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Chromosomal Abnormalities I SDK October 21, 2013

Chromosomal Abnormalities I SDK October 21, 2013. Chromosomes. Chromosomes are tiny string-like structures in cells of the body that contain the genes Each person normally has 23 pairs of chromosomes, or 46 in all. We inherit one chromosome per pair from our mother and one from our father.

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Chromosomal Abnormalities I SDK October 21, 2013

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  1. Chromosomal Abnormalities ISDKOctober 21, 2013

  2. Chromosomes • Chromosomes are tiny string-like structures in cells of the body that contain the genes • Each person normally has 23 pairs of chromosomes, or 46 in all. • We inherit one chromosome per pair from our mother and one from our father.

  3. Chromosomal Abnormalities • However, When a baby is born with too many or too few chromosomes, or with one or more chromosomes that are missing a piece or are rearranged, is suffering from chromosomal abnormalities.

  4. Chromosomal Abnormalities • About 1 in 150 babies is born with a chromosomal abnormality. • A change in the number or structure of chromosomes can cause problems with growth, development, and function of the body’s systems. • Children with a chromosomal abnormality have mental and/or physical birth defects. • 95% of chromosomally abnormal conceptus are aborted spontaneously • Abortion mostly occurs in 1st trimester

  5. Chromosomal Abnormalities • The majority of human chromosomal abnormalities occur in the Autosomes.  • Most of these abnormalities are monosomies or trisomies.  • In the case of a monosomy, there is only one copy of each kind of chromosome instead of the usual pair of homologous chromosomes.  • With trisomy, there are three of each type of chromosome.  • All fetuses with autosomalmonosomies spontaneously abort early in pregnancy.  • Likewise, almost all fetuses with trisomies die before birth.  • Those that survive usually have multiple physical malformations, mental retardation, and relatively short lives.

  6. Chromosomal Disorders • 50% of 1st trimester miscarriages(Before 24 week) • 5% of stillbirths(from 24 week to) • 0.5% of live borns • Down syndrome—trisomy 21 • Fragile X syndrome • Somatic cell abnormalities in cancers

  7. Chromosomal Abnormalities What are chromosome abnormalities? A chromosome abnormality reflects an abnormality of chromosome number or structure. We can classify them into: I- NUMERICAL ABNORMALITIES II- STRUCTURAL ABNORMALITIES

  8. I. NUMERICAL ABNORMALITIES

  9. NUMERICAL ABNORMALITIESHOW DOES IT HAPPEN Chromosomal abnormalities in the number of chormosomes. • Euploidy • Aneuploidy

  10. NUMERICAL ABNORMALITIESHOW DOES IT HAPPEN 1.Euploidy: Cells has chromosomes multiple of 23 such as • 23, 46. 69, and 92 • These may be normal or Abnormal • Normal • Haploid cells : Gametes has 1 copy each 23 cells • Diploid cells: Somatic cells has 2 copy each 23 x2= 46 Abnormal • Tripoloidy 3 copies of each chromosome 23 x 3= 69 • 1 egg fertilized by 2 sperms • Tetra ploidy. 4 copies of each chromosome 23 x 4= 69 • 1 egg fertilized by 3 sperms

  11. 2.Aneuploidy • Deviation from normal number of chromosomes due to loss or gain of specific chromosomes. • Generally caused by “non-disjunction” of chromosome during meiosis. • It is a major cause of human reproductive failure. • Most human miscarriages are aneuploids. • All autosomal monosomies are lethel • Most of all Trisomiesare also lethel • But some Trisomies[ three copies of a particular chromosomes] are compatible with survival to term with chromosomes 13, 18, and 21.

