Prenatal genetic carrier screening in the genomic age.

The Society for Maternal-Fetal Medicine, American College of Obstetricians and Gynecologists (ACOG), and American College of Medical Genetics and Genomics (ACMG) held a workshop entitled "Prenatal Genetic Testing" on January 25, 2017 to address several questions arising from the increasing implementation of preconception and prenatal expanded carrier screening (ECS). ECS allows for identification of a greater number of genetic sequencing changes (not all of which cause disease) and simultaneous testing for an increased number of genetic conditions without limitation to specific ethnic groups. The workshop participants reached consensus on the following: ethnicity based testing cannot be completely abandoned in favor of panethnic ECS; the specific approach to screening should be a patient's choice and not driven solely by provider preference; organizations should work to develop a framework for vetting conditions that should be reported on ECS panels; compared with prenatal screening, preconception screening is ideal and, at this time, due to the costs and the need for timeliness associated with prenatal screening posttest counseling and testing, that when ECS is offered it should be presented as a preconception option; preconception and prenatal panels should be identical across the spectrum of patients, including those undergoing assisted reproduction; adult-onset conditions should not be included on ECS panels; partners should be offered next-generation sequencing to identify rare variants when the first partner screened is determined to be a carrier; re-screening in subsequent pregnancies is not indicated, despite the potential for expansion of carrier screening conditions and variants; and more education about ECS for providers and patients is necessary to implement prenatal carrier screening in a responsible way.

Prenatal detection of 10q22q23 duplications: dilemmas in phenotype prediction.

OBJECTIVES: The phenotype for 10q22q23 duplication is diverse, ranging from intellectual disability and dysmorphism to normal development. Interpreting the clinical significance of the duplication identified in this region is difficult, especially in the prenatal setting. This study aimed to characterize the prenatal findings associated with this submicroscopic imbalance and discuss the dilemmas in predicting the phenotype of 10q22q23 duplications. METHODS: This is a retrospective study of three cases of 10q22q23 duplications diagnosed prenatally by chromosomal microarray analysis. Detailed pregnancy outcome and pediatric follow-up were documented. RESULTS: The genotypic and phenotypic features of the reported cases were discussed. 10q22q23 duplications are associated with an unpredictable and variable phenotypic outcome. Despite there was no phenotype found to be shared by 50% of the duplication cases, congenital heart defects, hypotelorism, and developmental delays including speech and motor delay seem to be more common. CONCLUSIONS: The phenotype of 10q22q23 duplication is highly variable prenatally and postnatally. Identification of additional affected individuals with similar duplications is needed to provide further insights into the pathogenesis of this microduplication. © 2016 John Wiley & Sons, Ltd.

Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.

The transnational alliance for genetic counseling: promoting international communication and collaboration.

The Transnational Alliance for Genetic Counseling seeks to promote communication and collaboration among genetic counselor educators, internationally. Connecting and building global relationships among colleagues also promotes the development of the genetic counseling profession. Genetic counselors everywhere can achieve deeper understanding of their work by seeking international perspectives.

Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995-2011).

OBJECTIVE: The objective of this study was to review the published literature on pregnancy termination following a prenatal diagnosis of Down syndrome in the United States. METHOD: A systematic search of US English-language articles (1995-2011) was conducted to identify primary research studies that reported data for pregnancies with definitive prenatal diagnosis of Down syndrome with subsequent pregnancy termination. Studies that provided indirect estimates of pregnancy termination, such as mathematical models, were excluded. The weighted mean termination rate was calculated across studies. RESULTS: Twenty-four studies were accepted. The weighted mean termination rate was 67% (range: 61%-93%) among seven population-based studies, 85% (range: 60%-90%) among nine hospital-based studies, and 50% (range: 0%-100%) among eight anomaly-based studies. Evidence suggests that termination rates have decreased in recent years. Termination rates also varied with maternal age, gestational age, and maternal race/ethnicity. CONCLUSION: This systematic review presents the largest synthesis of United States data on termination rates following a prenatal diagnosis of Down syndrome. Evidence suggests that termination rates are lower than noted in a previous review that was based on less contemporary studies and had an international focus. Heterogeneity across studies suggests that a summary termination rate may not be applicable to the entire US population.

Contemporary genetic counseling.

Genetic counseling is a specialty service integrally related to obstetrics and gynecology. This article discusses the genetic counseling resources available to the obstetrician gynecologist, including contact with referral centers near their practice and web-based resources for current genetic information. Indications for genetic counseling that incorporate new approaches and technologies are highlighted.

Declaración de consenso sobre el diagnóstico prenatal del síndrome de Down / No disponible

Recientemente se han aireado las preocupaciones mostradas por partede las organizaciones que abogan por la dignidad de las personas con síndrome deDown sobre el cribado y diagnóstico prenatal, particularmente en respuesta a los Boletinessobre Práctica nos. 77 y 88 emitidos por el American College of Obstetritians andGynecologists. El Programa de Consejo Genético de la Universidad de Carolina del Sur(PCG-UCS) decidió que había llegado la hora de convocar a representantes de las organizacionesimplicadas para discutir de forma abierta las percepciones y malentendidossobre las pruebas prenatales en cuanto se relacionan con el síndrome de Down,con el propósito de identificar áreas de consenso sobre las que se pueda seguir elaborando.El documento que acompaña es el resultado de dos días de conversaciones y untestimonio de lo que puede ocurrir cuando el objetivo es explorar un terreno comúnpara conseguir un bien superior(AU)

Lost in transition: challenges in the expanding field of adult genetics.

It is increasingly clear that medical genetics has broad relevance in adult clinical medicine. More adult patients with genetic conditions are being recognized, genetic testing for adult-onset genetic conditions is expanding, and children with genetic conditions are now more likely to survive to adulthood. While the number of patients who could benefit from medical genetic services increases, adult care providers are less well educated about clinical genetics and are not sufficiently prepared to meet the growing needs of this population. Genetics professionals may also be ill-suited for this challenge, since geneticists and genetic counselors have traditionally had greater experience in pediatric and prenatal settings. Communication between primary care physicians who treat adults and the genetics community is currently suboptimal and the identification and subsequent referral of adult patients for genetic services need improvement. Finally, published guidelines that address how to deliver genetic services to adult patients are unavailable for many genetic conditions. In this article we address the challenges of transitioning genetics services from traditional, and largely pediatric-based models to paradigms that can best address the needs of adult patients with genetic conditions. Potential solutions and the practicality of implementation of a team-based approach to adult genetic medicine, including the application of genetic counseling, are also discussed.

Constitutional mosaic trisomy 21 and azoospermia: a case report.

Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure.