Genetic Disorders and the Fetus. Группа авторов

the critical imperative that the concept of genetic counseling be introduced in high school and in continuing public education^335–339 about genetic disease. Children sensitized in school about the importance of the family history, elements of heredity, concepts of individual susceptibility and risk, and opportunities for anticipatory prevention of unnecessary catastrophes are likely to better comprehend pregnancy risks and options.

      Genetic counseling and prenatal diagnostic services are of little avail if many women attend for their first antenatal visit after 16 weeks of gestation. Currently, this is the case in many urban hospitals in the Western world, where between 20 and 40 percent of obstetric patients arrive at this late stage. Education beginning in high school and continued by public health authorities could effectively communicate the critical importance of preconception and prenatal care.

      Duty to recontact

The enormous expansion of genetic testing, including expanded carrier testing, chromosomal microarrays, whole‐exome sequencing, and whole‐genome analysis, has further emphasized the continuing responsibility of communicating results. That obligation extends well after a clinical visit, given that the information may inform a patient's risks or affect reproductive decisions.^{336, 337}

      Mersch et al.³⁴⁰ reported that among 1.45 million people who received genetic testing for hereditary cancer risks between 2006 and 2016, further communications were necessary since 6.4 percent had unique variants reclassified. Some 7.7 percent of VOUS were reclassified and 8.7 percent were upgraded. As an aside, following genetic research and new meaningful results, an ethical duty to inform the patient has become apparent.³⁴¹

      In a study by Carrieri et al. most patients viewed recontact as desirable.³⁴² However, a range of barriers to implementation have been raised, including a lack of resources, potential negative psychological consequences, unclear operational definitions of contacting, policies that prevent healthcare professionals from recontacting, difficulties locating patients, intrusion into privacy, and a violation of a patient's interests and right not to know.^343–346

      To obviate any concern that failure to recontact could be construed as negligence,³⁴⁶ patients need to be told as part of the informed consent for testing of their responsibility to be in contact, either annually or when childbearing is planned or in progress or if a relevant change has occurred in their family history. This is especially the case when sequencing or a chromosomal microarray reveals a VOUS. We have for decades appended a statement in our postgenetic counseling letter to the referring physician and the patient alike about the need to remain in contact. There is indeed a duty to recontact, but that duty is reciprocal, despite the objections of some.³⁴⁷

      Medical genetics consultations frequently involve only one encounter and the requirement to contact that patient years later may be regarded as both irrational and unreasonable. Pelias pointed to a 1971 lawsuit³⁴⁸ in which the University of Chicago failed to notify women who had been given diethylstilbestrol. The university had apparently become aware of the dangers of this drug but had delayed notification for 4–5 years. In yet another case, after a single visit to her gynecologist for insertion of an intrauterine device (a Dalkon shield), a woman sued this physician for failing to notify her of the subsequently recognized risks of this device.³⁴⁹ In that case, as Pelias noted, the court allowed the case to proceed because of the continuing status of the physician–patient relationship and because the physician had a “separate duty to act.”³⁵⁰ Clearly, recommendations for recontact should be recorded in clinical notes and echoed in letters to referring physicians and patients alike. Initial ACMG guidelines regarding recontacting³⁵¹ were revised in 2008³⁵² and framed as “points to consider” in 2018.³⁵³ These were the points:

      1 Recontact is fundamentally a shared responsibility among the ordering healthcare provider, the clinical testing laboratory, and the patient.

      2 As part of the informed consent process, the patient or family should be advised that:Changes in interpretation of clinical genomic test results are possible and recontact may be important for patient care.If the patient's medical history or family history changes, the patient should make the healthcare provider aware.Important times for the patient to request an update are at life cycle junctures such as preconception planning, pregnancy, and changes in family history information, including sudden unexpected death or the diagnosis of a major health issue in the person originally tested or a close relative.When seeking an updated variant interpretation, the patient or family should contact the provider who ordered the test, the clinical geneticist who interpreted the test result with the patient, and/or the clinical testing laboratory for an update on a result with an uncertain interpretation. Alternatively, the patient can request their primary care or specialty provider to contact a genetics provider.The patient or family has a right to decline recontact.The patient or family should register with the healthcare facility patient portal if available.It is the patient's obligation to provide updated contact information over time.

      3 The ordering provider should emphasize, through discussion and in written explanation to the patient, that the ordering provider cannot promise that recontact regarding a revised interpretation will occur unless the patient initiates the recontact.

      4 The discussion regarding recontact should be documented in the medical record. The patient or family ideally will be given a copy of the recontact policy.

      5 The ordering provider should inform the patient of the specific tests performed and which laboratory performed the analysis, typically by providing a copy of the test report. The patient should be encouraged to keep the report with their important health information. The test report should be entered into the electronic health record (EHR) and should be provided to the referring physician.

      6 The responsibility to inform the ordering physician of variant reclassification or discovery of a new gene–disease relationship rests with the clinical laboratory.

      7 Medical geneticists need to inform referring providers that, even if the patient is referred to a medical geneticist for counseling regarding test results, the ordering physician will remain the primary contact for the laboratory.

      8 If contacted by the laboratory with an updated result, the ordering physician should make reasonable efforts to recontact the patient.

      Do no harm

      The classic exhortation primum non nocere (first, do no harm) is as pertinent to clinical genetics as it is to medicine in all specialties. Attention to this principle arises particularly in the context of predictive genetic diagnosis, possible for a rapidly escalating number of neurodegenerative disorders (e.g. Huntington disease, frontotemporal dementia, Machado–Joseph disease), cardiovascular and other serious disorders including multiple endocrine neoplasia type 2B, and breast, colon, and other malignancies. Published recommendations and guidelines³⁵⁴ urge rigorous pretest and post‐test genetic counseling. Many factors impact the attempt at risk communication and prediction. Patients who attend for genetic counseling invariably have their own, possibly tentative idea, about their personal risks. Their perception of risks will vary according to their family history, educational level, socioeconomic status, psychological state of mind, life experience, gender, health status, language ability, culture, IQ, and comprehension of mathematics.^355–359 Those who initially thought their personal risks or risks of having an affected child were 50 percent and are informed that the risk only approximates 10 percent may be relieved and not even opt for any testing. Others may be startled to hear that all couples face a 3–4 percent risk on average for bearing a child with a birth defect, intellectual disability, or genetic disorder.

      The inherent harm that could potentially be done by predictive testing is the potential for demoralization and depression with possible suicidal consequences (see later discussion). Extreme caution is recommended in considering predictive testing for a disorder without curative, let alone meaningful, palliative treatment. Although for certain dominant disorders some 50 percent of individuals at risk may receive good news, the other 50 percent face, effectively, a death sentence.