Cytogenetics

Question 1

There are 10 indications for a blood karyotype. Name as many as you can

Answer 1

primary amenorrhea
infertility
recurrent pregnancy loss/stillbirth
ambiguous genitalia
small testes, delayed puberty in males
short stature
dysmorphic features, growth impaired
mental retardation
family history of chromo. rearrangement
hematological malignancy

Question 2

when would you do a skin biopsy?

Answer 2

chromosomal mosaicism suspected

Question 3

give 5 steps of a karyotype

Answer 3

1. culture tissues/cells
2. stimulation cell division with PHA
3. mitotic block with colcemid
4. treat w/ trypsin to release proteins
5. stain with Giemsa

Question 4

what changes does a karyotype detect?

Answer 4

> 5 Mb changes

Question 5

what chromo changes can be balanced rearrangment (4)

Answer 5

inversions
insertions
translocations
robertsonian translocation

Question 6

what is the recurrence issue w/ balanced?

Answer 6

offspring of carrier at risk to unbalanced

Question 7

phenotypic consequences of translocation?

Answer 7

rarely any at all bc between non homologous

offspring at risk of being unbalanced

Question 8

pericentric vs. paracentric

Answer 8

peri - includes centromere. can have unbalanced children

para - doesn’t include centromere. only balanced offspring

Question 9

what chromo changes can happen in unbalanced rearrangements

Answer 9

deletions
duplications
isochromosomes
unbalanced translocations

Question 10

deletions and duplications can occur by what mechanisms? (4)

Answer 10

abnormal segregation from inversion, insertion
translocation

NAHR

Question 11

what happens in confined placental mosaicism?

Answer 11

nondisjunction post-zygotically
zygote is trisomic
trisomy rescue - one chromosome is removed giving disomy

placental tissue from CVS is abnormal, but fetus turns out to be normal

Question 12

what are the relevant aneuploidys?

Answer 12

trisomy 13, 18, 21, Klinefelter (XXY), Turner (monosomy X)

Question 13

what are the three causes of Downs

Answer 13

freestanding trisomy 21
RT (spontaneous)
RT (parental carrier)

Question 14

List some of the clinical features of Downs in neonates

Answer 14

congenital HD
hypotonia
duodenal atresia
hematologic issues

Question 15

list some of the childhood clinical features of Downs

Answer 15

developmental delay
mental R
strabismus
alantoaxial instability
slow growth
hearing loss
hypothyroidism
leukemia

Question 16

list some of the adult issues in downs

Answer 16

premature aging
alzheimers
shortened life expectancy

Question 17

what is down recurrence risk?

Answer 17

1-4% for any nondisjunction

downs responsible for half that

Question 18

clinical features of trisomy 18?

Answer 18

clenched hands
congenital HD
small for gestational age
abnormal facial features
feeding problems
failure to thrive

Question 19

prognosis for trisomy 18?

Answer 19

30% survive one month
10% one year
Death secondary to apnea, aspiration, seizures
Survivors profoundly MR

Question 20

clinical features of trisomy 13?

Answer 20

polydactyl
microcephaly
holoprosencephaly
scalp defects
hypotelorism, micropthalmia, midline facial clef

Question 21

prognosis for trisomy 13?

Answer 21

40-50% survive one month
10% one year
Death secondary to apnea, aspiration, seizures
Survivors profoundly MR

Question 22

turner syndrome genetics?

Answer 22

45,X (50%)
mosaic (40%) (45,X/46XY or XX)
others from strxal X aberrations, translocations, isochromosome Xq

Question 23

clinical features of newborn with turner syndrome?

Answer 23

nuchal skin redundancy
low posterior hairline
upturned earlobes 
puffy hands and feet
inverted nails
broad chest

Question 24

birth defects in turner syndrome?

Answer 24

congenital heart disease
kidney strxal abnormalities
lympedema
cystic hygroma
nuchal redundancy

Question 25

natural history of turner syndrome?

Answer 25

``` small stature (secondary to SHOX hemizygosity) ovarian failure --> primary amenorrhea, infertility no mental R but some mild disability in visuo-spatial ```

Question 26

genetics of klinefelter syndroms?

Answer 26

47,XXY or more X chromosomes (less severe) meiotic nondisjunction maternal > paternal weak maternal age effect

Question 27

clinical features of klinefelter

Answer 27

normal in childhood then get tall stature most develop normal cognitively some get malignancy, CV issues, immunogenic

Question 28

why are microdeletions and microduplications important in clinical genetics?

Answer 28

important cause of cognitive disability, congenital anomalies, genetic variation

Question 29

what are some uses of FISH

Answer 29

delineate translocations identify marker chromosomes detect deletions or duplications can use in dead/nondividing cells

Question 30

what are some uses/nonuses for array CGH

Answer 30

can't see low level mosaicism or balanced rearrangements autism or pt with unexplained MR CNV analysis

Question 31

what is the williams syndrome deletion?

Answer 31

7q11.23

Question 32

what is the williams syndrome phenotype?

Answer 32

``` overlyfriendly behavior unusual facial features growth impairment congenital HD (SVAS, elastin arteriopathy) urinary tract abnormalities endocrine issues ```

Question 33

genotype-phenotype correlation?

Answer 33

ELN deletion - elastin. SVAS LIMK1 deletion - lim kinase. visuospatial cognition

Question 34

what is the deletion in DiGeorge syndrome?

Answer 34

22q11

Question 35

what is the DiGeorge phenotype?

Answer 35

``` congenital HD cleft palate hypocalcemia from hypoparathyroidism immune deficincy developmental delay behavioral issues ```

Question 36

how common is DiGeorge?

Answer 36

most common microdeletion

Question 37

What is the Cri du Chat phenotype?

Answer 37

high pitched cry microcephaly MR characteristic facial features

Question 38

Cri du Chat phenotype?

Answer 38

terminal deletion on chromosome 5p

Question 39

Cri du Chat genotype-phenotype

Answer 39

fine positional mapping allows for delineation of what deletions lead to what phenotype

Question 40

what is worse -- a large or small pericentric inversion and why

Answer 40

Large inversions are less severe Crossing over gives less loss of chromosomal material Small inversions are more severe Crossing over gives more loss of chromosomal material