Genetic Disorders and the Fetus. Группа авторов

not to be rushed but characterized by sensitivity and empathy. Informing a couple with bad news about the fetus by telephone or email is unacceptable. Arrangements for a follow‐up visit and support where needed is advisable. Ptacek and Eberhardt⁹⁶⁹ and others,⁹⁷⁰ in reviewing the literature, noted consensus recommendations in breaking bad news that included the aforegoing and sitting close enough for eye contact without physical barriers. Identifying a support person, if the partner cannot/will not attend the consultation, is important and knowledge of available resources is valuable. All of the above points are preferences that have been vocalized by parents receiving bad news during pregnancy or about their infants.⁹⁷¹

      Almost all couples would have reached this juncture through maternal serum screening, noninvasive prenatal testing, an ultrasound or MRI study, or amniocentesis/CVS for maternal age, for established known carriers, because of a previously affected child, being an affected parent, or having a family history of a specified disorder. More recently, prenatal diagnosis using whole‐exome sequencing⁹⁷² has led to the diagnosis of unexpected genetic disorders, and in the process introduced ethical issues and challenging quandaries.^{973, 974} Commonly, an anxious patient insists on a prenatal study. Physicians are advised not to dissuade patients from prenatal diagnosis but rather to inform them about the risks of fetal loss balanced against the risk of fetal abnormality, distinctly different from recommendations for accepted indications. Given the low risks, prenatal diagnosis can be offered to all couples (see Chapter 9).

      Recognition of a fetal abnormality by imaging, molecular, or cytogenetic study may reveal, for the first time, the genetic disorder in an affected asymptomatic parent. Robyr et al.⁹⁷⁵ described 20 such parents with disorders including spinal muscular atrophy, DiGeorge syndrome, osteogenesis imperfecta, arthrogryposis, and Noonan‐like syndrome.

Frequently, second‐trimester ultrasound studies reveal fetal abnormalities of uncertain etiology with a subsequent normal karyotype. A chromosomal microarray may enable a precise diagnosis in 6–8.1 percent^{976, 977} (see Chapter 13). In a legal case, sequential observations noted prominent lateral cerebral ventricles, multiple thoracic hemivertebrae, and intrauterine growth restriction. Amniocyte chromosome studies were normal. The parents were not counseled about the potential for intellectual disability despite no definitive diagnosis. The child was born with holoprosencephaly with marked psychomotor delay. Diagnostic uncertainty must be shared with parents at risk. Uncertainty should not and cannot be suppressed for the patient's sake. Expressing uncertainty does not imply ignorance or incompetence. An honest accounting of the problems at hand, the offer of a second opinion, and an empathetic approach all go a long way in averting a catastrophic outcome and aggravating litigation. Moreover, responsibility shared is anxiety halved.

      Decision making

      The presence of both parents for the consultation concerning possible elective abortion for a fetal anomaly is critical in this situation. All the principles governing the delivery of genetic counseling and discussed earlier apply when parents need to decide whether or not to continue their pregnancy. A brief explanation of some of the key issues follows, culled from over 50 years of experience in this very subject.

      Doubt and disbelief crowd the parental senses in the face of such overwhelming anxiety. Was there a sample mix up? How accurate is this diagnosis? How competent is the laboratory? Have they made errors in the past? How can we be certain that there has been no communication failure? Is there another couple with the same name? There are endless questions and endless doubts. Each and every one needs to be addressed carefully, slowly and deliberately, with painstaking care to provide the necessary assurance and reassurance. Needless to say, the clinical geneticist or counselor must have thoroughly checked all the logistics and potential pitfalls before initiating this consultation. Errors have indeed occurred in the past.^{184, 185}

      The central portion of the communication will focus on the nature of the defect and the physician or counselor providing the counseling should be fully informed about the disorder, its anticipated burden, the associated prognosis, life expectancy, and the possible need for lifetime care. A clear understanding of the potential for pain and suffering is necessary, and an exploration concerning the effect on both parents and their other children is second only to a discussion about the potential effects on the child who is born with the condition in question. Any uncertainties related to diagnosis, prognosis, pleiotropism, or heterogeneity should emerge promptly. Questions related to possible future pregnancies should be discussed, together with recurrence risks and options for prenatal diagnosis.

      The question concerning a repeat prenatal study is invariable, at least if not stated then certainly in the mind of the parents. There are occasions when a repeat test might be appropriate, especially if there is a failure to reconcile cytogenetic or molecular results with expected high‐resolution ultrasound observations. Maternal cell contamination (see Chapters 9, 11, and 14), while extremely unlikely in almost all circumstances, requires exclusion in some others. Some prenatal diagnoses may not easily be interpretable and a phenotype may not be predictable with certainty. A de novo supernumerary chromosome fragment in the prenatal cytogenetic analysis (see Chapter 11) or a microdeletion or microduplication (see Chapter 13) are key examples. VOUS, especially in a gene known to harbor pathogenic mutations, is unnerving. Where a VOUS is uninterpretable, decision making reverts to the fetal anomaly seen or biochemical abnormality observed. The sensitive counselor should offer a second opinion to anxious parents facing an uncertain prenatal diagnosis. The “compleat physician” anticipates virtually all of the patient's questions, answers them before they are asked, and raises all the issues without waiting for either parent to vocalize them.

      Occasionally, there are powerful disparate attitudes to abortion between the spouses as discussed earlier. Such differences would best be considered during the preconception period, rather than for the first time when faced with a serious fetal defect. Resolution of this conflict is not the province of the physician or counselor, nor should either become arbitrator in this highly charged and very personal dispute, in which religious belief and matters of conscience may collide. The physician's or counselor's duty is to ensure that all facts are known and understood and that the pros and cons of various possible scenarios are identified in an impartial manner. A return appointment within days should be arranged. Questions of paternity have also suddenly emerged in this crisis period and can then be settled, sometimes with painful certainty.

Elective abortion: decision and sequel

      Among the greatest challenges clinical geneticists and genetic counselors face is the consultation in which the results of prenatal studies indicating a serious fetal defect are communicated to parents for the first time. These appointments must not be rushed. It is important that the many variables influencing parental decisions about pregnancy termination be recognized.^{978, 979} The quintessential qualities a counselor will need include maturity, experience, warmth and empathy, sensitivity, knowledge, communication skill, and insight into the psychology of human relationships, pregnancy, and grieving. Personal experience with loss or bereavement is likely to influence the emotional guidance provided.⁹⁸⁰ Certainly there is a wealth of literature suggesting inadequate preparation for those who ultimately care for individuals facing bereavement or death.^{980, 981} An in‐depth understanding of the disability that the affected child and parents could anticipate is of obvious importance. The principles and prerequisites for counseling discussed earlier apply fully in these circumstances and the fact that this is a parental decision, not a medical “recommendation,” should not need reiteration.

      Anticipatory counseling in