7. Genetic Disorders for BSN 2nd year.pptx

Pathophysiology of BSN

1. GENETIC DISORDERS By Dr Remisha Zahid Shah Department of Pathology

2. TERMINOLOGY Hereditary disorders- derived from one’s parents , are transmitted in the gametes through the generations,and therefore are familial. C ongenital disorders - “present at birth.” Some congenital diseases are not genetic (e.g., congenital syphilis). Not all genetic diseases are congenital; the expression of Huntington disease, for example, begins only after the third or fourth decade of life.

3. MENDELIAN DISORDERS: DISEASES CAUSED BY SINGLE-GENE DEFECTS

4. Mendelian disorders result from mutations in single gene Whether a given mutation will have an adverse outcome is influenced by compensatory genes and environmental factors Some autosomal mutations produce partial expression in heterozygotes and full expression only in homozygotes (e.g., sickle cell disease). Mendelian traits can be dominant, recessive, or codominant.

5. TRANSMISSION PATTERN OF SINGLE GENE DISORDERS

6. AUTOSOMAL DOMINANT Heterozygous state Either sex can be affected Atleast One affected parent Late onset

7. AUTOSOMAL RECESSIVE Homozygous state Either sex can be affected Both parents are obligate carrier Early onset Genes involved often encode catalytic proteins

8. Chromosomal disorders More frequent 1 in 200 Cytogenetic disorders may be due to alterations in the number or in the structure of chromosomes. Human somatic cells contain 46 chromosomes 2n; these comprise 22 homologous pairs of autosomes and two sex chromosomes, XX in the female and XY in the male.

9. KARYOTYPING The study of chromosomes Phototgraphic representation of a stained metaphase spread in which chromosomes are arranged in order of decreasing length Karyotypes are given as total number of chromosomes, followed by the sex chromosome complement, and then abnormalities in ascending numerical order

10. Euploid - any exact m ultiple of haploid number n Polypoid - 3n , 4n generally result in spontaneous abortions Aneuploid - any number that is not an exact multiple Nondisjunction of homologous pair of chromosome at first meiotic division When nondisjunction occurs at the time of meiosis , the gametes formed have either an extra chromosome(n + 1) or one less chromosome (n − 1). Numerical Disorders in Chromosomes

11. Numerical disorders Monosomy associated with one less normal chromosome Trisomy associated with one extra chromosome

12. Numerical disorders of chromosomes result from errors during cell division. Monosomy and trisomy usually result from chromosomal nondisjunction during gametogenesis (the first meiotic division) Monosomy of autosomes usually results in early fetal death and spontaneous abortion Trisomies are better tolerated, and similar imbalances in sex chromosomes are usually compatible with life.

13. Down Syndrome Trisomy 21 (Down Syndrome) M ost common chromosomal disorder (1 in 700 births ) M ajor cause of mental retardation About 95% have a complete extra chromosome 21 ( 47,XY,+21). In 95% of these cases, the extra chromosome is maternal in origin The incidence is strongly influenced by maternal age: 1 in 1550 births in women younger than 20 years; 1 in 25 births in women older than 45 years .

14. Klinefelter syndrome Klinefelter syndrome is male hypogonadism associated with two or more X chromosomes and at least one Y chromosome. The Y chromosome is both necessary and sufficient for male development. Regardless of the number of X chromosomes, the presence of a single Y drives development toward the male sex. 47,XXY is most common (i.e., 90% of cases) With the remainder being mosaics (e.g., 46,XY/47,XXY).

15. Clinical features include: Male infertility Eunuchoid body habitus Minimal or no mental retardation Failure of male secondary sexual characteristics Gynecomastia with 20-fold increased risk of breast cancer relative to normal males Female distribution of hair Atrophic testes Plasma follicle-stimulating hormone and estrogen levels elevated Testosterone levels low

16. TURNER SYNDROME Turner syndrome is hypogonadism in phenotypic females resulting from complete or partial monosomy of X chromosome 45,X occurs in 57% of cases

17. Clinical features include: Lymphedema of neck, hands, and feet Webbing of neck (due to lymphatic dilation during development) Short stature Broad chest and widely spaced nipples Primary amenorrhea Failure of the development of normal secondary sex characteristics Severely atrophic and fibrous ovaries (streak ovaries) Congenital heart disease, particularly aortic coarctation .

18. Thank you