Genetics /Fetal Anomalies Flashcards
Taking folate in the periconceptional period for woman with hx of baby with NTD, the risk for recurrence is decreased by approximately what percentage?
70%
The most common condition to be associated with a cleft palate
is Pierre-Robin Sequence (PRS). PRS is usually detected at birth because these babies can be born with an unusually small chin. These babies usually have a cleft palate because the tongue does not fall into place properly while the baby is developing. The cleft is usually wide and U-shaped and will affect the hard palate at the front of the mouth and the soft palate at the back.
Whats the detection rate of quad test for trisomy 21 and 18?
Both trisomies have same detection rate 75% for women younger than 35 yo. 90% for women whose older than 35 yo.
In general detection rate reaches 81-83%
With screen positive rate 5%
Trisomy 18 false positive 0.5 %
Name the combined screening ?
Integrated screening
Sequential screening
Whats an integrated screening?
NT + PAPP-A + HCG + mAFP + uE3 + DIA.
What causes high levels of mAFP greater than 2.5 multiples of the median?
Open NTD Abdominal wall defects (omphalocele, Gastroschiasis) Esophageal or intestinal obstruction Liver necrosis Renal anomalies(PCKD,agenesis, nephrosis,obstruction) Cloacal extrophy Cystic hygroma Sacrococcygeal Teratomas Congenital skin abnormalities Pilonidal cyst Osteogenesis imperfecta Multiple gestation Oligohydramnios FGR Incorrect pregnancy dating/underestimated GA Fetal death Chorioangioma of placenta Placenta intervillous thrombosis Placental abruption Preeclampsia Maternal hepatoma or teratoma
NIPT can’t be done when:
1) Moms with wt >90 kg
2) on blood thinners
3) multiple pregnancy
4) uterine anomalies Or fibroids
In diagnostic methods methylene blue Cannot be injected because it caused
Fetal jejunal atresia
After pregnancy with an autosomal trisomy, the risk for any autosomal trisomy in a future pregnancy ?
Approximates 1% until the woman’s age-related risk exceeds this.
( prenatal diagnosis with CVS or amniocentesis is offered in these subsequent pregnancies, prenatal chromosomal studies not indicated unless the affected pregnancy was caused by an unbalanced translocation or other structural rearrangement)
— % of non-disjunction that yields to trisomy 21 occurs during ——-, the remaining events during ———.
75% of non-disjunction that yields to trisomy 21 occurs during meiosis I, the remaining events during meiosis II.
In adult women with Down syndrome —— of their offspring will have Down syndrome .
Third
Approximately …. of liveborn neonates with Down syndrome are found to have cardiac defects particularly, VSD and endocardial cushion defects.
Approximately 1/2 of liveborn neonates with Down syndrome are found to have cardiac defects particularly, VSD and endocardial cushion defects.
GI abnormalities identified in —٪ of Down syndrome that’s include ….
12%
Include: esophageal atresia, hirschsprung disease, and Deudenal atresia.
Characteristics features of Down syndrome:
Brachycephaly
Epicanthal folds
Up-slanting palpebral fissures
Brushfield spots (greyish spot on the periphery of the iris)
Flat nasal bridge, hypotonia, redundant Nuchal tissue, short fingers, single palmar crease, hypoplasia of the middle phalanx of the fifth finger, sandal-toe gap” btw 1st and 2nd toes.
Common health problems associated with Down syndrome
- Hearing loss 75%
- severs optical refractive errors 50%
- cataracts 15%
- obstructive sleep apnea 60%
- thyroid disease 15%
- higher incidence of leukaemia
Prevalence of Trisomy 18
Approximately 1 in 2000 pregnancies
Prevalence of Down syndrome
1 in 500 pregnancies
Organ system affected in Edward syndrome
Heart defect(90%): VSD.
Cerebral vermian agenesis, myelomeningocele, diaphragmatic hernia, omphalocele, imperforate anus, renal anomalies such as horseshoe kidney, prominent occiput, posteriorly rotated and malformed ears, micrognathia, clenched hands with overlapping digits, radial aplasia with hyperflexion of the wrists and rockerbottom or clubbed feet.
Strawberry-shaped cranium (40٪)
Wide cavum septum pellucidum (more than 90%)
Choroid plexus cyst in more than 50%
Among down syndrome cases –% caused by trisomy 21, whereas —% due to robertsonian translocation, remaining—% results from isochromosome or from mosaicism.
Among down syndrome cases 95% caused by trisomy 21, whereas 3-4% due to robertsonian translocation, remremaining 1-2% results from isochromosome or from mosaicism.
The prevalence of trisomy 13
Approximates 1 in 12000 live births, and 1 in 5000 recognized pregnancies
Patau syndrome results from trisomy 13 in —%, while remaining from robertsonian translocation
Patau syndrome results from trisomy 13 in 80%, while remaining from robertsonian translocation.
(Most frequent structural chromosomal rearrangement is a translocation btw chromosome 13 and 14)
characteristic findings of patau syndrome are
Defects (present in 2/3 of cases) May accompanied by microcephaly, hypotelorism, and nasal abnormalities(proboscis), cardiac defects in 90% of cases, NTD- cephalocele, microphthalmia, cleft lip-palate, omphalocele, cystic renal dysplasia, polydactyly, rockerbottom feet, areas of skin aplasia.
DDx of fetus with cephalocele, cystic kidneys, polydactyly
Trisomy 13
And autosomal recessive meckel- Gruber syndrom.
Aneuploidy and preeclampsia
Unlike other aneuploidies, fetal trisomy 13 confers risk to the pregnant woman,hyperplacentosis and preeclampsia develop in up to half of pregnancies with trisomy 13 carried beyond the 2nd trimester.
