Genetic Disorders and the Fetus. Группа авторов

The Florida Supreme Court held that a reasonably prudent physician had a legal duty to warn of a genetically transferable disease.

      The case Safer v. Estate of Pack³⁸⁵ followed a similar theme. The father of Donna Safer was diagnosed in 1956 and surgically treated for colon cancer associated with multiple polyposis. Despite a total colectomy, he died when Donna was only 10 years of age. Subsequently, at the age of 36 years, she was diagnosed with metastatic colon cancer due to autosomal dominant multiple polyposis. She sued her father's surgeon's estate (he died in 1969) for not warning him of the genetic nature and transmissibility of that cancer. The Appellate Court in New Jersey decided that a physician had a duty to warn those known to be at risk of a genetic disorder and went on to state that duty may not always be satisfied by warning the patient.³⁸⁶ About 5 years later, in 2001, the New Jersey Legislature enacted a broad genetic privacy law³⁸⁷ that without consent a physician is prohibited from disclosure of genetic information.^{386, 388}

      A failure to make a diagnosis of the fragile X syndrome in the symptomatic daughter of Kimberly Molloy was followed by her giving birth to a son with this disorder. She sued the three physicians who treated her daughter (Molloy v. Meier).³⁸⁹ The Minnesota Supreme Court (2004) concluded that physicians owed a duty to a third party and that legal action was permissible for the failure to warn.³⁸⁹

      More recently, and in the United Kingdom, the duty to warn came into sharp focus. A man with Huntington disease expressly forbade his doctor from informing his daughter of his diagnosis. She subsequently (and accidentally) learned of the diagnosis when she was already pregnant. She sued her father's physicians (ABC v. St. Georges Healthcare NHS Trust)³⁹⁰ for failure to inform her, claiming she would have terminated her pregnancy. The High Court denied the claim, holding that there was no duty of care. However, the Court of Appeal (2017) overturned this decision, indicating that clinicians may owe a duty to warn a patient's relatives.³⁹¹

      The aforegoing cases, including the decision by the UK Court of Appeal, made it clear that confidentiality in genetics is not absolute^{324, 392, 393} with some exceptions.

Following the ruling of the Court of Appeal, the case returned to the High Court for trial, where the decision was against the claimant (ABC).³⁹¹ Notwithstanding that ruling the Court “introduced a novel legal duty of care owed by doctors to third parties in certain circumstances.”³⁹¹

      Earlier, the UK General Medical Council regarded the transfer of genetic information as justified if failure to do so exposes others to a risk of death or serious harm.^{324, 394} The Joint Committee on Genomics in Medicine concurred³⁹³ and advised that if a breach of confidentiality is to be made, consent for disclosure should be sought, discussion should be held with professional colleagues (e.g. ethics committee), and disclosure should be kept to a minimum, and all actions documented.³⁹⁵ Internationally, many authors have opined and wrestled with these issues and mostly saw the necessity of communicating with relatives of the proband.^396–400

Preconception genetic counseling

      It is an anachronism that preconception genetic counseling in the 21st century, despite being recognized as important, is not widely practiced.^{401, 402} Expectations at the first preconception visit include routine documentation of the medical, obstetric, and family history, the latter regarded arguably as the most important “genetic test.”⁴⁰³ It is now possible to prenatally diagnose all monogenic disorders in which the culprit gene is known. Since 6,739 have phenotypes thus far with recognized single genes,² it is very important for the physician to obtain and record the exact name of the genetic disorder(s) in the family. A history of “muscular dystrophy,” given numerous types, would, for example, not be useful. Patients need a brief explanation as to why they need to obtain the precise information, and the physician's request documented. Review of medical records, photographs (e.g. previous stillbirths), and pertinent autopsy reports, radiographs, brain scans, and chromosome or other special laboratory reports may be necessary, as well as referral for genetic counseling. Physical examination and necessary special tests also focus on acquired and genetic disorders that could, during pregnancy, threaten maternal and/or fetal welfare.

      Previously undiagnosed/undetected disorders may be determined for the first time at this visit and may be important for planned childbearing and the selection of future prenatal diagnostic tests. There is a need to insist that the male partner attend the preconception visit (or absolutely the first prenatal visit), providing an opportunity to detect at least obvious genetic disorders and solidify information possibly provided earlier about his family history. The senior author recalls, over many years during prenatal diagnosis counseling for other issues, diagnosing various disorders in male partners who were wholly unaware of their conditions, including osteogenesis imperfecta, Treacher–Collins syndrome, tuberous sclerosis, neurofibromatosis, Charcot–Marie–Tooth (type 1A) disease, limb girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, blepharophimosis, mitral valve prolapse, the XYY male, and spinocerebellar ataxia.

      The first preconception visit also serves to instruct about the need for folic acid supplementation for the 70 percent avoidance of NTDs (see Chapter 10) and about diabetic control, management of obesity, cessation of illicit drugs, medications, smoking and alcohol. Referral to other specialists (e.g. neurologists), for tailoring medication requirements to safer and possibly less teratogenic agents (e.g. epilepsy, acne), is also recommended. This is also the time for specialists caring for the same patient to confer about the planned care of their patient through pregnancy and for documentation of that interaction to be made.

      Indications for preconception genetic counseling

      The indications for preconception genetic counseling should be determined at the first visit and can be considered in a few clear categories.

      Advanced maternal age

An arbitrary age of 35 years has previously functioned in the United States as an expected standard of care, which requires that a prospective mother be informed of her increased risks of having a child with a chromosome defect, informed of the recommendation for prenatal diagnosis, and given an explanation of the risks of CVS or amniocentesis, with the associated details related to any problems, pitfalls or reservations. Now, given the very low procedural risks, all women should be offered routine prenatal genetic studies that focus on chromosomal analysis and α‐fetoprotein (see Chapter 17). Advances in fetal imaging and low risks of fetal loss following amniocentesis (0.1–0.4 percent) or CVS (0.2–0.4 percent)^{404, 405} (see Chapter 9) have led to the policy change. The advent of noninvasive prenatal testing (see Chapters 6 and 7) has further decreased the need for CVS or amniocentesis.

      Excluding infants with chromosome abnormalities, a prospective analysis of 102,728 pregnancies (including abortions, stillbirths, and livebirths) in Texas found that the incidence of congenital malformations increased significantly and progressively in women after 25 years of age.⁴⁰⁶ The authors found that an additional age‐related risk of nonchromosome malformations was approximately 1 percent in women 35 years of age or older. The odds ratio for cardiac defects was 3.95 in infants of women 40 years of age or older when compared with women aged 20–24 years.

      Pregnancy outcomes related to maternal age were reported in a Danish study of 369,516 singleton cases.⁴⁰⁷ Pregnancies were followed from 11–14 weeks to delivery or termination and the age groups (20–34, 35–39, and ≥40 years) compared. Adverse outcomes included chromosomal abnormalities, congenital malformations, miscarriage, stillbirth, and delivery