Genetics /Fetal Anomalies Flashcards
(142 cards)
1
Q
Taking folate in the periconceptional period for woman with hx of baby with NTD, the risk for recurrence is decreased by approximately what percentage?
A
70%
2
Q
The most common condition to be associated with a cleft palate
A
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.
3
Q
Whats the detection rate of quad test for trisomy 21 and 18?
A
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 %
4
Q
Name the combined screening ?
A
Integrated screening
Sequential screening
5
Q
Whats an integrated screening?
A
NT + PAPP-A + HCG + mAFP + uE3 + DIA.
6
Q
What causes high levels of mAFP greater than 2.5 multiples of the median?
A
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
7
Q
NIPT can’t be done when:
A
1) Moms with wt >90 kg
2) on blood thinners
3) multiple pregnancy
4) uterine anomalies Or fibroids
8
Q
In diagnostic methods methylene blue Cannot be injected because it caused
A
Fetal jejunal atresia
9
Q
After pregnancy with an autosomal trisomy, the risk for any autosomal trisomy in a future pregnancy ?
A
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)
10
Q
— % of non-disjunction that yields to trisomy 21 occurs during ——-, the remaining events during ———.
A
75% of non-disjunction that yields to trisomy 21 occurs during meiosis I, the remaining events during meiosis II.
11
Q
In adult women with Down syndrome —— of their offspring will have Down syndrome .
A
Third
12
Q
Approximately …. of liveborn neonates with Down syndrome are found to have cardiac defects particularly, VSD and endocardial cushion defects.
A
Approximately 1/2 of liveborn neonates with Down syndrome are found to have cardiac defects particularly, VSD and endocardial cushion defects.
13
Q
GI abnormalities identified in —٪ of Down syndrome that’s include ….
A
12%
Include: esophageal atresia, hirschsprung disease, and Deudenal atresia.
14
Q
Characteristics features of Down syndrome:
A
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.
15
Q
Common health problems associated with Down syndrome
A
- Hearing loss 75%
- severs optical refractive errors 50%
- cataracts 15%
- obstructive sleep apnea 60%
- thyroid disease 15%
- higher incidence of leukaemia
16
Q
Prevalence of Trisomy 18
A
Approximately 1 in 2000 pregnancies
17
Q
Prevalence of Down syndrome
A
1 in 500 pregnancies
18
Q
Organ system affected in Edward syndrome
A
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%
19
Q
Among down syndrome cases –% caused by trisomy 21, whereas —% due to robertsonian translocation, remaining—% results from isochromosome or from mosaicism.
A
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.
20
Q
The prevalence of trisomy 13
A
Approximates 1 in 12000 live births, and 1 in 5000 recognized pregnancies
21
Q
Patau syndrome results from trisomy 13 in —%, while remaining from robertsonian translocation
A
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)
22
Q
characteristic findings of patau syndrome are
A
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.
23
Q
DDx of fetus with cephalocele, cystic kidneys, polydactyly
A
Trisomy 13
And autosomal recessive meckel- Gruber syndrom.
24
Q
Aneuploidy and preeclampsia
A
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.
25
The prevalence of Turner syndrome is approximately
1 in 2500 liveborn girls, the missing X chromosome is paternally derived in 80 percent of cases.
26
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.
27
The prevalence of triploidy pregnancies
Approximates 1 in 5000
28
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.
29
Specific markers to detect NTD by amniocentesis (if US in inconclusive)
```
Acetylcholinestrase (more specific)
High AFP ( can be high with any midline defects)
```
30
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)
31
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%)
32
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)
33
Structural Abnormalities associated with Turner syndrome ?
Lt sided cardiac defects(coarctation
34
Physical features of Turner syndrome ?
Features: short stature, broad chest with widely spaced nipples, congenital lymphedema
35
The most common sex chromosome abnormality ? Incidence ?
Klinefelter syndrome, found in approximately 1 in 600 male infants
36
The most common microdeletion and its prevalence
Digeorge from 1 per 4000 to 1 per 7000 births.
