A.

What is the rate of occurrence of Down syndrome in the general population?

 

The risk for chromosome problems increases with the mother's age. The chance of having a child with Down syndrome increases over time. The risk is about 1 in 1,250 for a woman who conceives at age 25. It increases to about 1 in 100 for a woman who conceives at age 40. The risks may be higher. This is because many statistics only report live births. They do not note pregnancies with chromosome problems that ended due to pregnancy loss.

After having 1 child with Down syndrome, the chance of having another baby with Down syndrome is higher. After age 40, the recurrence risk for Down syndrome is based on the age of the mother at delivery. Most babies with Down syndrome are born to women under the age of 35. This is because women under the age of 35 have more babies than women over 35...Reference: https://www.stanfordchildrens.org/en/topic/default?id=pregnancy-over-age-30-90-P02481#:~:text=The%20chance%20of%20having%20a,The%20risks%20may%20be%20higher.

 

What are some of the common clinical features?

A. Down syndrome occurs approximately once in every 700 live births.

 

Common features include developmental delay, growth restriction, congenital heart disease (in 50%), immunodeficiency, and characteristic major and minor facial and dysmorphic phenotypic features, including upslanting palpebral fissures (82%), epicanthal folds (59%), brushfield spots on the iris, brachycephaly (75%), excess skin on the back of the neck (81%), folded or dysplastic ears (50%), a flat nasal bridge (68%), a protruding tongue, hyperextensible joints (75%), a wide gap between the first and second toes, short and broad toes, a short and incurved fifth finger, and transverse palmar creases (53%).

B.

What major genetic abnormalities are associated with Down syndrome? How might these abnormalities lead to the clinical features of the syndrome?

B. There are two major genetic abnormalities associated with Down syndrome. The most common abnormality occurs in children born to parents with normal karyotypes. It is caused by the nondisjunction of chromosome 21 during meiotic segregation, resulting in one extra chromosome 21 (trisomy 21), with 47 chromosomes on karyotyping. Alternatively, Down syndrome can be caused by DNA rearrangement resulting in the fusion of chromosome 21 to another acrocentric chromosome via its centromere. This abnormal chromosome is called a robertsonian translocation chromosome. Unlike those with trisomy 21, these individuals have 46 chromosomes on karyotyping. This type of translocation can sometimes be inherited from a carrier parent.

Both these genetic abnormalities result in a 50% increase in gene dosage for nearly all genes on chromosome 21. In other words, the amount of protein produced by all or nearly all genes on chromosome 21 is approximately 150% of normal in Down syndrome. The genes that have been shown to contribute to the Down syndrome phenotype include the gene that encodes the amyloid protein found in the senile plaques of Alzheimer disease and the one that encodes the cytoplasmic form of superoxide dismutase, which plays an important role in free radical metabolism.

C.

How might this woman’s age contribute to her risk of having a child with Down syndrome?

C. It is not known why advanced maternal age is associated with an increased risk of Down syndrome as a result of trisomy 21. One theory suggests that biochemical abnormalities affect the ability of paired chromosomes to disjoin and that these abnormalities accumulate over time. Because germ cell development is completed in females before birth, these biochemical abnormalities are able to accumulate within the egg cells as the mother ages, thereby increasing the risk of nondisjunction. Another hypothesis is that structural, hormonal, and immunologic changes occur in the uterus as the woman ages, producing an environment less able to reject a developmentally abnormal embryo. Therefore, an older uterus would be more likely to support a trisomy 21 conceptus to term. Alternatively, it is possible that a combination of these and other genetic factors may contribute to the relationship between advanced maternal age and an increased incidence of Down syndrome.