Aneuploidy Type Genetics- Exam Pro

Question 1

Frequency of chromosome anomaly with
live birth
Congenital anomaly with intellectual disability
Congential heart disease

Answer 1

.6%
23%
12%

Question 2

Frequency and common types of chromosome anomaly in recurrent miscarriage

Answer 2

Balanced translocation
Inversion
Mosaicism
5%

Question 3

Frequency of chromosome abnormalities in stillbirth and perinatal death

Answer 3

6%

Question 4

Frequency of chromosome abnormalities in 1st trimester SAB

Answer 4

60% (prior to microarrays - likely lower now)
Autosomal Trisomy (50%) - most common 16
45X 25%
Triploid/tetraploid 20%

Question 5

Rates of chromosomal anomalies in the newborn
Pericentric Inversion
Balanced Translocation 
Trisomy 21
47 XXY
47 XYY
47 XXX
Unbalanced Translocation
Trisomy 18
45 x
Trisomy 13

Answer 5

Pericentric Inversion- 1:100
Balanced Translocation 1:500
Trisomy 21 1:700
47 XXY 1:1000 MALES
47 XYY 1:1000 MALES
47 XXX 1:1000 FEMALES
Unbalanced Translocation 1:2000
Trisomy 18 1: 6000
45 x 1: 5000 FEMALES
Trisomy 13 1:10,000

Question 6

what is the definition of
haploid
diploid
polypoidy

Answer 6

haploid- normal number in gametes n=23
diploid- normal number in zygote n=46
polypoidy -Triploidy/Tetraploid

Question 7

Down syndrome genetics

Answer 7

95% denovo
75% M 1 error 
25% M 2 error 
3% Robertsonian translocation 
2% mosaicism 
Only 25% survive to term 
5% of all spontanous abortions

Question 8

Medical Problems with T21

Answer 8

CHD 40%
GI anomaly 15%
congenital myeloproliferative syndrome 10%
cataracts/hearing loss/ thyroid dysfunction/ dental/ alantoaxial instability/hirschsprung/short/ developmental delay/intellectual disability/seizures/lukemia/celiac/ OSA

Question 9

t21 Liklihood ratio on U/S

Answer 9

Absent nasal bone- 80x
Nuchal fold 11-18x
Echogenic bowel 5x

Question 10

T18 genetics/prognosis

Answer 10

90% nondisjuction - 70% M 2
10 % mosiacism
1 % translocation

5% survive to birth
50% die in first week
90% die in first year
- central apnea, seizures, pneumonia

Question 11

Ultrasound findings t18

Answer 11

CHD
FGR
Clenched Hands
Overlapping Fingers
Rockerbottom Feet
Renal anomalies

Question 12

T13 Genetics/prognosis

Answer 12

75% non-disjuction
20 % translocation
5% mosicism

Prognosis:
2.5 % survive to birth
45% die within first month
70% die within first yaer

Question 13

Ultrasound findings of T13

Answer 13

CHD
Holopros
Clenched hands
Rockerbottom feet
polycystic kidneys
omphalocele
polydactyly
Cleft lip/palate

Question 14

Turner syndrome genetics

Answer 14

45 x in 50-60%
mosiac with 46 xx in 10-15%
mosiac with other combos including 46 xy in 25%
- gonadectomy with xy mosiacism

Question 15

Ultrasound findings for turners

Answer 15

CHD 30% - aortic
short (SHOX gene)
lymphedema
horseshoe kidney 70%

Clinical: ovrian dysgenesis, ? ID, autoimmune disorders, anxiety

Question 16

Klinefelters genetic s

Answer 16

47 xxy 80%
- paternal meiosis 1 error 50-60%
mosiac 46 XY/47 XXY 10%
more severe anueuploidy in 10%