37
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.
38
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.
39
The most common robertsonian dislocation is
Der(13;14)(q10;q10) seen in 20% cases of Patau syndrome
40
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
41
What are the types of chromosomal inversions?
Pericentric and paracentric inversions
42
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.
43
Individuals with pericentric inversions are at increased risk for producing offspring with
A duplication/ deletion
44
Those with paracentric inversion at increased risk of
Early pregnancy loss
45
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
46
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
47
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 %
48
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
49
The diagnostic test of choice for NTD
Is targeted sonography (= level II)
50
There are 2 types of aneuploidy screening tests:
- Traditional (analyte-based)
| - cell-free DNA-based
51
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)
```
52
Cystic hygroma confers —-folds increased aneuploidy risk when identified in 1st trimester.
Cystic hygroma confers fivefolds increased aneuploidy risk when identified in 1st trimester.
53
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 %
```
53
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%)
54
What are other significant associations btw serum PAPP-A levels below the 5th percentile?
preterm birth
Growth restrictions
preeclampsia
Fetal demise (similarly low levels of B-hcg associated with fetal demise)
55
When Quad screening test performed?
From 15- 21 wks GA
56
Quad screening test results in Down syndrome
- low msAFP
- high hCG
- low unconjugated estriol
- high dimeric inhibin
57
When Quad screening test performed?
From 15- 21 wks GA
58
Quad screening test results in Down syndrome
- low msAFP
- high hCG
- low unconjugated estriol
- high dimeric inhibin
59
Maternal serum estriol level less than 0.25 MoM has been associated with 2 uncommon but important conditions which are
1) smith-Lemli-Opitz syndrome: AR condition resulting from mutations in 7- dehydrocholestrol reductase gene in chromosome 11. Characterized by abnormalities of CNS, heart, kidneys, syndactly extremities with ambiguous genitalia,FGR.
To confirm dx: elevated amnionic fluid 7-dehyrocholestrol level
2) steroid sulfatase deficiency AKA x-linked ichthyosis May associated with kallmann syndrome, chondrodysplasia punctuate, and/or mental retardation.
Diagnosis test: if male fetus chromosomal microarray analysis or flourescence in situ hybridisation to assess gene locus on x-chromosome May considered
60
Using Integrated test what is the detection rate of Down syndrome ? False positive rate?
94-96% , 5%
61
Recommendations of NIPT (cell-free DNA screening) for high risk for fetal autosomal trisomies those are:
1. Women who will be 35 yrs or older at delivery.
2. A positive 1st or 2nd trimester analyt-based screening test.
3. Sonogram with a minor aneuploidy marker
4. Prior pregnancy with autosomal trisomy
5. Known carriage (patient or pertner) of a balanced robertsonian translocation involving chromosome 21 or 13.
62
Endocardial cushion embryological origin
Neuro crest migration defect of ectoderm
63
Fetal hydantoin syndrome,
also called fetal dilantin syndrome, is a group of defects caused to the developing fetus by exposure to teratogenic effects of phenytoin.
Facial Features: upturned nose, strabismus; ( · ptosis ); and/or epicanthal folds. Mild midfacial hypoplasia· long upper lip with thin vermilion border.
Distal digital hypoplasia- developmental delay
64
Teratogen Anti-fungal
Fluconazole has been associated with pattern of congenital malformations resembling the autosomal resseccive antley-bixler syndrome which includes oral clefts, abnormal facies, and cardiac and skull and long hones and joints abnormalities associated with chronic 1st trimester high doses at 400-800 mg daily.
Low dose debatable!
65
the incidence of congenital hydrocephalus is
Is 1–4.65 for every 10,000 newborns and is the most common neurological diagnosis in children, representing one third of all congenital abnormalities of the nervous system.
(Kutuk MS, Yikilmaz A, Ozgun MT, Dolanbay M, Canpolat M, Uludag S, et al. Prenatal diagnosis and postnatal outcome of fetal intracranial hemorrhage. Childs Nerv Syst 2013;2:257–63.)
