**2. Genetic counseling in chromosomal congenital anomalies**

Carrier and aneuploidy screening and diagnostic testing have expanded intensely over the past two decades [2], which is justifiable given the estimate of 5.3% of the neonates affected by a genetic disorder. Despite ultrasound and biochemistry reasons for recommending a prenatal diagnosis, genetic testing in pregnancy is optional. Decisions about undergoing testing should be expressed, consented, and based on individual patient's values and needs and guided by the geneticist during counseling sessions.

Other chromosomal anomalies are structural, such as deletions, duplications, inversions, insertions, translocations, etc. (**Figures 2** and **3**). They are rare and require different diagnosis

Prenatal Genetic Counseling in Congenital Anomalies http://dx.doi.org/10.5772/intechopen.74394 445

Possible alternatives for screening ("Prenatal Biochemical and Ultrasound Markers in Chromosomal Anomalies") and diagnosis ("Genomic Testing for Prenatal Clinical Evaluation of Congenital Anomalies") are presented in detail in different chapters, due to their marked

In the current section, we aim to cover several genetic counseling concepts in a few hypothetical situations of congenital anomaly with underlying chromosomal cause. Pre- and posttesting counseling are a prerequisite of all genetic counseling, but the genetic consult comprises also of a detailed assessment of medical history, psychosocial assessment, and family history,

The possible mechanism by which the chromosomal anomalies occur is usually due to errors in the cell division cycles: nondisjunction in the maternal meiotic division I, and, less fre-

The etiology is mostly unclear, but the probability of chromosomal anomalies increases with maternal age [4], and this is one of the most common etiological factors. Predisposition to

strategies, counseling, and management of the case.

importance in genetic testing and counseling.

**Figure 1.** Karyotype 45,X—monosomy X.

which we are not focusing on here [3, 6, 7].

quently, paternal origin [8] or meiosis II [9].

Congenital anomalies can be caused by chromosomal, monogenic, and multifactorial disorders [4]; out of which, chromosomal anomalies have a significant impact given their combined frequency of 1 in 153 pregnancies [5] and the reserved prognosis for many of them.

Aneuploidies are the most frequent chromosomal anomalies. Aneuploidies are numerical disorders (**Figure 1**)—the number of chromosomes differs to the normal state, called euploidy. Any of the chromosomes, autosomes, or heterosomes can be affected. Aneuploidies can be complete, involving the whole chromosome, or partial. From a single fertilized egg, more populations of cells of different genotypes can develop—this abnormal situation is called mosaicism. Due to their high incidence, three complete trisomies bear significance for the prenatal diagnosis: trisomy 21 (T21—Down syndrome), 18 (T18—Edwards syndrome), and 13 (T13—Patau syndrome).

**Figure 1.** Karyotype 45,X—monosomy X.

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

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

These questions are perhaps among the most frequent during the counseling session and we will try to answer them briefly below. The probability reoccurrence is called "recurrence risk." Recurrence risk assessment and counseling is based on a combination of theoretic risk assessment and empiric data. Families and patients should be informed on the assumptions

This chapter is focused on genetic counseling in congenital anomalies, caused by chromosomal, monogenic, or plurifactorial anomalies, as well as on preimplantation genetic diagnosis.

Carrier and aneuploidy screening and diagnostic testing have expanded intensely over the past two decades [2], which is justifiable given the estimate of 5.3% of the neonates affected by a genetic disorder. Despite ultrasound and biochemistry reasons for recommending a prenatal diagnosis, genetic testing in pregnancy is optional. Decisions about undergoing testing should be expressed, consented, and based on individual patient's values and needs and

Congenital anomalies can be caused by chromosomal, monogenic, and multifactorial disorders [4]; out of which, chromosomal anomalies have a significant impact given their combined frequency of 1 in 153 pregnancies [5] and the reserved prognosis for many of them.

Aneuploidies are the most frequent chromosomal anomalies. Aneuploidies are numerical disorders (**Figure 1**)—the number of chromosomes differs to the normal state, called euploidy. Any of the chromosomes, autosomes, or heterosomes can be affected. Aneuploidies can be complete, involving the whole chromosome, or partial. From a single fertilized egg, more populations of cells of different genotypes can develop—this abnormal situation is called mosaicism. Due to their high incidence, three complete trisomies bear significance for the prenatal diagnosis: trisomy 21 (T21—Down syndrome), 18 (T18—Edwards syndrome), and

with a termination/no-termination decision.

444 Congenital Anomalies - From the Embryo to the Neonate

involved and the limitations of such estimates.

guided by the geneticist during counseling sessions.

13 (T13—Patau syndrome).

greatly, even between carriers of the same type of anomaly.

**1.2. "Why did it happen? Will it happen again? What can be done?"**

**2. Genetic counseling in chromosomal congenital anomalies**

Other chromosomal anomalies are structural, such as deletions, duplications, inversions, insertions, translocations, etc. (**Figures 2** and **3**). They are rare and require different diagnosis strategies, counseling, and management of the case.

