**1.1. Prenatal genetic counseling—when and how**

Congenital anomalies can be caused by *chromosome abnormalities, single-gene defects, multifactorial inheritance*, or *epigenetic or nongenetic factors*. It is notable that in up to 50% of all cases no apparent identifiable cause can be found. Any microscopically detectable autosomal imbalance, such as trisomy, duplication, deletion, or monosomy, will result in severe structural and developmental abnormality, most of which are lethal conditions. Single-gene defects have been associated with congenital abnormalities that might involve one or more organs and systems with or without an obvious underlying embryological relationship. Multifactorial inheritance accounts for the majority of congenital abnormalities, including isolated malformations, in which genetic factors can clearly be

It should be noted that although malformations are always thought to be congenital, not all congenital abnormalities are "literally" malformations. Anomalies due to an intrinsic, genetic (chromosomal aberration and gene mutation), or multifactorial factor represent approximately 45% of all congenital abnormalities. These are considered primary congenital malformations. Anomalies resulting from the action of an extrinsic factor—chemical, physical, biological agents, and possibly maternal condition—add up 5% of the congenital anomalies identified and are considered secondary congenital anomalies. For the remaining 50% of these abnormalities, the cause is unknown and therefore cannot be included in this classification [1].

The impact of genetic variability on embryogenesis and fetus development established medical genetics as essential for the prevention of congenital anomalies, early detection, and appropriate management. In the past, when dealing with congenital malformations, medical professionals had to face two major issues: a late detection of the anomaly and the lack of an identifiable cause. The act of disease prevention back then was virtually

Though, in the last decade of rapidly progressing genomic technologies, genetic diagnosis tools became widely accessible, playing an important role in both clinical practice and research. The completion of the Human Genome Project has contributed greatly to our under-

The importance of determining the genetic cause of birth defects lies in the need for appropriate case management and genetic counseling. Genetic counseling is meant to assist parents in making informed decisions. Through counseling, parents learn about the risk of having a newborn with a congenital malformation and the nature of the disorder and its natural history, are advised on available testing for that particular case, and discuss options for risk

All attempts must be made to arrive at as precise a diagnosis as possible by evaluating gestational history for environmental factors, family history for genetic factors, and patient anatomy for clues to embryologic etiopathogenic mechanisms. Evaluating family history for genetic factors, gestational history for environmental factors, and patient phenotype for information on embryologic mechanisms is mandatory to arrive at as precise a diagnosis as possible.

standing of the molecular basis of genetic disorders.

management and family planning.

involved.

442 Congenital Anomalies - From the Embryo to the Neonate

impossible.

Genetic counseling is a complex medical act, which aims to help families, individuals, and couples to better understand the familial, medical, psychological, and reproductive consequences of the genetic contribution to specific health conditions. It can be offered both preand postnatally.

Fortunately, most babies are born healthy. However, in some pregnancies, a risk for birth defects or other genetic problems may be identified. Geneticists and genetic counselors provide prenatal genetic counseling services for individuals, couples, or families with a concern about the health of their unborn baby.

Prenatal counselling manages cases with risks by understanding prenatal screening and testing options. Increased chance of having a child with a birth defect or genetic condition makes the genetic consultations a necessity. The purpose of genetic counseling is to allow informed decision-making by communicating accurate and complete information and presenting objective diagnostic and therapeutic options [2]. To achieve its goal, information transfer must be made in a clear but neutral way, using simple language, respecting ethical and cultural values.

*Pretest counseling.* At this stage, the couple will be informed on the objectives of the counseling session regarding the suspicion of congenital anomaly for the pregnancy.

The genetic counselor/geneticist will lay down the alternatives the couple has for following up the pregnancy and explain the possibility and alternatives for testing for identifying the cause of the congenital anomalies identified. The geneticist must take into consideration that accepting to be tested may be influenced by psychosocial factors, such as ethnicity, sociodemographic status, and the presence of the partner during the counseling session [3].

If the couple expresses the desire for prenatal diagnosis, the counselor must present the objectives, benefits, risks, limitations, costs, and alternatives for each of the available screening and/ or diagnosis techniques. The patient has the right to accept or refuse a given recommendation. At all times, it must be clear that testing is optional.

The counseling must go beyond making an informed choice for testing and what this step entails, but also preparing the couple for possible outcomes dictated by a positive or negative result.

*Posttest counseling.* Posttest counseling must explain thoroughly the significance of the result, the meaning of a positive or negative result, and go over the limitations of each test. It must also suggest other possible confirmatory or complementary tests or alternatives [2] and unconditionally support the patient's options, respecting the autonomy of his/her choice.

One of the most encumbering tasks of genetic counseling is presenting a family with the fact that their child has a genetic condition or birth defect. Most of the test results face the couple with a termination/no-termination decision.

As part of the informed decision-making process, the couple must be informed in detail on the clinical presentation and prognosis of the disorder identified. This is often problematic in chromosomal disorders: (1) genotypic variability—the phenotype will vary depending on the extent of the genetic defect and (2) phenotypic variability—the evolution of a case can vary greatly, even between carriers of the same type of anomaly.
