal blood sample. NIPT testing for common aneuploidies, microdeletions and sex chromosome disorders is clinically available to patients in Canada. NIPT is a highly sensitive and specific screening test, but is not diagnostic. Even in high-risk populations, there can be false positive NIPT results. Genetic counselling, along with confirmatory testing via amniocentesis or chorionic villus sampling, should be done prior to using the result to impact management of a pregnancy.
Benn P, et al. Ethical and practical challenges in providing noninvasive prenatal testing for chromosome abnormalities: an update. Curr Opin Obstet Gynecol. 2016 Apr;28(2):119-24. PMID: 26938150.
Mersy E, et al. Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012. Hum Reprod Update. 2013 Jul-Aug;19(4):318-29. PMID: 23396607.
Three types of potentially medically-relevant DTC-GT are available: (1) assessment of risk for common multifactorial diseases (e.g., diabetes, etc.); (2) targeted mutation analysis for single gene disorders; and, (3) sequencing. Some DTC-GT companies state that they do not guarantee the accuracy or reliability of their tests. Many of the significant genetic risk and protective factors for multifactorial conditions have not been identified. This leads to greatly divergent risk interpretations between companies, even when performed on the same individual. For targeted mutation analysis and sequencing, the specific test may not include all clinically relevant genes or mutations; resulting in false reassurance. Genetic changes that are only weakly associated with disease may be reported, leading to anxiety or inappropriate additional testing. When making medical decisions based on results of genetic testing, the test should meet the recommendations made by the Canadian College of Medical Geneticists in 2012. Not all DTC-GT meet these recommendations.
Canadian College of Medical Geneticists. Direct-To-Consumer (DTC) Genetic Testing in This Country [Internet]. 2015 Jul 19 [cited 2017 Jan 3].
CCMG Ethics and Public Policy Committee, Nelson TN, Armstrong L, et al. CCMG statement on direct-to-consumer genetic testing. Clin Genet. 2012 Jan;81(1):1-3. PMID: 21943145.
Caulfield T, et al. Direct-to-consumer genetic testing – where should we focus the policy debate? Med J Aust. 2013 May 20;198(9):499-500. PMID: 23682895.
Peikoff, K. I Had My DNA Picture Taken, With Varying Results, New York Times [Internet]. 2013 Dec 30 [cited 2017 Jan 3].
Microarray is the first line test for individuals with intellectual disability/developmental delay without a recognizable syndrome. Indeed, a microarray has a much higher detection rate (15 – 20%) compared to a karyotype (3 – 4%) in individuals presenting for this clinical indication. A karyotype remains important in limited clinical situations where a specific numerical or structural chromosomal syndrome, such as Down syndrome, is suspected.
Michelson DJ, et al. Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011 Oct 25;77(17):1629-35. PMID: 21956720.
Moeschler JB, et al. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics. 2014 Sep;134(3):e903-18. PMID: 25157020.
Newman WG, et al. Array comparative genomic hybridization for diagnosis of developmental delay: an exploratory cost-consequences analysis. Clin Genet. 2007 Mar;71(3):254-9. PMID: 17309648.
Whole exome sequencing (WES) is a powerful test for individuals suspected of having an underlying genetic diagnosis. However, WES increases the likelihood of unexpected findings, which may or may not be clinically significant. Further, due to methodological limitations, WES may not always be the correct test to order as WES will not detect all genetic causes of disease (for example, it will not detect chromosomal structural differences). Both informative and uninformative results can lead to complex patient and family psychosocial repercussions, and could impair future insurability. Genetic counselling facilitates informed decision-making. Given complexity of results, WES should only be ordered after counselling by a qualified health care provider.
Boycott K, et al. The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists. J Med Genet. 2015 Jul;52(7):431-7. PMID: 25951830.
Krabbenborg L, et al. Understanding the Psychosocial Effects of WES Test Results on Parents of Children with Rare Diseases. J Genet Couns. 2016 Dec;25(6):1207-1214. PMID: 27098417.
Sawyer SL, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016 Mar;89(3):275-84. PMID: 26283276.
Carrier testing is primarily useful in the reproductive period to determine the risk of an individual having a child affected by the condition for which testing is being considered. Knowing that a child is a carrier of an X-linked or autosomal recessive condition usually does not alter medical care in the pediatric years since most carriers are unaffected. Thus, in most situations, there is not a medical indication for carrier testing in a child. Undertaking carrier testing of a child violates the right of the child to make his or her own decision about testing and could potentially impair future insurability. An exception could be made for a mature adolescent who may be able to understand the reproductive implications of carrier testing after appropriate genetic counselling.
Borry P, et al. Carrier testing in minors: a systematic review of guidelines and position papers. Eur J Hum Genet. 2006 Feb;14(2):133-8. PMID: 16267502.
Committee on Bioethics, American College of Medical Genetics, et al. Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013 Mar;131(3):620-2. PMID: 23428972.
Guidelines for genetic testing of healthy children. Paediatr Child Health. 2003 Jan;8(1):42-52. PMID: 20011555.