Possible alternatives for screening ("Prenatal Biochemical and Ultrasound Markers in Chromosomal Anomalies") and diagnosis ("Genomic Testing for Prenatal Clinical Evaluation of Congenital Anomalies") are presented in detail in different chapters, due to their marked importance in genetic testing and counseling.

In the current section, we aim to cover several genetic counseling concepts in a few hypothetical situations of congenital anomaly with underlying chromosomal cause. Pre- and posttesting counseling are a prerequisite of all genetic counseling, but the genetic consult comprises also of a detailed assessment of medical history, psychosocial assessment, and family history, which we are not focusing on here [3, 6, 7].

The possible mechanism by which the chromosomal anomalies occur is usually due to errors in the cell division cycles: nondisjunction in the maternal meiotic division I, and, less frequently, paternal origin [8] or meiosis II [9].

The etiology is mostly unclear, but the probability of chromosomal anomalies increases with maternal age [4], and this is one of the most common etiological factors. Predisposition to

oocyte aneuploidy is also seen in young women, gene expression alteration due to environmental factors and the influence of follicle-stimulating hormone (FSH) being possible culprits [10]. It is yet uncertain if the paternal age contributes to the risk of aneuploidy, if at all [11]. The contribution of different occupational or environmental factors is insufficiently

Prenatal Genetic Counseling in Congenital Anomalies http://dx.doi.org/10.5772/intechopen.74394 447

Aneuploidies are most frequent causes of mental retardation and pregnancy loss [9]. It comes as no surprise that the chance of reoccurrence is one of the most relevant aspects of genetic

(a) Complete chromosomal, especially autosomal trisomies, when parents are not carriers of

Recurrence risk in the absence of parent translocations follows the empirical risk—the risk measured in the general population, generally evaluated around 1% for the most common trisomy [12] and increases with age for trisomy 21. For other trisomies, the recurrence risk seems lower. Recurrence rates are rather difficult to estimate in sexual aneuploidies. Subjects with Down syndrome are generally infertile, but they have a significant risk of aneuploidy

(b) Chromosomal trisomies with one of the parents being a carrier of a chromosome 21

Down syndrome translocations are present in less than 4% of the cases. Translocations can occur de novo. For transmitted translocations, the recurrence risk depended on the affected parent: for instance, depending on the involved translocated chromosomes, if the mother is the balanced carrier, the risk is to that of the father, without any known reason for the discrep-

Generally, mosaicism cases have the lowest frequency contributions to the total of the trisomies. Mosaicism can occur de novo in the offspring, but parental germ line mosaicism contributes to the recurrence risk [15]. Reduced mosaic [16], meaning low percentage of modified cell lines, or partial trisomy [17], equivalent with duplication, generally has a better prognosis

The couple must be informed that there is no prophylaxis or treatment to correct the aneuploidy, but genetic counseling can provide the support for medically informed decisions to

If the couple wishes to keep a pregnancy with chromosomal disorder, they must be informed on the obstetrical complications that may arise, the life expectancy, and the natural history of

A trisomy prenatal case, especially 13 or 18, may present with different obstetrical challenges: miscarriage and stillbirth are more frequent than compared to the general population. Structural anomalies of the fetuses lead to a negative prognosis after birth and low life

by comparison with a homogenous complete trisomy, but this is not a rule [18].

ancy. A balanced translocation t(21,21) has 100% recurrence risk [14].

documented.

counseling.

translocations

translocation

(c) Mosaicism

expectancy [19].

recurrence in their offspring [13].

guide the management of the case.

the disease neonatally and into adulthood.

**Figure 2.** Karyotype 45,XX,rob(13;22)(q10;q10)—Robertsonian translocation.

**Figure 3.** Karyotype 46,XY,t(1;15)(p36.3;q26.1)—reciprocal translocation.

oocyte aneuploidy is also seen in young women, gene expression alteration due to environmental factors and the influence of follicle-stimulating hormone (FSH) being possible culprits [10]. It is yet uncertain if the paternal age contributes to the risk of aneuploidy, if at all [11]. The contribution of different occupational or environmental factors is insufficiently documented.

Aneuploidies are most frequent causes of mental retardation and pregnancy loss [9]. It comes as no surprise that the chance of reoccurrence is one of the most relevant aspects of genetic counseling.

(a) Complete chromosomal, especially autosomal trisomies, when parents are not carriers of translocations

Recurrence risk in the absence of parent translocations follows the empirical risk—the risk measured in the general population, generally evaluated around 1% for the most common trisomy [12] and increases with age for trisomy 21. For other trisomies, the recurrence risk seems lower. Recurrence rates are rather difficult to estimate in sexual aneuploidies. Subjects with Down syndrome are generally infertile, but they have a significant risk of aneuploidy recurrence in their offspring [13].

(b) Chromosomal trisomies with one of the parents being a carrier of a chromosome 21 translocation

Down syndrome translocations are present in less than 4% of the cases. Translocations can occur de novo. For transmitted translocations, the recurrence risk depended on the affected parent: for instance, depending on the involved translocated chromosomes, if the mother is the balanced carrier, the risk is to that of the father, without any known reason for the discrepancy. A balanced translocation t(21,21) has 100% recurrence risk [14].
