Aneuploidy Type Genetics- Exam Pro Flashcards
Frequency of chromosome anomaly with
live birth
Congenital anomaly with intellectual disability
Congential heart disease
.6%
23%
12%
Frequency and common types of chromosome anomaly in recurrent miscarriage
Balanced translocation
Inversion
Mosaicism
5%
Frequency of chromosome abnormalities in stillbirth and perinatal death
6%
Frequency of chromosome abnormalities in 1st trimester SAB
60% (prior to microarrays - likely lower now)
Autosomal Trisomy (50%) - most common 16
45X 25%
Triploid/tetraploid 20%
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
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
what is the definition of
haploid
diploid
polypoidy
haploid- normal number in gametes n=23
diploid- normal number in zygote n=46
polypoidy -Triploidy/Tetraploid
Down syndrome genetics
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
Medical Problems with T21
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
t21 Liklihood ratio on U/S
Absent nasal bone- 80x
Nuchal fold 11-18x
Echogenic bowel 5x
T18 genetics/prognosis
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
Ultrasound findings t18
CHD FGR Clenched Hands Overlapping Fingers Rockerbottom Feet Renal anomalies
T13 Genetics/prognosis
75% non-disjuction
20 % translocation
5% mosicism
Prognosis:
2.5 % survive to birth
45% die within first month
70% die within first yaer
Ultrasound findings of T13
CHD Holopros Clenched hands Rockerbottom feet polycystic kidneys omphalocele polydactyly Cleft lip/palate
Turner syndrome genetics
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
Ultrasound findings for turners
CHD 30% - aortic
short (SHOX gene)
lymphedema
horseshoe kidney 70%
Clinical: ovrian dysgenesis, ? ID, autoimmune disorders, anxiety
Klinefelters genetic s
47 xxy 80%
- paternal meiosis 1 error 50-60%
mosiac 46 XY/47 XXY 10%
more severe anueuploidy in 10%
Ultrasound findings klinefelters
and associated medical problems
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
Types of structural chromosomal abnormalities
terminal deletion interstital deletion duplication translocation (robertsonian - two acrocentric chromosomes- most common 13:14) pericentric inversion isochromosome ring marker
Translocations risk of abnormal segregation
10-15% (more common in female carriers expecially in robertsonian situations)
- the larger the segment the lower the risk for abnormal offspring
uniparential disomy
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).
Inversions
- paracentric
- pericentric
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.
marker chromosomes
aka derivative chromosome
most common chr 15 or 22 ( cat eye syndrome)
Triploidy gamate genetics
65% dispermy 25% diploid sperm 10 % diploid egg Paternal large placenta, small fetus, partial mole, oligo, CHD Maternal small placenta, large fetus, early loss
Down syndrome screening detection and false positive rate 1st trimester without NB 2nd trimester Integrated Sequential Contingent
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
Marker patterns for T21 T18 Spina Bifida Anencephaly GA>dates SLO/CAH/steroid sulfatase deficiency
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
Cell Free Fetal DNA - detection rate, positive rate, failure rate
- what does it not detect?
DR- 99% Screen positive 0.2% Failure rate 0.3-3% Doesn't detect: unbalanced translocations marker chromosomes microdeletions/duplications triploidy mosaicism
what cuases false positive cell free fetal DNA
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
what causes false negative
low fetal fraction
high BMI
confined placental mosaicism
what to do with no-call results
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)
With NIPT wnl
what isolated findings should be reported as “normal varient”
What findings should not be reported as a soft marker for aneuploidy
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
