(c) Mosaicism

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

446 Congenital Anomalies - From the Embryo to the Neonate

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

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

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 guide the management of the case.

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 the disease neonatally and into adulthood.

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 expectancy [19].

Screening and diagnosis limitations for trisomy 13 lead to underdiagnosis of this aneuploidy. Genetic counseling should bring into discussion the viable fetuses in the second trimester (60% of the cases), when life expectancy is very hard to predict and there is no longer the alternative to terminate the pregnancy. It is crucial to inform the parents on the neonatal procedures for resuscitation, possibilities to correct certain defects so that the couple is prepared to face the trauma of having a child with lethal defect [20].

established, then the recurrence risk can be calculated. Probability of inheritance based on Mendel's principles and conditional probability (also known as Bayesian analysis, based on

Prenatal Genetic Counseling in Congenital Anomalies http://dx.doi.org/10.5772/intechopen.74394 449

The risk of expressing a monogenic disease is dependent not only on the pattern of inheritance, but also on other factors such as the incidence of the disease, the presence of other affected members, the penetrance and variable expressivity, ethnicity, and the influence of environmental factors.

An autosomal dominant disease is a condition expressed in both heterozygous, carrying one copy, and homozygous individuals, carrying two copies one from each parent. The disease is caused by a single gene defect located on an autosome. The affected individuals are usually heterozygous, and the homozygous genotype is associated with more severe features or can be lethal. Females and males exhibit the trait in approximately equal proportions and severity of clinical signs is similar between the two sexes. Both sexes are equally likely to transmit the mutation to their offspring. Mostly, the affected offsprings are descendants of an affected heterozygous and a normal parent. On average, half of the children will be heterozygous and express the disease and half will not. Rarely, homozygous are seen in autosomal dominant diseases. This status can be due to a higher frequency of a gene with mild effects, late onset (e.g. Huntington disease) or when both parents are affected (e.g. achondroplasia). Unusually, an affected homozygous parent will transmit the disease to all of his children. On the pedigree, a vertical transmission pattern is observed (**Figure 4**), and the disease phenotype is usually seen in one generation after another. The disease does not skip generations: if an individual has an autosomal disease, in most of the cases, one parent must also have it [1, 2].

Frequently, autosomal dominant disorders involve different organs and systems of the body; however, dominant conditions affecting one organ have been described (e.g., congenital cataract). The capacity of a single gene to affect unrelated organs is called *pleiotropy* (e.g., Marfan syndrome can affect the skeletal, ocular, and cardiovascular systems; some affected individuals have all features, whereas others may have almost none). In addition, the clinical features in autosomal dominant disorders can show remarkable variation between patients, even between the members of the same family. This difference between individuals is referred to as *variable expressivity* (e.g., in autosomal dominant polycystic kidney disease, some affected individuals develop renal failure in early adulthood, whereas others have just a few renal cysts that do not significantly influence renal function). Occasionally, the heterozygous and

homozygous individuals express identical phenotype (complete dominance) [2, 23].

Sometimes, a dominant mutation is inherited, but the condition it determines is not expressed. In these cases, the gene has *reduced (incomplete)penetrance.* The term penetrance is used in monogenic inheritance to indicate the probability of a gene to influence the phenotype. A number of autosomal dominant diseases show an incomplete penetrance (e.g., polydactyly), meaning that a person has the mutation but shows no evidence of a disease. A gene is *completely penetrant* if each individual who inherited the mutation expresses clinical

Bayes' theorem on probability) are used to calculate genetic risk [1].

**3.1. Autosomal dominant inheritance**

features (e.g., neurofibromatosis type I) [3].

For trisomy 18, only 10% of the neonates survive longer than 1 year. Diagnosing this trisomy though genetic testing is essential for decision-making during the neonatal life, where critical emergency interventions and choosing invasive treatments are often required [21].

Trisomy 21 has a life expectancy of almost 60 years. Following up, the patient asks for collaborations with multiple medical specialties: cardiological, ENT, ophthalmology, endocrinology, to assess possible complications. During their pediatric life, other interventions are generally symptomatic and similar to their euploid peers [22]. The parents must be prepared though through genetic counseling for the possible difficulties due to motor and cognitive delay. Support in the patient's lifestyle can also come from nongovernmental associations and patient support groups, e.g., Down Syndrome International (https://ds-int.org/ down-syndrome-your-country).
