MCP 3 Flashcards
1. Discuss the different types of numerical and structural chromosome abnormalities and explain how they are important clinically 2. describe syndromes resulting from chromosomal aneuplodies 3. describe the clinical significance of trans locations, deletions, duplication and inversions
Euploidy
multiples of one complete chromosome complement
Aneuploidy
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
Basic nomenclature of chromosomes
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
Trisomy 13
confirmed analysis ed by karyoty
Mosaicism
- 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
Name the three most common autosomal trisomies
- Down syndrome 21
- Patau Syndrome 13
- Ewards syndrome 18
Clinical features of Down Syndrome
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
List the systems affected by Down syndrome
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
Clinical features- Trisomy 13: Patau Syndrome
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
clinical features- Trisomy 18: Edwards syndrome
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
Why are sex chromosome aneuplodies more common and less sever than autosomal aneuplodies?
because of X inactivation and limited number of genes present on the Y chromosome
XXX Female (Triple X syndrome)
- 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
XYY Male
- 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
Klinefelter Syndrome; 47 XXY
- 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
Turner Syndrome: 45, X
- 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