Chromosomal Abnormalities IISDK

November 3, 2012

II- STRUCTURAL CHROMOSOMAL ABNORMALITIES

Theses are group of problems that is caused by the structural abnormalities of the chromosomes.

Structural abnormalities may be Balanced or unbalancedBalanced. Where there is no loss or gain of chromosome materialUn Balanced. An `unbalanced’ translocation means that an

individual has more or less chromosomal material than usual.(Loss or gain of genetic materail)

Structural abnormalities may occure in Germ cell or Somatic cells. Those that happen in germ line such as cause difficulties in egg or sperm development

and normal development of a zygote. This can be transferred to next generations

Those happen in Somatic cells can cause Cancer but are not transferred to next generation.

II- STRUCTURAL ABNORMALITIES

Translocation Reciprocal transloations Robertsonian Translocation

Deletion and microdeletion Duplication Inversion

Pericentric inversion Paracentric inversio

Insertion Ring chromosome Isochromosome Chromosomal breakage/Instability: (e.g. Fanconi anemia, Bloom

syndrome)

Types of Structural Abnormalities

Types of Structural Abnormalities

Translocation A fragment of a chromosome is moved

("trans-located") from one chromosome to another - joins a non-homologous chromosome.

Translocation are of 2 typesReciprocal translocationsRobertsonian translocations

a- Reciprocal translocations

http://upload.wikimedia.org/wikipedia/commons/c/cb/Translocation-4-20.png

From Balanced to unbalanced Translocation

Examples of Reciprocal Abnormalities

• Reciprocal Translocation of Chromosome 9 and 22(Produces Philadelphia Chromosome). This is because that the break occurred at an important gene which is actually an oncogene called “abl” oncogene this leads to CML(Chronic Myeloid Leukemia)

• Reciprocal Translocation between Chromosome 8 and 14 result in overproduction of “myc” oncogene this leads to Burkitts Lymphoma.

b- Robertsonian translocations

Robertsonian translocations

Down Syndrome

Traditional type(95%) that is trisomy 21 an extra 21 chromosome

due to non disjunction.

Robertsonian Translocation Trisomy 21(5%). that is an extra q

arm of chromosome 21 on chromosome 14.

In this case one of the parent may have Robertsonian

Translocation and this is the cause of repeated abortions and

miscarriage(Pregnancy loss).

So a female with a down child and repeated abortions might have

Robertsonian Translocation

Deletion

Cri Du Chat: A specific Terminal deletion of a small portion of “chromosome 5”

These children have severe mental retardation, a small head with unusual facial features, and a cry that sounds like a distressed cat.

Terminal Deletion/ Cri Du Chat

Wolf- Hirschhorn Syndrome

Interstitial Deletion

• Prader-Willi and Angelman Syndrome• Deletion at chromosome 15.

Angelman, Prader-Willi syndromes

• Usually caused by large (megabase+) interstitial deletions of 15q11-q13

• Delete maternal chromosome = AS• Delete paternal chromosome = PWS

Symptoms of Angelman Syndrome

• Developmental delay• Functionally severe Speech impairment• Movement or balance disorder• Behavioral uniqueness: any combination of frequent

laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements

• Short attention span

What is Prader-Willi Syndrome Prader-Willi syndrome is caused by the absence of

normally active genetic material on the long arm of chromosome 15. Deletion on the paternal chromosome 15

Prevalence: 1:12,000- 15,000 (both sexes, all races)

Symptoms of Prader-Willi Syndrome

• Poor weight gain in infancy • Excessive or rapid weight

gain between 1 and 6 • Delayed sexual maturity• Mild to moderate mental

retardation• Obsession with food

Duplication/ Fragile X Syndrome

If the fragment joins the homologous chromosome, then that region is repeated

Example Fragile X: one of the most common form of mental retardation.

The X chromosome of some people is unusually fragile at one tip - seen "hanging by a thread" under a microscope.

Duplication/ Fragile X Syndrome

Duplication/ Fragile X Syndrome

• Moderate to sever mental retardation• Speech delay, short attention, hyperactivity• Poor motor coordination and mouthing objects• Poor socialization, temper tantrum• Mood disorder (bipolar), schizophrenia

Duplication/ Fragile X Syndrome

Types of inversion• Two types1. Peri-centric. When inversion include the centromere is called

peri-centric inversion.2. Para-centric. When inversion do not include the centromere is

called para-centric inversion.

Peri-centric Inversion of chromosome 16 & Small Partial trisomy of 16q.

• A male infant born with full term pregnancy has• Hypospadiasis• Ambiguous genitalia• Poor sucking reflex• Poor growth• Microcephaly• Wide set eyes and depressed nasal bridge.

• This baby father was suffering from Peri-centric inversion of chromosome 16 that leads to his son with double material at 16q causing small partial trisomy.

Ring chromosome A ring chromosome is a chromosome whose

arms have fused together to form a ring. Ring chromosomes may form in cells

following genetic damage by mutagens like radiation, they may also arise spontaneously during development.

http://upload.wikimedia.org/wikipedia/en/0/00/Ring_chromosome.gif

Isochromosome

An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm.

In a Robertsonian translocation fusion occurs at the:

A. Telomeres.B. Centromeres.C. Histones.D. Ends of the long arms.

Dysmorphic features and/or developmental delay 

Fetal / neonatal death, with multiple congenital malformations or dysmorphic features. 

Indeterminate gender or ambiguous genitalia, amenorrhoea, infertility etc. 

Recurrent miscarriages - if a couple have had 3 or more miscarriages - both members of the couple should be tested.

When karyotyping is needed

Known or suspected family history of chromosome abnormality (e.g. Down syndrome or Edwards syndrome), where the karyotype of the affected individual is not known or not available. 

Known familial chromosome rearrangements e.g. Robertsonian or reciprocal translocations. 

Terminated fetus, for confirmation of an abnormal cytogenetic result diagnosed previously. 

Raised maternal/ paternal age. Ultrasound marker(s) indicative of chromosome

abnormality Previous fetus/child with chromosome

abnormality. Parent is known to carry a chromosome

rearrangement. Positive maternal serum or ultrasound screening

for Down syndrome.

Indications for fetal karyotyping

A common example is chromosome analysis of amniotic fluid.

Amniotic fluid is the developing baby’s urine and trophoblastic secretions and therefore contains cells from the baby.

Chromosome analysis can also be performed on blood, skin cells, and other tissues.

How to do Chromosome Analysis

Summary• In each human cell, except the egg and sperm cells, there are 46 paired

chromosomes of varying size• • One chromosome of each pair is inherited from each parent• • The autosomes are chromosomes numbered 1-22 (largest to smallest)• • The two sex chromosomes are called X and Y• • Egg cells contain 23 chromosomes, made up of 22 autosomes and an X• • Sperm cells contain 23 chromosomes, made up of 22 autosomes and an X or a Y• • When the egg and sperm join at conception, the baby will have 46 chromosomes

in its cells, just like the parents• • Changes in the number, size or structure of chromosomes in the cells of an

individual may cause a chromosomal condition that affects growth, development and health

• A particular type of chromosomal structural change is called a translocation. There are two different types of translocations:

• Reciprocal translocation - material is exchanged between any of the chromosomes and involves pieces of any size

• Robertsonian translocation - material is exchanged between chromosomes 13, 14, 15, 21 and 22

• Where there does not appear to have been any loss or gain of chromosome material, the translocation is described as balanced

• An unbalanced translocation means that an individual has more or less chromosomal material than usual

Summary

Thank You