  12. Types of Aneuploidy The different conditions of aneuploidy are: • Nullisomy - the loss of both pairs of homologous chromosomes; individuals are called nullisomics and their chromosomal composition is 2N-2. Humans with this condition will not survive. • Monosomy - the loss of a single chromosome; individuals are called monosomics and their chromosomal composition is 2N-1 • Trisomy - the gain of an extra copy of a chromosome; individuals are called trisomics and their chromosomal composition is 2N+1 • Tetrasomic - the gain of an extra pair of homologous chromosomes; individuals are called tetrasomics and their chromosomal composition is 2N+2

  13. Cause of Aneuploidy • The development of aneuploids may have arisen by a process called non-disjunction. • Non-disjunction occurs when paired chromosomes do not separate either during meiosis I or meiosis II. • The direct result of this event is that gametes develop that have too few or too many chromosomes. • If this occurs during meiosis I normal gametes are not developed, • If it occurs during meiosis II half of the gametes will be normal and the other half will be abnormal.

  14. Meiosis(Normal)

  15. Non Disjunction at Meiosis I

  16. Non Disjunction at Meiosis II

  17. Non Disjunction (Quick Review)

  18. Autosomal Chromosome Problems

  19. Down Syndrome (Trisomy 21) • First identified by Dr. John Langdon Down in 1866 • Trisomy 21 • Associated with increased maternal age • The result of an extra copy of chromosome 21. People with Down syndrome are 47, 21+.

  20. Down Syndrome (Trisomy 21) • Down syndrome affects 1:700 children and alters the child's phenotype either moderately or severely: • Characteristic facial features, short stature; heart defects • Susceptibility to respiratory disease, shorter lifespan • Often sexually underdeveloped and sterile, usually some degree of mental retardation. • Down Syndrome is correlated with age of mother but can also be the result of nondisjunction of the father's chromosome 21 in 1% cases.

  21. Clinical findings • Newborn – hypotonia , increased sleepiness , excess nuchal skin • Mental retardation • The average IQ of children with Down syndrome is around 50, compared to normal children with an IQ of 100. • Small stature • Craniofacial findings – brachycephaly ( flat occiput ) , epicanthic folds , upward slanting eyes , protruding tongue, low set ears , flat nose , low nasal bridge , high arched palate . • Short broad hands • Clinodactyly ( incurving ) little finger • ASD,VSD , PDA • Anal duodenal atresia • Happy & affectionate

  22. Clinical Features

  23. Patau syndrome(Trisomy 13) • Patau Sundrome, also known as Trisomy 13 and Trisomy D. • Is a chromosomal abnormality, a syndrome in which a patient had an additional chromosome 13 due to non-disjunction of chromosomes during meiosis. • Some are caused by Robertsonian Translocations. • The extra chromosome 13 disrupts the normal course of development, causing serious eye, brain, circulatory defects as well as cleft palate, heart and kidney defects. • . 1:5000 live births. Children rarely live more than a few months.

  24. Clinical Features • Polydactyl • Cleft Palate • Cutis Aplasia(Congenital absence of skin). is a congenital focal absence of epidermis. • Kidney Failures

  25. Patau syndrome(Trisomy 13)

  26. Edwards Syndrome (Trisomy 18) • Edward’s Syndrome also kwnon as Trisomy 18 (T18) or Trisome E. • It is a genetic disorder caused by the presence of all of an extra 18th chromosome (Trisomy 18). • It is named after John H. Edwards, who first described the syndrome in 1960. • It is the second most common autosomal trisomy, after Down Syndrome, that carries to term. • Edward’s Syndrome occurs in around one in 6,000 live births and around 80 % of those affected are female. • Children with full Trisomy 18 generally do not live more than a few months

  27. Edwards Syndrome (Trisomy 18)

  28. Clinical Features • Almost every organ system affected • Upturned Nose • Kidney Malformations • Omphalocele. • An omphalocele is a type of abdominal wall defect in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall. • Arthrogryposis • Arthrogryposis, is characterized by multiple joint contractures and can include muscle weakness and fibrosis. • Microcephaly • Underdeveloped Phalanges