66
The presence of ventriculomegaly is possibly diagnosed when the transverse diameter of the cornu occipitale, behind the plexus choroideus, ischial
is >10 mm (normal 6.7±1.12 mm) during the prenatal ultrasound performed during the 12th, 22nd and 32nd week.
67
The presence of isolated SUA is independently associated with
- aneuploidy
- renal anomalies
- an increased risk for IUGR, SGA and very preterm delivery.
(Mariella Mailath-Pokorny et al. Eur J Obstet Gynecol Reprod Biol. 2015 Jan.)
68
Syndromes can be Treated with Growth Hormone :
```
1- Turner Syndrome
2- Noonan Syndrome
3- Laron syndrome
4- Prader-Willi syndrome
5- Silver-Russell syndrome
```
69
The cell generation time is
the time required to complete the five phases of the cell cycle
70
The G1 phase (G = gap) involves
various cellular activities, such as protein synthesis, RNA synthesis, and DNA repair.
71
When G1 prolonged the cell is considered to be in
the G0 phase (the resting phase)
72
Kartagener syndrome called to which gynecological problems
is an autosomal recessive and a type of primary ciliary dyskinesia that is also characterized by situs inversus totalis.
Can led to Recurrent respiratory infections and infertility( and if pregnancy happen Can be ectopic pregnancy)
73
Duchenne muscle dystrophy is
X -linked recessive
74
Initiating codon for protein synthesis :
AUG
75
The window for testing using the combined test is
11 weeks + 2 days and 14 weeks + 1 day of pregnancy.
76
The window for testing using the quadruple test is
14 weeks+ 2 days to 20 weeks + 0 days gestation
77
BRCA gene mutations account for around ---% of inherited breast cancers
Around 1 in 20 (5%) of people diagnosed with breast cancer will have a BRCA 1 and BRCA 2 mutation. They account for 25% of inherited breast cancers. Men with a BRCA mutation are at increased risk with a lifetime risk of breast cancer of 1-7%.
78
inherited cases of pheochromocytoma may be associated with a genetic condition
Multiple Endocrine Neoplasia Types 2a and 2b, Von Hippel-Lindau Syndrome, and Neurofibromatosis type 1, paraganglioma syndrome type 3
79
Cardiac anomalies (ductal dependent lesions) -which means that PDA is crucial for their survival
- hypoplastic Left heart syndrome
- mitral stenosis
- aortic stenosis
- aortic coarctation.
80
Time of Antenatal screening and diagnostic tests
81
Marfan syndrome mode of inheritance
Autosomal dominant
82
Duchenne muscular dystrophy mode of inheritance
X-linked recessive
83
Gray baby syndrome is a condition in which an infant experiences a life-threatening reaction to which antibiotic
Chloramphenicol
84
Most specific cardiac anomalies to baby of diabetic mother
TGA
85
What is the teratogenecity that related to ACE inhibitors ?
ACE inhibitors cause renal failure in neonates, decreased skull ossification and renal tubular dysgenesis.
Further reading Collins S, Arulkumaran S, et al. Oxford Handbook of Obstetrics & Gynaecology. 3rd ed. Oxford: Oxford University Press; 2013.
86
The first branchial arch develops structures called the maxillary and mandibular prominences, which ultimately form the skeleton, skin, muscles, and other structures of the upper (maxilla) and lower (mandible) jaws. In the center of the upper face, a structure called the frontonasal prominence, which is separate from the branchial arches, forms, among other things, the nostrils and the philtrum. The medial maxillary prominences fuse with the frontonasal prominence during this time. Failure of this process results in
cleft lip.
87
Failure of fusion of the palatine prominences (derived from The first pharyngeal arch)causes
cleft palate
88
Fetus with NTD, What is the recurrence risk in a subsequent pregnancy if mother does not take periconceptional folic acid?
3-5 %
89
What additional ultrasound measurement should be taken in the same image that the cerebellum and cisterna magna are evaluated?
