{"id":2218,"date":"2026-09-21T18:06:53","date_gmt":"2026-09-21T15:06:53","guid":{"rendered":"https:\/\/gynaikologos-komotini.gr\/?p=2218"},"modified":"2026-09-22T18:35:59","modified_gmt":"2026-09-22T15:35:59","slug":"expanded-carrier-screening-ecs-from-fetal-genetic-risk-to-maternal-health","status":"publish","type":"post","link":"https:\/\/gynaikologos-komotini.gr\/en\/expanded-carrier-screening-ecs-from-fetal-genetic-risk-to-maternal-health\/","title":{"rendered":"Expanded Carrier Screening (ECS): From Fetal Genetic Risk to Maternal Health"},"content":{"rendered":"\t\t
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\u00a0<\/p>

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The traditional aim of carrier screening<\/strong> was relatively straightforward: to identify two unaffected carriers of the same autosomal recessive disorder, or a woman carrying an X-linked disorder, and to estimate the genetic risk for their offspring. With the development of next-generation sequencing (NGS)<\/strong>, however, hundreds of genes can now be analyzed simultaneously, transforming Expanded Carrier Screening (ECS) from targeted testing into a broader strategy for reproductive prevention and planning.\"\"<\/p>

Epidemiologically, approximately 0.3% of couples are at risk of having a child affected by cystic fibrosis, spinal muscular atrophy, or Fragile X syndrome. Furthermore, more than 3,000 genes have been associated with genetic disorders involving either the autosomal chromosomes (22 pairs) or the sex chromosomes (X\/Y).<\/p>

The overall significance is greater than individual rare disorders might suggest. Approximately 1\u20132% of couples<\/strong> may be at increased risk of having a child affected by a selected severe recessive disorder. Studies of children diagnosed with autosomal recessive or X-linked disorders have suggested that a proportion of these conditions could potentially have been anticipated through expanded carrier screening.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t

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ECS may therefore be considered broadly rather than exclusively on the basis of ethnic or ancestral background, as traditionally occurs with conditions such as \u03b2-thalassemia. It is particularly relevant for consanguineous couples, couples experiencing infertility, and those undergoing assisted reproduction<\/strong>. Whenever possible, screening before conception is preferable because it provides a wider range of reproductive options: natural conception followed by prenatal diagnosis, IVF with preimplantation genetic testing for monogenic disorders (PGT-M<\/strong>), the use of donor gametes, or acceptance of the identified genetic risk. Major professional guidance also emphasizes the advantages of preconception carrier screening and counseling.<\/p>

However, identifying a carrier does not always concern only the health of a future child. It may also have direct implications for the mother’s own health.<\/strong><\/p>

The traditional assumption that heterozygous carriers are invariably asymptomatic does not apply to every gene. In a large study, approximately 9% of individuals<\/strong> undergoing expanded carrier screening carried variants associated with potential clinical implications for themselves.<\/p>

Of particular importance to obstetricians, approximately 1 in 40 women<\/strong> may carry a genetic condition that could influence her medical management during pregnancy.\u00a0<\/p>

The clinical implications can be significant. Women carrying pathogenic variants associated with dystrophinopathies (DMD)<\/strong> may develop or experience worsening dilated cardiomyopathy during pregnancy. Factor V Leiden<\/strong> increases thromboembolic risk, while carriers of pathogenic variants in F11, F8, and F9<\/strong> may have an increased risk of bleeding during delivery.<\/p>

Carriers of ABCB11\/ABCB4<\/strong> variants have an increased risk of intrahepatic cholestasis of pregnancy, whereas female OTC carriers<\/strong> may develop severe hyperammonemic crises during the peripartum period.\"\"<\/p>

A particularly important association involves HADHA\/HADHB<\/strong> and HELLP syndrome or acute fatty liver of pregnancy (AFLP). When the fetus is affected by mitochondrial trifunctional protein deficiency, the reported maternal risk of HELLP\/AFLP may reach 15\u201362%<\/strong>, potentially requiring specialized biochemical surveillance and maternal\u2013fetal medicine monitoring.<\/p>

Some findings also have long-term implications for women’s health<\/strong>, independently of pregnancy. A characteristic example is the FMR1 premutation<\/strong>, which is associated with an approximately 20\u201330% risk of Fragile X-associated primary ovarian insufficiency and may therefore influence reproductive planning and discussions regarding fertility preservation.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t

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ECS can consequently have a threefold clinical role<\/strong>:<\/p>

identification of genetic risk to the fetus \u2192 provision of preconception\/prenatal reproductive options \u2192 identification of potential health risks to the mother herself.<\/strong><\/p>

Nevertheless, indiscriminately expanding screening panels does not necessarily represent progress. Available panels differ substantially in the number and selection of genes included, with only a small number of genes being shared across all panels evaluated in comparative studies.<\/p>

The objective should therefore not be \u201cthe more genes, the better,\u201d<\/strong> but rather the selection of a clinically meaningful panel focusing on serious and potentially actionable disorders, together with appropriate interpretation of pathogenic and likely pathogenic variants<\/strong> and careful management of variants of uncertain significance (VUS)<\/strong>. Furthermore, because manifestations in carriers may depend on the specific variant, interpretation should not be based solely on the name of the gene; the individual variant and the evidence associated with it must also be evaluated.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t

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Clinical conclusion<\/strong><\/span><\/h1>

Genetic counseling should explain the risk of an affected child when both partners carry pathogenic variants associated with the same autosomal recessive condition\u2014typically 25% in each pregnancy<\/strong>\u2014and the inheritance risks associated with X-linked conditions, which depend on the specific disorder, fetal sex, and parental carrier status. Families should also understand that some genetic disorders arise from de novo variants<\/strong> and therefore cannot be predicted through parental carrier screening alone.<\/p>

In contemporary prenatal care, Expanded Carrier Screening should no longer be regarded simply as a test to determine whether a child is at risk of a recessive disorder<\/strong>. It is a tool of preconception and prenatal medicine that can simultaneously define fetal genetic risk, inform a couple’s reproductive options and, in a clinically relevant proportion of women, modify the monitoring and management of the mother herself<\/strong>.<\/p>

The optimal approach is therefore ECS preferably before conception, appropriate testing of both partners, careful panel selection, genetic counseling before and after testing, and individualized obstetric surveillance whenever carrier status has potential maternal clinical implications<\/strong>.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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