Objective To describe uptake of carrier screening by male reproductive partners of prenatal and preconception patients. Methods A retrospective database review of all prenatal and preconception patients seen for genetic counseling in Maternal Fetal Medicine clinics was performed. Descriptive statistics and chi‐square analysis were used on the data set. Results Within the study period, 6087 patients were seen for genetic counseling, of whom 661 were identified as a carrier of an autosomal recessive disorder by their referring provider or genetic counselor. Despite guidelines recommending partner testing for risk clarification when a woman is known to be a carrier of an autosomal recessive condition, only 41.5% male partners elected carrier screening to clarify the couple's reproductive risk, with a majority of males (75%) having screening consecutively. Of all assessed variables, the only significant predictors of male carrier screening uptake were female parity and earlier gestational age (p < .0001, and p = .001, respectively). Conclusion With less than half of male partners pursuing carrier screening when indicated, its utility becomes severely diminished. More research is needed to explore reasons why males elect or decline carrier screening.

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome primarily defined by increased risk for colorectal and uterine cancers. Individuals with germline pathogenic variants in the mismatch repair (MMR) genes (MLH1, MSH2/EPCAM, MSH6, and PMS2) are diagnosed with LS and recommended high-risk screening protocols to increase prevention and early detection of LS-related cancers. Tumor testing can help identify those at high risk for LS, but sometimes creates uncertainty with discordant screening and germline results, or unexplained mismatch repair deficiency (UMMRD). Somatic testing for MMR genes may help resolve UMMRD, potentially clarifying LS status and modifying cancer surveillance. However, guidelines for such testing are currently limited. This survey of cancer genetic counselors (GCs) aimed to examine current versus preferred ordering practices and interpretation of somatic MMR testing results in LS evaluation. Two hundred eligible GCs practicing in the United States and Canada were recruited from the National Society of Genetic Counselors. Participants answered questions regarding ordering practices, barriers to somatic MMR testing, theoretical scenarios, and desire for further guidelines. Statistical analysis was performed using chi-square, Fisher's exact, and Wilcoxon rank-sum tests, while themes were identified from free-text responses. Most respondents did not include somatic MMR testing in the LS work-up, despite three-quarters reporting they were 'somewhat comfortable' or 'extremely comfortable' with interpreting these results. Approximately half of participants indicated interest in ordering concurrent somatic MMR and germline testing for each of the four theoretical scenarios. Over three-quarters of individuals reported barriers to ordering somatic MMR testing, with cost and coordinating tissue samples most commonly cited. The frequently reported laboratory-and insurance-related barriers may contribute to the gap between preferred and current ordering practices for somatic MMR testing. Nearly all respondents endorsed additional guidelines for this testing, which could reduce barriers and inform screening recommendations for patients with UMMRD and their family members.

The uptake of CMA significantly increased over a 4-year period at a large academic institution. Women with ultrasound indications, specifically structural abnormalities, are the most likely to elect CMA.

Objective: Explore the utility of expanded carrier screening in evaluating heritable causes of congenital anomalies detected by prenatal ultrasound.Method: A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. These were used to determine if expanded carrier screening could have determined the etiology prior to delivery. Additionally, recessive and Xlinked conditions on clinically available carrier screening panels were evaluated to determine the number of conditions associated with abnormal ultrasound findings.Results: Our retrospective chart review found 222 patients with genetic etiologies, including eight unique autosomal recessive conditions and six X-linked conditions in the 23% who underwent exome sequencing. Of these 14 unique conditions detected, three were included on a list of 271 conditions for which screening was available in 2019 and five were included on a 500 condition panel available in 2020.A literature review was performed on the list of 271 conditions and 88 were reported to be associated with one or more ultrasound abnormalities. Conclusion:This study demonstrates limited but potential utility for expanded carrier screening to determine the underlying etiology of congenital anomalies. Key points What's already known about this topic?� Expanded carrier screening is an established general population screening option.� Diagnostic testing via amniocentesis or CVS with chromosome microarray is recommended in pregnancies diagnosed with congenital anomalies via ultrasound.� Diagnosis of single gene disorders typically require additional testing beyond chromosome microarray.� This study evaluates the utility of expanded carrier screening as a risk assessment tool for pregnancies with congenital anomalies.

Routine screening with prenatal ultrasound is now recommended in all pregnancies due in part to the 3% risk for congenital anomalies. Detected anomalies that receive a prenatal diagnosis can benefit from more targeted prenatal and postnatal care recommendations. In addition to cell-free DNA screening for aneuploidy, an additional noninvasive method for evaluating a pregnancy in search of possible single-gene disorders is expanded carrier screening (ECS). This study's aim was to evaluate whether ECS is of utility in assessing fetal ultrasound abnormalities.The study was based on a retrospective chart review of genetic testing results in infants born with congenital structural abnormalities between January 1, 2014 and December 31, 2017. The authors collected genetic testing results to determine whether ECS would potentially have helped point to the genetic diagnosis. Inclusion requirements included patients who underwent evaluation by a medical geneticist within the first 6 months of life due to the presence of a structural abnormality potentially detectable by prenatal ultrasound. Infants diagnosed with an X-linked or autosomal recessive disorder were included to determine whether the disorder would have been detected using a clinically available ECS panel. The authors considered 2 different ECS panels: one was available in 2017 and included 271 conditions, and the other was available after 2020 and included 500 autosomal recessive and X-linked conditions. In addition, after the composition of the initial list of 271 autosomal recessive and X-linked conditions, a literature search in both PubMed and OMIM also yielded further data of potential phenotypes for analysis.The review revealed that 931 subjects met inclusion criteria; after exclusion of those infants that did not have a structural anomaly potentially detectable by prenatal ultrasound, those that did not have genetic testing, and those with a negative result, there were 222 infants with positive genetic results that were thought to have likely caused the phenotype. Among these, 42 (18.9%) were specifically diagnosed with single-gene disorders potentially detectable by carrier screening, including 8 unique autosomal recessive conditions and 6 X-linked conditions. Of the 14 unique genetic conditions, 3 were available on the initial 271-condition panel, whereas 5 disorders could have been detected by ECS in the 500-condition panel. Overall, 222 patients with a structural abnormality identifiable by prenatal ultrasound had a genetic diagnosis. Of these, 6 cases (2.7%) were detectable using a 500-condition ECS panels, compared with 4 (1.8%) with a 271-condition panel. Among the 41 cases of single-gene disorders, a 500-condition ECS panel could potentially have detected 14.6% of cases, whereas a 271-condition panel could have detected 9.8%.Ultimately, the data demonstrated that the utility of ECS in detecting single-gene disorders seemed to be very limited when compared with exome sequencing. However, ECS could be a useful tool for detecting conditions that are ...

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