Correspondence on “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)” by Gregg et al

Righetti, Sarah; Dive, Lisa; Archibald, Alison D; Freeman, Lucinda; McClaren, Belinda; Kanga-Parabia, A; Delatycki, Martin B.; Laing, Nigel G.; Kirk, Edwin P.; Newson, Ainsley J

doi:10.1016/j.gim.2022.01.007

Cited by 10 publications

(10 citation statements)

References 14 publications

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“…A primary reliance on carrier frequency has been questioned based on the notion that any threshold is arbitrary and will inevitably result in missing the identification of carriers of very rare conditions. 34 We agree with this concern, but maintain that widespread acceptance of ECS and access to it in the United States necessitate an incremental increase in the panel size rather than an increase to many hundreds of conditions.…”

Section: Carrier Frequencymentioning

confidence: 79%

Expanded carrier screening: What conditions should we screen for?

2023

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Carrier screening tests reproductive couples for their risk of having children affected by serious monogenic conditions. Carrier screening has historically been offered for certain conditions in high‐risk populations. However, more recent evidence has shown that offering carrier screening to all patients, regardless of their ethnicity, more effectively and equitably identifies at‐risk couples. Coupled with technology that enables screening for a nearly unlimited number of conditions, this expanded carrier screening (ECS) approach is now supported by professional society guidelines. Despite recent recommendations by the American College of Medical Genetics and Genomics to screen all patients who are pregnant or considering pregnancy for 113 conditions, questions remain about what conditions should be included on a core ECS panel. Here, we briefly review the history of carrier screening and guidelines on criteria for panel design. We then suggest which of these criteria are most critical, as well as thresholds to identify which conditions meet these criteria. Based on these interpretations, we recommend a core panel of 64 conditions that would identify the vast majority of at‐risk couples. Widespread adoption of a core panel such as this would result in a marked improvement in the number of patients currently receiving comprehensive carrier screening.

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Section: Carrier Frequencymentioning

confidence: 79%

Expanded carrier screening: What conditions should we screen for?

2023

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“…Furthermore, the Mackenzie's Mission research team recently published a critique regarding the carrier frequency cut‐off recommended by the ACMG, stating that the carrier frequency thresholds were not strongly evidence‐based 29 . The critique proposed that the gene list selected for carrier screening should be dynamic and subject to ongoing evaluation and updates based on emerging evidence 29 . In addition to this criticism of the carrier frequency cut‐offs, the issue of reporting variants of uncertain significance (VUS) was raised in this critique 29 .…”

Section: Discussionmentioning

confidence: 99%

“…30 The ACMG recommended that reporting VUS should be considered and discussed in the context of carrier screening panels. 23 However, the Mackenzie's Mission research team opposed this recommendation stating potential concerns such as the uncertain clinical validity, 29,31 as well as unnecessary resource use 29 and distress for individuals undergoing carrier screening. 32 Given the complexities involved in categorizing conditions by severity and the ongoing debate surrounding carrier frequency cutoffs, there is currently no consensus on the design of carrier screening panels.…”

mentioning

confidence: 99%

An overview of reproductive carrier screening panels for autosomal recessive and/or X‐linked conditions: How much do we know?

Wang,

Scuffham,

Byrnes

et al. 2023

Prenatal Diagnosis

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Background & AimReproductive carrier screening seeks to identify couples at a high risk of having offspring affected by autosomal recessive and X‐linked (XL) conditions. The aim of this paper is to provide a comprehensive overview of existing carrier screening panels by examining their gene content and characteristics, identifying the most common genes/conditions included in these panels, and analyzing their listed prices.MethodsA comprehensive evaluation of existing carrier screening panels was conducted by searching for web‐based content, reviewing information brochures, and establishing direct contact with the providers via email or phone.ResultsTwenty‐two panels and their providers were identified with a cumulative total of 2205 unique genes. The number of genes included in these panels varied from 44 to 2054. Only 15 genes (0.7%) were included in all the panels. The carrier frequency of these 15 common genes and their associated conditions varied greatly, but the conditions associated with the genes are “severe”. The price of these 22 panels ranged from $349 to $4320 per couple (USD in 2023). The correlation between the listed price and the number of selected genes among these panels was small and not statistically significant (r = 0.1023, p = 0.6959).ConclusionConsiderable discrepancies exist among carrier screening panels. Ongoing research and monitoring are necessary to capture the dynamic nature of the carrier screening landscape, providing up‐to‐date information for clinical practice and informed decision‐making.

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“…However, screening of individuals was considered problematic in some studies as genetic counselling for individual carrier status places a huge burden on genetic counselling resources and will not always be relevant to reproductive decision-making [ 27 ]. As evidenced by Bell et al [ 61 ], where a screening panel of 437 genes identified 70% of participants as carriers, the sheer volume of genetic counselling required for individual carrier status as a result of RGCS at scale will outstrip the genetic counsellor resources available [ 13 , 19 , 30 ]. Similarly challenging is when genetic carriers are identified via sequential screening offered in early pregnancy but the partner is not available for screening or refuses screening.…”

Section: Discussionmentioning

confidence: 99%

“…In 2021 the American College of Medical Genetics (ACMG) [ 13 ] released practice guidelines relating to RGCS and highlighted that traditional genetic counselling methods can be longwinded and likely lack feasibility at the population scale. Despite the ever-increasing number of accredited genetic counsellor training courses and graduates entering the workforce, there are simply not enough genetic counsellors to meet the demand for pre- and post-test counselling for RGCS at the population scale [ 13 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Counselling Needs for Reproductive Genetic Carrier Screening: A Scoping Review

Edwards

Laing

2022

JPM

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Reproductive genetic carrier screening provides individuals and couples with information regarding their risk of having a child affected by an autosomal recessive or X-linked recessive genetic condition. This information allows them the opportunity to make reproductive decisions in line with their own beliefs and values. Traditionally, carrier screening has been accessed by family members of affected individuals. In recent years, improvements to accessibility and updates to recommendations suggest that all women planning or in early pregnancy should be offered reproductive genetic carrier screening. As uptake moves towards the population scale, how can the genetic counselling needs of such large-scale screening be met? A scoping review of the literature was performed to ascertain what the genetic counselling needs of reproductive genetic carrier screening are, and what future research is needed. Four broad themes were identified in the existing literature: (1) The offer—when and in what context to offer screening; (2) Information—the importance of and what to include in education, and pre- and post-test counselling; (3) Who and how—who the genetic counselling is performed by and how; (4) Personalization—how do we find the balance between standardized and individualized approaches? Based on the existing literature, we present a set of recommendations for consideration in implementing population-scale reproductive genetic carrier screening as well as suggested areas for future research.

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Correspondence on “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)” by Gregg et al

Cited by 10 publications

References 14 publications

Expanded carrier screening: What conditions should we screen for?

Expanded carrier screening: What conditions should we screen for?

An overview of reproductive carrier screening panels for autosomal recessive and/or X‐linked conditions: How much do we know?

Genetic Counselling Needs for Reproductive Genetic Carrier Screening: A Scoping Review

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