Trisomy 21 describes three copies of chromosome 21, but is often used interchangeably with Down syndrome (DS), the constellation of clinical findings that are the result of having one additional copy of chromosome 21. Its clinical features were first characterized by Landon Down in 1866, but the etiology of the syndrome was not recognized until 1959 by Lejeune and colleagues.¹ Trisomy 21 is the most common trisomy, occurring in approximately 1 in every 700 live births.² More than 95% cases of DS are the result of nondisjunction during meiosis, and most commonly meiosis I. Because of the strong association between maternal age and nondisjunction, the extra chromosome is maternal in origin in approximately 95% of cases. Of the remaining 5% of DS children, most will be the result of an unbalanced chromosome translocation. These translocations likewise result in three full copies of chromosome 21, and, thus, the term trisomy 21 can be used for both these forms of DS. In our case example, it would be essential to have the cytogenetic report before attempting to counsel the patient. Although the type of trisomy 21 has no implications for the clinical outcome of the child, the implication for future pregnancies, which will be discussed later, is significantly different.

When counseling a patient regarding DS, it is important to emphasize that infants with DS have few features that are recognizable to the lay person, and that the absence of significant morphologic features has no prognostic significance. Table 7-1 lists the features that are commonly seen in infants with DS. Of more importance for prognosis are the structural malformations that are associated with DS. Approximately 50% of children with DS will have a congenital heart defect, and of these cardiac defects the most common is an atrioventricular septal defect (endocardial cushion defect). However, ventricular septal defects, atrial septal defects, and tetralogy of Fallot are seen commonly in children with DS. Should the patient in our case study decide to continue her pregnancy, a fetal echocardiogram should be performed between 18 and 20 weeks, gestation to assess for fetal cardiac malformations.

Structural malformation of the gastrointestinal tract occurs in approximately 5% of DS children, the most common abnormality being duodenal atresia. The association between duodenal atresia and DS is significant. Of those cases of duodenal atresia detected in the fetus, 30% will be found to have DS. Other gastrointestinal malformations that are associated with DS include imperforate anus, tracheoesophageal fistula, other intestinal atresias, and Hirschsprung disease.

For most couples the most significant concern upon hearing the diagnosis of DS is the degree of intellectual disability. The majority of DS children will have moderate intellectual disability (IQ range of 30-60), but, as in all children, there is a range of IQ which can vary from mild to severe in its degree. Couples who are undecided about whether to continue a pregnancy with DS should be referred to a Down syndrome center or to a pediatrician with expertise in managing DS children in order to understand fully the overall prognosis for an individual with DS.

When counseling a couple who have had a child with DS, it is essential that the exact type of DS be known. In the case of trisomy 21, because of a nondisjunctional event, the empiric risk of recurrence in older studies was approximately 1%.⁵ However, information from a large cytogenetic data set can be used to give more exact risks, depending on current age, and age at the time of the DS pregnancy.⁶ In general terms, the risk for a patient under 30 to have a second affected child is 8.2X the age-specific risk for DS (see Table 7-2 for age specific risks for DS). For a patient over the age of 35, the risk is 1.7X the age-specific DS risk. If the DS is because of a balanced translocation, the parents must have chromosome studies to determine who carries the balanced form of the translocation. If the mother is the carrier, the risk of recurrence is 10%, whereas if the male has the translocation, the recurrence risk is 3% or less.