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Genetic screening and diagnosis: Key advancements and the role of genetic counseling


Preconception and prenatal genetic screening and diagnostic testing for genetic disorders are increasingly complex, with a burgeoning number of testing options and a shift in screening from situations identified as high-risk to more universal considerations. The American College of Obstetricians and Gynecologists now recommends that all patients – regardless of age or risk for chromosomal abnormalities – be offered both screening and diagnostic tests and counseled about the relative benefits and limitations of available tests. These recommendations represent a sea change for obstetrics.

Screening options now include expanded carrier screening that evaluates an individual’s carrier status for multiple conditions at once, regardless of ethnicity, and cell-free DNA screening using fetal DNA found in the maternal circulation. Chromosomal microarray analysis from a chorionic villus sampling or amniocentesis specimen detects tiny copy number variants, and increasingly detailed ultrasound images illuminate anatomic and physiologic anomalies that could not be seen or interpreted as recently as 5 years ago.

These advancements are remarkable, but they require attentive, personalized pre- and posttest genetic counseling. Genetic counselors are critical to this process, helping women and families understand and select screening tools, interpret test results, select diagnostic panels, and make decisions about invasive testing.

Counseling is essential as we seek and utilize genetic information that is no longer binary. It used to be that predictions of normality and abnormality were made with little gray area in between. Now, findings are often on a continuum – one that includes indeterminate results, incidental findings, or variable phenotypes in the case of carrier screening – and genetic diagnosis is increasingly a lattice of details, variable expression, and even effects timing.

Expanded carrier screening

Carrier screening to determine if one or both parents are carriers for an autosomal recessive condition has historically involved a limited number of conditions chosen based on ethnicity. However, research has demonstrated the unreliability of this approach in our multicultural, multiracial society, in which many of our patients have mixed or uncertain race and ethnicity.

Expanded carrier screening is nondirective and takes ethnic background out of the equation. ACOG has moved from advocating ethnic-based screening alone to advising that both ethnic and expanded carrier screening are acceptable strategies and that practices should choose a standard approach to offer and discuss with each patient. (Carrier screening for cystic fibrosis and spinal muscular atrophy are recommended for all patients regardless of ethnicity.)

Detection rates (DR) of screening and dagnostic testing

In any scenario, screening is optimally performed after counseling and prior to pregnancy when patients can fully consider their reproductive options; couples identified to be at 25% risk to have a child with a genetic condition may choose to pursue in-vitro fertilization and preimplantation genetic testing of embryos.

The expanded carrier screening panels offered by laboratories include as many as several hundred conditions, so careful scrutiny of included diseases and selection of a panel is important. We currently use an expanded panel that is restricted to conditions that limit life expectancy, have no treatment, have treatment that is most beneficial when started early, or are associated with intellectual disability.

Some panels look for mutations in genes that are quite common and often benign. Such is the case with the MTHFR gene: 40% of individuals in some populations are carriers, and offspring who inherit mutations in both gene copies are unlikely to have any medical issues at all. Yet, the lay information available on this gene can be confusing and even scary.

Laboratory methodologies should similarly be well understood. Many labs look only for a handful of common mutations in a gene, while others sequence or “read” the entire gene, looking for errors. The latter is more informative, but not all labs that purport to sequence the entire gene are actually doing so.

Patients should understand that, while a negative result significantly reduces their chance of being a carrier for a condition, it does not eliminate the risk. They should also understand that, if their partner is not available for testing or is unwilling to be tested, we will not be able to refine the risk to the pregnancy in the event they are found to be a carrier.


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