Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices.

Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as "healthy heterozygotes" or "unaffected carriers" should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with "genotype-to-risk." In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.

Legal challenges in reproductive genetics.

Recent advancements in reproductive genetics have resulted in the availability of an extraordinary amount of new and detailed information for patients and providers. Whereas this information can inform many who are facing difficult clinical decisions, it can also introduce complex and uncertain choices. Expanded carrier screening and preimplantation genetic diagnosis for aneuploidy are important examples of new genetic techniques that are now widely used in reproductive medicine. This paper will explore these techniques through a medical-legal prism to better understand the opportunities and obligations incumbent on both patients and providers in this new age of genetic diagnosis.

Growing complexity of (expanded) carrier screening: Direct-to-consumer, physician-mediated, and clinic-based offers.

Since the introduction of out-of-hospital health-related genetic tests more than a decade ago, the landscape of genetic testing services has grown in complexity. Although initially most genetic tests for health purposes were offered as direct-to-consumer services, that is, without the mediation of a medical professional, currently many commercial providers require that their tests be ordered by a licensed physician. At the same time, some commercially developed health-related genetic tests are gaining support from the professional medical community and are finding their way into clinical practice. Therefore, we differentiated between three types of genetic testing offers: direct-to-consumer, physician-mediated, and clinic-based genetic testing. Expanded carrier screening tests for recessive disorders are currently available through all the three models of genetic testing. Herein, we review the present landscape of expanded carrier screening offers by highlighting the distinct issues associated with each of the three types of genetic testing.