Cytogenetics Flashcards
There are 10 indications for a blood karyotype. Name as many as you can
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
when would you do a skin biopsy?
chromosomal mosaicism suspected
give 5 steps of a karyotype
- culture tissues/cells
- stimulation cell division with PHA
- mitotic block with colcemid
- treat w/ trypsin to release proteins
- stain with Giemsa
what changes does a karyotype detect?
> 5 Mb changes
what chromo changes can be balanced rearrangment (4)
inversions
insertions
translocations
robertsonian translocation
what is the recurrence issue w/ balanced?
offspring of carrier at risk to unbalanced
phenotypic consequences of translocation?
rarely any at all bc between non homologous
offspring at risk of being unbalanced
pericentric vs. paracentric
peri - includes centromere. can have unbalanced children
para - doesn’t include centromere. only balanced offspring
what chromo changes can happen in unbalanced rearrangements
deletions
duplications
isochromosomes
unbalanced translocations
deletions and duplications can occur by what mechanisms? (4)
abnormal segregation from inversion, insertion
translocation
NAHR
what happens in confined placental mosaicism?
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
what are the relevant aneuploidys?
trisomy 13, 18, 21, Klinefelter (XXY), Turner (monosomy X)
what are the three causes of Downs
freestanding trisomy 21
RT (spontaneous)
RT (parental carrier)
List some of the clinical features of Downs in neonates
congenital HD
hypotonia
duodenal atresia
hematologic issues
list some of the childhood clinical features of Downs
developmental delay mental R strabismus alantoaxial instability slow growth hearing loss hypothyroidism leukemia
list some of the adult issues in downs
premature aging
alzheimers
shortened life expectancy
what is down recurrence risk?
1-4% for any nondisjunction
downs responsible for half that
clinical features of trisomy 18?
clenched hands congenital HD small for gestational age abnormal facial features feeding problems failure to thrive
prognosis for trisomy 18?
30% survive one month
10% one year
Death secondary to apnea, aspiration, seizures
Survivors profoundly MR
clinical features of trisomy 13?
polydactyl microcephaly holoprosencephaly scalp defects hypotelorism, micropthalmia, midline facial clef
prognosis for trisomy 13?
40-50% survive one month
10% one year
Death secondary to apnea, aspiration, seizures
Survivors profoundly MR
turner syndrome genetics?
45,X (50%)
mosaic (40%) (45,X/46XY or XX)
others from strxal X aberrations, translocations, isochromosome Xq
clinical features of newborn with turner syndrome?
nuchal skin redundancy low posterior hairline upturned earlobes puffy hands and feet inverted nails broad chest
birth defects in turner syndrome?
congenital heart disease kidney strxal abnormalities lympedema cystic hygroma nuchal redundancy
natural history of turner syndrome?
small stature (secondary to SHOX hemizygosity) ovarian failure --> primary amenorrhea, infertility no mental R but some mild disability in visuo-spatial
genetics of klinefelter syndroms?
47,XXY or more X chromosomes (less severe)
meiotic nondisjunction
maternal > paternal
weak maternal age effect
clinical features of klinefelter
normal in childhood then get tall stature
most develop normal cognitively
some get malignancy, CV issues, immunogenic
why are microdeletions and microduplications important in clinical genetics?
important cause of cognitive disability, congenital anomalies, genetic variation
what are some uses of FISH
delineate translocations
identify marker chromosomes
detect deletions or duplications
can use in dead/nondividing cells
what are some uses/nonuses for array CGH
can’t see low level mosaicism or balanced rearrangements
autism or pt with unexplained MR
CNV analysis
what is the williams syndrome deletion?
7q11.23
what is the williams syndrome phenotype?
overlyfriendly behavior unusual facial features growth impairment congenital HD (SVAS, elastin arteriopathy) urinary tract abnormalities endocrine issues
genotype-phenotype correlation?
ELN deletion - elastin. SVAS
LIMK1 deletion - lim kinase. visuospatial cognition
what is the deletion in DiGeorge syndrome?
22q11
what is the DiGeorge phenotype?
congenital HD cleft palate hypocalcemia from hypoparathyroidism immune deficincy developmental delay behavioral issues
how common is DiGeorge?
most common microdeletion
What is the Cri du Chat phenotype?
high pitched cry
microcephaly
MR
characteristic facial features
Cri du Chat phenotype?
terminal deletion on chromosome 5p
Cri du Chat genotype-phenotype
fine positional mapping allows for delineation of what deletions lead to what phenotype
what is worse – a large or small pericentric inversion and why
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
