Laboratory testing for preconception/prenatal carrier screening: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Carrier screening has historically assessed a relatively small number of autosomal recessive and X-linked conditions selected based on frequency in a specific subpopulation and association with severe morbidity or mortality. Advances in genomic technologies enable simultaneous screening of individuals for several conditions. The American College of Medical Genetics and Genomics recently published a clinical practice resource that presents a framework when offering screening for autosomal recessive and X-linked conditions during pregnancy and preconception and recommends a tier-based approach when considering the number of conditions to screen for and their frequency within the US population in general. This laboratory technical standard aims to complement the practice resource and to put forth considerations for clinical laboratories and clinicians who offer preconception/prenatal carrier screening.

Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG).

PURPOSE: This workgroup aimed to develop an evidence-based clinical practice guideline for the use of noninvasive prenatal screening (NIPS) for pregnant individuals at general risk for fetal trisomy 21, trisomy 18, or trisomy 13 and to evaluate the utility of NIPS for other chromosomal disorders. METHODS: The NIPS Evidence-Based Guideline Work Group (n = 7) relied on the results from the recent American College of Medical Genetics and Genomics (ACMG) systematic review to form the evidentiary basis of this guideline. Workgroup members used the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework to draft recommendations. The guideline underwent extensive internal and external peer review with a public comment period before approval by the ACMG Board of Directors. RESULTS: Evidence consistently demonstrated improved accuracy of NIPS compared with traditional screening methods for trisomies 21, 18, and 13 in singleton and twin gestations. Identification of rare autosomal trisomies and other microdeletion syndromes with NIPS is an emerging area of interest. CONCLUSION: ACMG strongly recommends NIPS over traditional screening methods for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.

Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).

Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay-Sachs disease in the Ashkenazi Jewish population; sickle cell disease in Black individuals). Cystic fibrosis was the first medical condition for which panethnic screening was recommended, followed by spinal muscular atrophy. Next-generation sequencing allows low cost and high throughput identification of sequence variants across many genes simultaneously. Since the phrase "expanded carrier screening" is nonspecific, there is a need to define carrier screening processes in a way that will allow equitable opportunity for patients to learn their reproductive risks using next-generation sequencing technology. An improved understanding of this risk allows patients to make informed reproductive decisions. Reproductive decision making is the established metric for clinical utility of population-based carrier screening. Furthermore, standardization of the screening approach will facilitate testing consistency. This practice resource reviews the current status of carrier screening, provides answers to some of the emerging questions, and recommends a consistent and equitable approach for offering carrier screening to all individuals during pregnancy or preconception.

Role of the 3-Vessel and Trachea View in Antenatal Detection of Tetralogy of Fallot.

Prenatal diagnosis of tetralogy of Fallot remains less frequent compared to other major congenital heart defects. In this study, we examined how often the 3-vessel and trachea view was abnormal in a large series of prenatally diagnosed cases of tetralogy of Fallot. In addition, we compared its sensitivity to that of the traditional outflow tract views for detection of tetralogy of Fallot. We found that both views were abnormal in all fetuses with tetralogy of Fallot, showing reversed aortic-to-pulmonary valve and aortic arch isthmus-to-ductus arteriosus ratios in the outflow tract and 3-vessel and trachea views, respectively. However, as a single measured marker, the enlarged aortic arch isthmus on the 3-vessel and trachea view appears to be the most sensitive for tetralogy of Fallot.

3-D ultrasound of the fetal ear and fetal autosomal trisomies: a pilot study of a new screening protocol.

OBJECTIVE: We hypothesize that the rotation of the ear in fetuses with common autosomal trisomies will be markedly different from euploid fetuses and amenable to detection by 3-D ultrasound in the render mode. METHODS: Study participants (10 weeks 4 days through 19 weeks 0 days) underwent a 3-D rendering of the fetal face and ear along with other biometric measurements prior to invasive testing. RESULTS: Of the 348 patients who underwent chorionic villi sampling (CVS) (n = 208) or amniocentesis (n = 140), 18 were diagnosed with trisomy 21, 4 with trisomy 18, and 1 with trisomy 13. Mean gestational age was 12 weeks 6 days (range: 10 weeks 6 days to 19 weeks 0 days). Ear angles were obtained in all cases; the time to obtain this angle ranged from 5 to 25 min. Thirty-two fetuses were found to have an abnormal ear angle with 23 of the 32 characterized by one of the aforementioned trisomies. CONCLUSIONS: These findings support the potential of this technique to provide valuable information in the identification of an increased-risk population. Prospective studies are needed to confirm the value of this screening modality as well as to assess its facility and ability to be incorporated into routine obstetrical practice.

Carrier screening for cystic fibrosis.

Cystic fibrosis is the first genetic disorder for which universal screening of preconceptional or prenatal patients became a component of standard prenatal care. The molecular genetics and mutation profile of the CFTR gene are complex, with a wide range of phenotypic consequences. Carrier screening can facilitate risk assessment for prospective parents to have an affected offspring, although there remains a small residual risk for carrying a mutation even with a negative screening result. There are ethnic differences with respect to disease incidence and effectiveness of carrier testing, which may complicate counseling.