The prevalence of Turner syndrome is approximately
1 in 2500 liveborn girls, the missing X chromosome is paternally derived in 80 percent of cases.
Polyploidy (Triploidy) types:
Type I triploidy (diandric triploidy)
Extra paternal chromosomes from fertilization of one egg by two sperms or by single abnormal diploid sperm, produces partial molar pregnancy.
Type II digynic triploidy extra chromosomes is maternal where egg fails to undergo 1st or 2nd meiotic division before fertilization didn’t develop molar changes but fetus displays asymmetrical growth restriction.
The prevalence of triploidy pregnancies
Approximates 1 in 5000
Recurrence risk of a woman whose triploid fetus survived past the 1st trimester is
1 to 1.5 % (thus prenatal diagnosis is offered in future pregnancies.
Specific markers to detect NTD by amniocentesis (if US in inconclusive)
Acetylcholinestrase (more specific) High AFP ( can be high with any midline defects)
Omphalocele has higher genetic abnormalities association than gastroschiasis, how to differentiate btw them?
An omphalocele is a protrusion of abdominal viscera from a midline defect at the base of the umbilicus, covered by a thin membrane (Immediate dangers are drying of the viscera, hypothermia and dehydration due to evaporation of water from the exposed viscera, and infection of the peritoneal surfaces)
Incidence of Omphalocele, and incidence of associated anomalies? Give examples
The estimated incidence is 1 in 3000 to 5000 live births. Infants with omphalocele have a very high incidence of other congenital anomalies (up to 70%)
Among the 1 percent or less that survived from pregnancies with Turner syndrome and yield a liveborn neonate, what is the percentage of monosomy x ? And mosaicism ?
only have of these actually have monosomy X, 1/4 have mosaicism, such as and another 15 % have isochromosome X, that is 46 X,I (Xq)
Structural Abnormalities associated with Turner syndrome ?
Lt sided cardiac defects(coarctation
Physical features of Turner syndrome ?
Features: short stature, broad chest with widely spaced nipples, congenital lymphedema
The most common sex chromosome abnormality ? Incidence ?
Klinefelter syndrome, found in approximately 1 in 600 male infants
The most common microdeletion and its prevalence
Digeorge from 1 per 4000 to 1 per 7000 births.
What are the types of Chromosomal translocation ?
1- Reciprocal (prevalence 1 in 600 birth) risk of major structural or developmental abnormality is 6%
2- robertsonian (these involve only acrocentric chromosomes, which are chromosomes 13,14,15,21 and 22. Those have extremely short p arms) this translocation found in 1 in 1000 individuals. Its incidence of abnormal offspring approximates 15% if carried by mother and 2% if carried by father.
Translocation carriers identified after the birth of an abnormal child have .. to .. % risk of producing liveborn offspring with unbalanced translocation, while carriers identified for other reasons (e.g. infertility w/u) have only ..% risk.
Translocation carriers identified after the birth of an abnormal child have 5 to 30 % risk of producing liveborn offspring with unbalanced translocation, while carriers identified for other reasons (e.g. infertility w/u) have only 5% risk.
The most common robertsonian dislocation is
Der(13;14)(q10;q10) seen in 20% cases of Patau syndrome
The most common isochromosome
Which involves the long arm of the X chromosome, i(Xq), which is the etiology of 15% of Turner syndrome cases
What are the types of chromosomal inversions?
Pericentric and paracentric inversions
The observed risk of abnormal offspring in a pericentric inversion carrier is —— after ascertainment was made after the birth of abnormal child.
5-10 % , but the risk is 1-3 % if genetic test prompted by other indication (other than previous hx of abnormal child)
An important exception is pericentric inversion on ch9 (inv(9)(p11q12) which considered a normal variant in 1% of population.
Individuals with pericentric inversions are at increased risk for producing offspring with
A duplication/ deletion
Those with paracentric inversion at increased risk of
Early pregnancy loss
Although outcomes with confined placental mosaicism are generally good, what are the possible complications that can rise with it
FGR is more common, and the stillbirth risk is also higher
Paternal age older than 40 is associated with increased risk for spontaneous genetic mutations in particular…..
Single base substitutions may result in offspring with new autosomal dominant disorders or x-linked carrier state (craniosyntosis syndromes
The overall sensitivity of amniocentesis to diagnose open NTD approximates …% with a false positive rate of … %
The overall sensitivity of amniocentesis to diagnose open NTD approximates 98% with a false positive rate of 0.4 %
Elevated amniotic fluid fluid AFP levels and positive assay results for acetylcholinestrase can be found in fetal abnormalities like
Ventral wall defects, esophageal atresia, fetal teratoma, cloacal atresia
The diagnostic test of choice for NTD
Is targeted sonography (= level II)
There are 2 types of aneuploidy screening tests:
- Traditional (analyte-based)
- cell-free DNA-based
Combined 1st trimester screening test composed of
Two maternal serum analytes: - HCG ( increased in down syn) - PAPP-A (Both decreased in trisomy 18 and 13) With Nuchal translucency (btw 11-14 wks GA)
Cystic hygroma confers —-folds increased aneuploidy risk when identified in 1st trimester.
Cystic hygroma confers fivefolds increased aneuploidy risk when identified in 1st trimester.
First trimester screening efficacy ( detection rate % + false positive)
False positive 5% Detection rate for: Trisomy 21 approximates 80% Trisomy 18 80% Trisomy 13 50% Maternal age affects (detection rate 67 to 75% in women younger than 35 yrs at delivery and reaches 90-95% in women older than 35yrs with higher false positive of 15-22 %
NT as an isolated marker
Efficacy
(Detection rate + false positive rate)
False positive rate 5%
NT can detects 2/3 of Down syndrome around 80% (The combination of NT and maternal serum free β-hCG and PAPP-A improves the detection to 90%)