MCP 3

Question 1

Euploidy

Answer 1

multiples of one complete chromosome complement

Question 2

Aneuploidy

Answer 2

gain or loss of chromosome equaling less than one complete complement (i.e. trisomy, monosomy etc)

• most are incompatible with life and will terminate spontaneously
• only monosomy compatible with life is 45 X
• aneuplodies are usually not inherited but are due to meiotic or mitotic nondisjunction

Question 3

Basic nomenclature of chromosomes

Answer 3

1) total # of chromosomes
2) the sex chromosome complement
3) any chromosome abnormalities
- if two or more cell lines are present they are listed sequentially separated by a slant line

Question 4

Trisomy 13

Answer 4

confirmed analysis ed by karyoty

Question 5

Mosaicism

Answer 5

• presence of at least 2 different cell lines with at least one clear variation between them
• mosaicism is acquired because it needs two cells and by definition a zygote is one cell
• structural change: one cell line with a translocation that doesn’t occur in the other -usually the cell lines only differ by a single change

Question 6

Name the three most common autosomal trisomies

Answer 6

• Down syndrome 21
• Patau Syndrome 13
• Ewards syndrome 18

Question 7

Clinical features of Down Syndrome

Answer 7

incidence; 1/700 births
-The most common cause of mental retardation
short stature, low set ears, microcephaly, mental retardation, up slanting eyes, short hands, eye folds, protruding tongue, and usually infertile

Question 8

List the systems affected by Down syndrome

Answer 8

heart, lung, brain, endocrine (infertility), susceptibility to infectious disease (inc 15x), increased risk of leukemia x10, high frequency of AD–> most problems arise as patient ages

Question 9

Clinical features- Trisomy 13: Patau Syndrome

Answer 9

an extremely severe syndrome (usu only live first month)

• failure to thrive
• cleft palate and lip
• rocker bottom feet
• polydactylyl
• “punched out scalp”
• small head
• heart defect

Question 10

clinical features- Trisomy 18: Edwards syndrome

Answer 10

an extremely severe disease (usu only live first month)

• incidence -1/8000 live births
• LBW
• small mouth jaw
• ventricular septal defect
• hypoplasia of the muscles
• prominent occiput
• rocker bottom feet
• crossed finger -DISTINCTIVE hand sign thumb tucked in three fingers over it and pinky in the back

Question 11

Why are sex chromosome aneuplodies more common and less sever than autosomal aneuplodies?

Answer 11

because of X inactivation and limited number of genes present on the Y chromosome

Question 12

XXX Female (Triple X syndrome)

Answer 12

• 1/1000 births
• usually due to maternal meiosis I error
• average to tall stature (remember extra pseudoautosomal gene –>taller)
• learning deficits possible
• some fertility problems
• often go undetected throughout life

Question 13

XYY Male

Answer 13

• 1/1000 male live births
• failure of paternal meiosis (UNIQUE)
• tall stature
• normal intelligence
• normal fertility
• clinically indistinguishable from 46, XY
• often go undetected through life
• originally thought to be more prone to crime, but not true

Question 14

Klinefelter Syndrome; 47 XXY

Answer 14

• 1/1000 male live births
• 50% due to meiosis I error in father
• tall stature
• infertility –> small testicles, hyalinized testicular tubules and azoospermia
• some female characteristics may develop (enlarged breasts and pear shaped adipose distribution)
• learning deficit possible

Question 15

Turner Syndrome: 45, X

Answer 15

• only monosomy compatible with life
• incidence 1/5000 live female births
• short stature
• webbed neck –> in utero leads to cystic hygroma
• at birth edema of hands and feet; after birth short hands and fingers
• increased carrying angle of the elbow (cubitus valgus)
• shield chest (breasts far apart)
• low posterior hairline
• usually normal intelligence though may have learning difficulties
• usually infertile - but not always - can use egg donor because producing eggs seems to be the problem

Question 16

Individuals with a 45,X/46,XY mosaicism

Answer 16

-male phenotype okay
-female phenotype (Turner)
increased risk of gonadoblastoma –> usually pre-emtive surgery to remove gonads is performed - this is why diagnosis is very important!

Question 17

Turner syndrome: issues

Answer 17

• growth hormones
• monitor for heart malfunctions
• karyotype to be sure no Y chromosome is present
• counseling for probable infertility -possible with egg donor

Question 18

Androgen insensitivity

Answer 18

• also known is “testicular feminization”
• caused by a mutation of the androgen receptor gene located on the long arm of the X chromosome
• phenotypically normal female with testes
• infertility

Question 19

XX “Male”

Answer 19

• congential adrenal hyperplasia (lack of 21 alpha hydroxylase)
• autosomal recessive condition
• mutation results in overproduction of androgen in female fetus
• In uteruo exposure causes virulization of fetus - normal ovaries and internal genitalia, but ambiguous external
• can be due to either CAH in fetus or mother

Question 20

XX male

Answer 20

• 1/20,000 live births
• X-Y recombination near the pseudoautosomal region
• usually normal possible klinefelter phenotype
• the reciprocal translocation TDF/SRY is replaced by Xp material which is transmitted to a child) the result is a Turner female phenotype with an apparent 46,XY karyotype

Question 21

Structural abnormalities can be ..

Answer 21

balanced: all the material is present but rearranged
unbalanced: some of the material is missing or duplicated –> more worrisome

Question 22

Deletion

Answer 22

• loss of part of a chromosome
• leads to partial monosomy
• large deletions may lead to developmental delay and mental retardation and abnormal features
• size is not as important as which genes are missing and how many

Question 23

Terminal deletion

Answer 23

the distal end of one arm of a chromosome is lost - this deletion only requires one break

Question 24

Interstitial deletion

Answer 24

an integral region of the chromosome is lost - this type of deletion requires two breaks

Question 25

Wolf-Hirchhorn syndrome [4p-]

Answer 25

- microcephaly - micrognathia - hypotonia - epicanthal folds - startled or suprised look - long nose squared off end - short stature - developmental delay - arched brows -greek warriors helmet syndrome

Question 26

Duplication

Answer 26

- additional copy of the chromosome segment - results in partial trisomy - can be inherited but usually sporadic

Question 27

Terminal duplication

Answer 27

-extra material at one end of a chromosome- usually a direct duplication of the material adjacent to it

Question 28

Interstitial duplication

Answer 28

-extra material within a chromosome -again usually a copy of adjacent regions

Question 29

translocation

Answer 29

- rearrangements involving two or more nonhomologous chromosomes - each chromosome breaks once and the pieces exchange places producing two or more derivative chromosomes - as long as the break does not occur in an important coding gene the rearrangement should be clinically benign

Question 30

what is the significance of a balanced translocation

Answer 30

individual issues -increased risk that another pregnancy will have an unbalanced chromosome complement -increased risk of infertility or spontaneous loss -increased risk of an abnormal live born 10% for each pregnancy -relativity common (1/500) -carriers are phenotypically normal translocation can be inherited or de novo - can be seen in families

Question 31

Robertsonian translocations

Answer 31

a variant on the standard-they only occur between two acrocentric chromosomes and appear as a fusion of the long arms of the centromere - may be between homologous and non homologous chromosomes - translocation results in the loss of both short arms but because this material is present on the remaining 8 acrocentric chromosomes the loss as a result is not deleterious

Question 32

Inversion

Answer 32

- reversal of a chromosomal segment with respect to the normal gene arrangement - requires a minimum of two breaks - majority are balanced but like translocations can be unbalanced

Question 33

Pericentric inversion

Answer 33

the breaks occur on opposite sides of the centromere and the segment reverses order generating a new chromosome with the same genes in a different order -also has an inversion loop --> recombination in inversion loop give rise to recombined gametes with duplication and deletion of some genes--> larger inversion more viable ironically

Question 34

paracentric inversion

Answer 34

two breaks occur on the same side of the centrome (in the same arm) such that the centromere is not involved in the rearrangement -in order for chromosomes to pair properly one chromosome must twist resulting in inversion loop - when recombination occurs may lead to dicentric (2 centromeres) or accentric (0 centromeres)

Question 35

Can more than one chromosomal abnormality appear in a single individual ?

Answer 35

yes, VERY RARE- but most likely caused by mitotic error