Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

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accompanying congenital heart defects and an increased risk of gastrointestinal malformations. Approximately 1% of persons with trisomy 21 Down syndrome have mosaicism (i.e., cell populations with the normal chromo- some number and cell populations with trisomy 21); these persons may be less severely affected. Of particular con- cern is the much greater risk of development of acute leu- kemia among children with Down syndrome—10 to 20 times greater than that of other children. 3 With increased life expectancy due to improved health care, it has also been found that there is an increased risk of Alzheimer disease among older persons with Down syndrome. In the past few years, unprecedented breakthroughs have been made in the treatment of Down syndrome. These include the development of interventional and educational strategies to help affected individuals achieve their employment and independence goals based on their full potential. Several studies to determine safe and effec- tive drugs to improve cognitive ability have been initiated (Down Syndrome Research and Treatment Foundation http://lumindfoundation.org/). Several prenatal screening tests can help determine the risk of having a child with Down syndrome. 33 The most commonly used are blood tests that measure maternal serum levels of α -fetoprotein, human chorionic gonado- tropin (hCG), unconjugated estriol, inhibin A, and preg- nancy-associated plasma protein A (PAPP-A, see section on prenatal screening and diagnosis). The results of three or four of these tests, together with the woman’s age, often are used to determine the probability of a pregnant woman having a child with Down syndrome. Another test, fetal nuchal translucency (sonolucent space on the back of the fetal neck), uses ultrasonography and can be performed between 10 and 13 weeks’ gestation. The fetus with Down syndrome tends to have a greater area of trans- lucency compared with a chromosomally normal infant. The nuchal translucency test is usually used in combina- tion with other screening tests. The current standard for determining the presence of Down syndrome in the fetus is through chromosome analysis using chorionic villus sampling, amniocentesis, or percutaneous umbilical blood sampling. More recently, non-invasive screening for fetal chromosomal abnormalities using cell-free DNA obtained through a maternal blood draw has become available. Numeric Disorders Involving Sex Chromosomes Chromosomal disorders associated with the sex chro- mosomes are much more common than those related to the autosomes, save for trisomy 21. Furthermore, imbalances (excess or deletions) are much better toler- ated than those involving the autosomes. This is related in large part to two factors that are peculiar to the sex chromosomes: (1) the inactivation of all but one X chromosome and (2) the modest amount of genetic material that is carried on the Y chromosome. Although girls normally receive both a paternal and a maternal X chromosome, the clinical manifestations of X-chromosome abnormalities can be quite vari- able because in somatic cells of females only one X

chromosome is transcriptionally active while the other chromosome is inactive. 1 The process of X inactivation, which is random, occurs early in embryonic life and is usually complete at the end of the first week of develop- ment. After one X chromosome has become inactivated in a female, all cells descended from that cell have the same inactivated X chromosome. Although much of one X chromosome is inactivated in females, several regions contain genes that escape inactivation and continue to be expressed by both X chromosomes. These genes may explain some of the variations in clinical manifesta- tions seen in cases of numerical abnormalities of the X chromosome, such as Turner syndrome. Turner Syndrome Turner syndrome describes an absence of all (45,X/0) or part of one of a female’s two X chromosomes. 2,3,34–42 Some women may display a mosaicism with one or more additional cell lines. This disorder affects approximately 1 of every 5000 live births, and it has been estimated that almost all fetuses with the 45,X/0 karyotype are spontaneously aborted during the first trimester. 2 Characteristically, the girl with Turner syndrome is short in stature, but her body proportions are nor- mal (Fig. 6-11). Because of the absence of the ovaries, she does not menstruate and shows no signs of sec- ondary sex characteristics. There are variations in the

Small stature

Low posterior hairline and webbed neck

Broad chest with widely spaced nipples

Coarctation of aorta and bicuspid aortic valve

Poor breast development

Ovarian dysgenesis with primary amenorrhea, estrogen

Wide carrying angle of arms

and progesterone deficiencies, and infertility

Retardation of bone age

Multiple pigmented nevi

Lymphedema of hands and feet at birth and later

FIGURE 6-11. Clinical features ofTurner syndrome.