  29. DiGeorge syndrome(Monosomy 22)22q11.2 deletion syndrome • Congenital thymic aplasia, and thymic hypoplasia • Is a syndrome caused by the deletion of a small piece of chromosome 22. • The deletion occurs near the middle of the chromosome at a location designated q11.2 • Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems

  30. DiGeorge syndrome

  31. Precursor T cell differentiation defect • Lack of T helper (Th) cells , Cytotoxic T cells (CTL) and T regulatory (Treg) cells • B cells are present but T-dependent B cell responses are defective • Anti-viral and anti-fungal immunity impaired • Developmental defect in the 3rd and 4th pharyngeal pouch • Results in facial defect and congenital heart disease • Treated with thymic transplant • Autosomal dominant trait

  32. Pallister-Killian Syndrome • Pallister-Killian Syndrome also known as Tetrasomy 12p Mosaicism or Pallister Mosaic Aneuplody Syndrome. • Is a genetic disorder occurring in humans. • Pallister-Killian occurs due to the presence of the anomalous extra isochromosome 12p, the short arm of the twelfth chromosome. • An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm • This leads to the development of Tetrasomy 12p. Because not all cells have the extra isochromosome, Pallister-Killian is a mosaic condition. • TETRASOMY in the smaller arm of chromosome 12. • 2n+2 or 48 chromosomes

  33. Clinical findings • Hypo/Hyper Pigmentation • Epilepsy • High Foreheads • Flat nose • Supernumerary Nipples • Psychomotor Retardation

  34. IDIC 15 (Isodicentric 15) • Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15). • Isodicentric chromosome 15 is the scientific name for a specific type of chromosome abnormality. • Individuals with isodicentric chromosome 15, or "idic(15)", have 47 chromosomes instead of the typical 46 chromosomes. • The extra chromosome is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. • Individuals with idic(15) have a total of four copies of this chromosome 15. • With extra genetic material in chromosome 15. • 47 chromosomes

  35. IDIC 15 (Isodicentric 15)

  36. Clinical Features • Epicanthal Folds in the Eye • Short Stature • Delayed Language Development • Seizures • Some are Mentally Retarded

  37. Which of the following is an example of monosomy? • 46,XX • 47,XXX • 69,XYY • 45,X

  38. Sex Chromosome(X Y) Abnormalities Male Sex Female Sex

  39. X Chromosome

  40. Y Chromosome

  41. Sex Chromosome Abnormalities • The majority of known types of chromosomal abnormalities involve Sex chromosomes. • In frequency of occurrence, they are only slightly less common than autosomal abnormalities.  • However, they are usually much less severe in their effects.  • Sex chromosome abnormalities are gender specific. 

  42. Male Sex 1. Klinefelter Syndrome • Klinefelter syndrome: males inherit one or more extra X chromosomes--their genotype is XXY.  • 1 in 660 live male births • They characteristically have relatively high-pitched voices, asexual to feminine body contours as well as breast enlargement, and comparatively little facial and body hair.  • They are sterile or nearly so, and their Testes and Prostat glands are small.  • As a result, they produce relatively small amounts of testosterone. • Higher risk of breast cancer, extragonadal germ cell tumor and autoimmune diseases • 47,XXY-90% cases • 15% cases are mosaics

  43. Male Sex 1. Klinefelter Syndrome

  44. Clinical features • Scarce beard • Pubic ,chin & axillary hair absent • Longer fingers and arms • Sterile • Delicate skin • Normal lifespan

  45. 2. XYY Syndrome • XYY syndrome males inherit an extra Y chromosome, their genotype is XYY.  • As adults, these "super-males" are usually tall (above 6 feet) and generally appear and act normal.  • However, they produce high levels of testosterone.  • During adolescence, they often are slender, have severe facial acne, and are poorly coordinated.  • They are usually fertile and lead ordinary lives as adults. 

  46. 2. XYY Syndrome

  47. Female Sex 1. Turner syndrome

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