Question 17

Ultrasound findings klinefelters

and associated medical problems

Answer 17

18%  will have congnetial anomalies
cleft lip 
inguinal hernia  
cardiac malformations
clinodactylyl (5th finder)
hypospadius
cryptorchidism 
gynecomastia 
expressive language delay
auditory processing disability 
tremor
scoliosis
autoimmune 
germ cell tumors
Increased risk for BRCA  
infertility

Question 18

Types of structural chromosomal abnormalities

Answer 18

terminal deletion 
interstital deletion 
duplication 
translocation  (robertsonian - two acrocentric chromosomes- most common 13:14)
pericentric inversion 
isochromosome 
ring 
marker

Question 19

Translocations risk of abnormal segregation

Answer 19

10-15% (more common in female carriers expecially in robertsonian situations)
- the larger the segment the lower the risk for abnormal offspring

Question 20

uniparential disomy

Answer 20

trisomy rescue, or monosomy rescue
UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent (an earlier stage meiosis I error) or isodisomy, in which a single chromosome from one parent is duplicated (a later stage meiosis II error).

Question 21

Inversions

• paracentric
• pericentric

Answer 21

paracentric no centramere involved
- lower risk for abnormal offspring
pericentric includes the centramere 
- higher risk for abnormal offspring 
- bigger inversion increases the risk for unbalanced offspring.

Question 22

marker chromosomes

Answer 22

aka derivative chromosome

most common chr 15 or 22 ( cat eye syndrome)

Question 23

Triploidy gamate genetics

Answer 23

65% dispermy
25% diploid sperm 
10 % diploid egg
Paternal 
large placenta, small fetus, partial mole, oligo, CHD
Maternal  
small placenta, large fetus, early loss

Question 24

Down syndrome screening detection and false positive rate 
1st trimester without NB
2nd trimester
Integrated
Sequential 
Contingent

Answer 24

1st trimester without NB 86/4
2nd trimester 82/7
Integrated 93/3
Sequential 95
Contingent 88-94

PPV for most >80%, Integrated/sequential/contingent >90

Question 25

Marker patterns for 
T21
T18 
Spina Bifida
Anencephaly 
GA>dates
SLO/CAH/steroid sulfatase deficiency

Answer 25

T21 - low msAFP, high hCG, Low uE2, High inhibin
T18- low msAFP, hCG, uE2, Inhibin
SB- high msAFP
Anecephaly- High AFP, and low E2
GA>Dates high AFP, low hCG, High E2, High inhibin
SLO/CAH/steroid sulfatase- very low E2

Question 26

Cell Free Fetal DNA - detection rate, positive rate, failure rate
- what does it not detect?

Answer 26

DR- 99%
Screen positive 0.2%
Failure rate 0.3-3%
Doesn't detect:
unbalanced translocations 
marker chromosomes 
microdeletions/duplications
triploidy 
mosaicism

Question 27

what cuases false positive cell free fetal DNA

Answer 27

confined placental mosaicism
vanishing twin 
maternal cancer (35% of women with >2 aneuploidies and a normal fetus)
Maternal mosaicism 
Maternal copy number variant 
Maternal Sex chromosome anuploidy
Vit B12 deficiency
autoimmune disorder
intrahepatic cholestasis of pregnancy
Fibroids
Transplant

Question 28

what causes false negative

Answer 28

low fetal fraction
high BMI
confined placental mosaicism

Question 29

what to do with no-call results

Answer 29

low fetal fraction- high false negative 
can be due to :
early gestational age
high BMI- 20% >250 lb, 50% >350 lb 
Aneuploidy - rate as high as 20% (including triploidy)

Question 30

With NIPT wnl
what isolated findings should be reported as “normal varient”
What findings should not be reported as a soft marker for aneuploidy

Answer 30

normal- EIF, CPC, Sandal Gap, Clinodactyly
Not a soft marker- pyelectasis, SUA, Ventriculomegaly, Echogenic bowel, Thick nuchal fold, Hypoplastic nasal bone, shortened humerus or femur