Numerical Chromosomal Abnormalities

I. POLYPLOIDY is the addition of extra haploid sets of chromosomes (i.e., 23) to the normal diploid set of chromosomes (i.e., 46).

A. Triploidy is a condition in which cells contain 69 chromosomes. It results in spontaneous abortion of the conceptus or only brief survival of the liveborn infant after birth. Triploidy occurs as a result of either a failure of meiosis in a germ cell (e.g., fertilization of a diploid egg by a haploid sperm) or dispermy (two sperm that fertilize one egg).

B. Tetraploidy is a condition whereby cells contain 92 chromosomes. It results in spontaneous abortion of the conceptus. Tetraploidy occurs as a result of failure of the first cleavage division.

II. ANEUPLOIDY is the addition of one chromosome (trisomy) or loss of one chromosome (monosomy). Trisomy usually results in spontaneous abortion of the conceptus; however, trisomy 13 (Patau's syndrome), trisomy 18 (Edwards' syndrome), trisomy 21 (Down syndrome), and Klinefelter's syndrome (47, XYY) are found in the liveborn population. Monosomy usually results in spontaneous abortion of the conceptus; however, monosomy X chromosome (45, X; Turner's syndrome) is found in the liveborn population. Aneu-ploidy occurs as a result of nondisjunction during meiosis (Figure 22-1).

A. Trisomy 13 (Patau's syndrome) is characterized by profound mental retardation, congenital heart defects, cleft lip and palate, omphalocele, and Polydactyly. Infants usually die soon after birth.

B. Trisomy 18 (Edwards' syndrome) is characterized by mental retardation, congenital heart defects, small facies and prominent occiput, overlapping fingers, and rocker-bot-tom heels. Infants usually die soon after birth.

C. Trisomy 21, or Down syndrome (Figure 22-2 A-C), is characterized by moderate mental retardation, microcephaly, microphthalmia, colobomata, cataracts and glaucoma, flat nasal bridge, epicanthic folds, protruding tongue, simian crease in the hand, and congenital heart defects. Alzheimer's neurofibrillary tangles and plaques are found in Down syndrome patients who are older than 30 years. Acute megakaryocyte leukemia (AMKL) is frequently present.

1. This syndrome is the most common type of trisomy; its frequency increases with advanced maternal age.

2. Trisomy 21 is associated with low «-fetoprotein levels in amniotic fluid or maternal serum.

3. A specific region on chromosome 21 seems to be markedly associated with nu-

Cell division** of meiosis I

Meiosis II

Meiosis II

tfCeW division* of meiosis I

tfCeW division* of meiosis I

¡X Cell division ryof meiosis W^

¡X Cell division ryof meiosis W^

Cell division^'

Cell division^'

Trisomy Zygote

D Sperm Oocyte Zygote

23 23 46

Sperm Oocyte Zygote

23 24 47

Sperm Oocyte Zygote

23 22 45

Figure 22-1. (A) Normal meiotic divisions (I and II) producing gametes with 23 chromosomes. (B) Nondisjunction occurring in meiosis I produces gametes with 24 and 22 chromosomes. (C) Nondisjunction occurring in meiosis II produces gametes with 24 and 22 chromosomes. (D) Although nondisjunction may occur in either spermatogenesis or oogenesis, there is a higher frequency of nondisjunction in oogenesis. In this schematic, nondisjunction in oogenesis is depicted. If an abnormal oocyte (24 chromosomes) is fertilized by a normal sperm (23 chromosomes), a zygote with 47 chromosomes is produced (i.e., trisomy). If an abnormal oocyte (22 chromosomes) is fertilized by a normal spenn (23 chromosomes), a zygote with 45 chromosomes is produced (i.e., monosomy).

merous features of trisomy 21; this region is called Down syndrome critical region (DSCR). The following genes have been mapped to the DSCR (although their role is far from clear): carbonyl reductase, SIM2 (a transcription factor), p60 sub-unit of chromatin assembly factor, holocarboxylase synthetase, ERG (a proto-oncogene), GIRK2 (a potassium ion channel), and PEP19 (a calcium-dependent signal transducer.

4. Trisomy 21 may also be caused by a chromosomal translocation (see Chapter 23 III B) between chromosomes 14 and 21 [i.e., t(14;21)j.

D. Klinefelter^ syndrome, or 47, XXY (Figure 22^2 D), is a trisomic condition found only in males and characterized by hypogonadism, sterility, gynecomastia, elevated gonadotropin levels, and eunuchoid habitus.

E. Turner's syndrome (monosomy X; 45,X; Figure 22^2 E) is a monosomic condition

Eunuchoid Habitus

Figure 22-2. (A) An infant with Down syndrome. Note the flat nasal bridge, epicanthic folds, and protruding tongue. (13) Hand of a Down syndrome patient showing the simian crease. (C) Radiograph of hand in Down syndrome showing the curved fifth digit and malformation of the middle phalange of the fifth digit. (D) A 14-year-old hoy with Klinefelter^ syndrome (47,XXY). Note the hypogonadism and eunuchoid habitus. (E) A 14-year-old girl with Turner's syndrome (45,X). Note the webbed neck (due to delayed maturation of lymphatics), shield chest, and pinpoint nipples. (A, B, C, and E, from Smith DW, Jones KL: Recognizable Patterns of Human Malformation, 3rd ed. Philadelphia, WB Saunders, 1982, pp 13 and 75. D, fcom Salmon MA, Lindenbaum RH: Developmental Defects and Syndromes. Aylesbury, England, HM & M Publishers, 1978, p 372.)

Figure 22-2. (A) An infant with Down syndrome. Note the flat nasal bridge, epicanthic folds, and protruding tongue. (13) Hand of a Down syndrome patient showing the simian crease. (C) Radiograph of hand in Down syndrome showing the curved fifth digit and malformation of the middle phalange of the fifth digit. (D) A 14-year-old hoy with Klinefelter^ syndrome (47,XXY). Note the hypogonadism and eunuchoid habitus. (E) A 14-year-old girl with Turner's syndrome (45,X). Note the webbed neck (due to delayed maturation of lymphatics), shield chest, and pinpoint nipples. (A, B, C, and E, from Smith DW, Jones KL: Recognizable Patterns of Human Malformation, 3rd ed. Philadelphia, WB Saunders, 1982, pp 13 and 75. D, fcom Salmon MA, Lindenbaum RH: Developmental Defects and Syndromes. Aylesbury, England, HM & M Publishers, 1978, p 372.)

found only in females and characterized by hypogonadism, congenital heart defects, webbed neck due to delayed maturation of lymphatics, shield chest, pinpoint nipples, edema of the hands and feet, aortic coarctation, ovarian fibrous streaks (i.e., infertility), and growth retardation. This syndrome is a common cause of primary amenorrhea.

Getting Back Into Shape After The Pregnancy

Getting Back Into Shape After The Pregnancy

Once your pregnancy is over and done with, your baby is happily in your arms, and youre headed back home from the hospital, youll begin to realize that things have only just begun. Over the next few days, weeks, and months, youre going to increasingly notice that your entire life has changed in more ways than you could ever imagine.

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