The use of fetal exome sequencing in prenatal diagnosis: A new ACMG Points to Consider

January 08, 2020

A new Points to Consider document from the ACMG aims to assist referring physicians, laboratory geneticists, genetic counselors and other medical professionals in understanding the complexity and implications of exome sequencing (ES) in prenatal care. Published in ACMG's official journal Genetics in Medicine, the document, "The Use of Fetal Exome Sequencing in Prenatal Diagnosis: A Points to Consider Document of the American College of Medical Genetics and Genomics (ACMG)," is also intended to guide clinical laboratories in the development of protocols and policies related to the increasing use of prenatal exome sequencing.

ACMG President Anthony R. Gregg, MD, MBA, FACOG, FACMG said, "In May 2012, the ACMG Board approved "Points to Consider in the Clinical Application of Genomic Sequencing" and, at that time, they did not recommend fetal genomic sequencing. New data speaks to ACMG's concerns raised at that time. Among these are turnaround time and guidance on identifying and reporting variants of unknown clinical significance. "The Use of Fetal Exome Sequencing in Prenatal Diagnosis: A Points to Consider Document of the American College of Medical Genetics and Genomics (ACMG)" is the first ACMG document devoted exclusively to fetal genomic sequencing and the first to provide a framework that laboratories and clinicians can share. As new information emerges, ACMG creates new guidance, which translates to improved patient care."

Approximately 2-4% of pregnancies are complicated by significant fetal structural anomalies. Given respect for reproductive autonomy, the ACMG document states that "all patients diagnosed with a fetal anomaly should be offered genetic counseling, including review of options for genetic testing." A genetic diagnosis can assist in determining the fetal prognosis and help guide prenatal care, including decisions of reproductive choice, in utero therapy, delivery planning, and neonatal care, and will potentially decrease morbidity and mortality. A prenatal genetic diagnosis may lead to informed genetic counseling for future reproductive options including preimplantation genetic testing, diagnostic prenatal testing or the possible use of donor gametes. Exome sequencing may be considered when a diagnosis cannot be obtained using routine prenatal methods in a fetus with one or more significant structural anomalies. The utilization of exome sequencing is increasing in prenatal care and the new ACMG document provides an in-depth review of its application in the clinical setting for fetuses with sonographic anomalies. "As a trained pediatrician and medical geneticist, one of the most common questions I have heard from parents of a newborn with structural anomalies is: 'What does my child have? What does it mean for my baby? And can this happen again?' To questions regarding diagnosis, prognosis, and recurrence, it is of utmost importance to recognize the underlying cause for the combination of findings first. Fetal exome analysis is now available and has been shown to contribute to earlier diagnosis, which in turn can lead to earlier treatment and better counseling for the family," said ACMG Chief Executive Officer Maximilian Muenke, MD, FACMG.

The comprehensive Points to Consider document includes:The Points to Consider document concludes, "As a new diagnostic test in fetal medicine, ES may be considered when a diagnosis cannot be obtained using routine prenatal methods in a fetus with one or more significant anomalies.... Additional research is needed on patient perspectives of the consent process, effective and appropriate communication of uncertainty, return of results and reinterpretation, and health and economic outcomes."
The full ACMG Points to Consider is published in Genetics in Medicine, the official journal of the ACMG, and available at:

About the American College of Medical Genetics and Genomics (ACMG) and ACMG Foundation

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,400 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG journal. ACMG's website ( offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

American College of Medical Genetics and Genomics

Related Genetic Testing Articles from Brightsurf:

Genetic testing cost effective for newly diagnosed GIST
UC San Diego School of Medicine researchers reported that genetic testing is cost-effective and beneficial for newly diagnosed patients with metastatic gastrointestinal stromal tumors (GIST), a rare type of cancer.

Genetic testing could improve screening for osteoporosis
An international team of scientists has developed a novel genetic measure that could dramatically improve how doctors assess the risk of sustaining a fracture due to osteoporosis or fragility

New recommendations on genetic testing for prostate cancer
Genetic testing for prostate cancer is still not common. New guidelines show why it's important, and which genes to test for.

For acute myeloid leukemia, genetic testing is often worth the wait
New tailored therapies offer exciting prospects for treating acute myeloid leukemia (AML), but taking advantage of them may require waiting a week or more for genetic testing before starting treatment, posing a dilemma for doctors and patients facing this deadly and often fast-moving disease.

Genetic testing among individuals with ASD
Professional medical societies recommend certain genetic tests for individuals with autism spectrum disorder (ASD).

Breast cancer patients to be evaluated for genetic testing
The guidance from the ACMG differs from a consensus guideline issued in February by the American Society of Breast Surgeons, which recommended genetic testing for all newly diagnosed patients with breast cancer.

New technique isolates placental cells for non-invasive genetic testing
A new technique for isolating cells carrying the full fetal genome from cervical swabs could enable doctors to diagnose genetic disorders without using needles to harvest cells from the placenta.

BRCA1/2 genetic testing recommendations still leave issues unresolved
The U.S. Preventive Services Task Force offers new guidelines on BRCA1/2 genetic testing.

Does genetic testing pose psychosocial risks?
For the last quarter century, researchers have been asking whether genetic information might have negative psychosocial effects.

Genetic testing has a data problem; New software can help
As at-home genetic testing becomes more popular, companies are grappling with how to store all the accumulating data and how to process results quickly.

Read More: Genetic Testing News and Genetic Testing Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to