Nuchal fold
90
What other sonographic findings may be seen with NTD?
a. Ventriculomegaly
b. Scalloping of the frontal bones
c. Effacement of the cisterna magna
91
What is the upper limit of normal after 15 weeks’ gestation for the lateral ventricle?
10 mm
92
What condition should be suspected when a “teardrop” shaped lateral ventricle is seen on prenatal sonography?
Agenesis of the corpus callosum
93
Which of the following is of prognostic significance in the evaluation of congenital diaphragmatic hernias?
- Degree of liver herniation in the chest
- Sonographic lung-to-head measurement
- Magnetic resonance imaging of lung volumes
94
indications for fetal echocardiographic evaluation?
- Maternal phenylketonuria
- Fetal arrhythmia heard on Doppler
- Paternal history of ventricular septal defect
95
If cushing defect or AVSD is present on an ultrasound performed at 24 weeks’ gestation. What is the likelihood this fetus has trisomy 21?
50%
96
If the measurement of the renal pelvis in Fetal US is 16 mm, what is the likelihood that a postnatal abnormality will be diagnosed?
90%
97
What is a normal S/D ratio after 30 weeks’ gestation?
2.0
98
Uterine blood flow is estimated to rise from -- mL/min early in gestation to --- to --- mL/min by term
Uterine blood flow is estimated to rise from 50 mL/min early in gestation to 500 to 750 mL/min by term
99
The S/D ratio approximates ≤-- after 20 weeks’ gestation, <-- after 30 weeks’, and close to -- at term.
The S/D ratio approximates ≤4.0 after 20 weeks’ gestation, <3.0 after 30 weeks’, and close to 2.0 at term.
100
versal of enddiastolic flow has been associated with greater than ---percent obliteration of the small muscular arteries in placental tertiary stem villi (Kingdom, 1997; Morrow, 1989).
versal of enddiastolic flow has been associated with greater than 70-percent obliteration of the small muscular arteries in placental tertiary stem villi (Kingdom, 1997; Morrow, 1989).
101
The incidence of neural-tube defects (NTDs) is
0.9 per 1000 live births
102
the 677C → T substitution in the gene that encodes methylene tetrahydrofolate reductase associated with which Birth defect
Neural-Tube Defects
103
preconceptional folic acid therapy significantly reduced the risk for a recurrent NTD by -- percent
72 percent
104
all women who may become pregnant are recommended to take daily --- to -- μg of folic acid orally before conception and through the first trimester
all women who may become pregnant are recommended to take daily 400 to 800 μg of folic acid orally before conception and through the first trimester
105
In mothers with phenylketonuria, the phenylalanine concentration is ideally brought into normal range -- months before conception and then maintained there throughout pregnancy (American College of Obstetricians and Gynecologists, 2020a).
the phenylalanine concentration is ideally brought into normal range 3 months before conception and then maintained there throughout pregnancy (American College of Obstetricians and Gynecologists, 2020a).
106
In mothers with phenylketonuria, The target phenylalanine blood concentration is --- to --- µmol/L (Camp, 2014).
The target phenylalanine blood concentration is 120 to 360 µmol/L (Camp, 2014).
107
When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is -- to -- percent
When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is 3 to 5 percent
108
Between 15 and 20 weeks’ gestation, an upper MSAFP threshold of 2.5 multiples of the median (MoM) is anticipated to detect -- percent with fetal anencephaly and -- percent with myelomeningocele.
Between 15 and 20 weeks’ gestation, an upper MSAFP threshold of 2.5 multiples of the median (MoM) is anticipated to detect 95 percent with fetal anencephaly and 80 percent with myelomeningocele.
109
Meckel-Gruber syndrome mode of inheritance, features
Cephalocele is an important feature of the autosomal recessive Meckel-Gruber syndrome, which includes cystic renal dysplasia and polydactyly. A cephalocele not located in the occipital midline raises suspicion for amnionic-band sequence
110
Detection of spina bifida is aided by two characteristic cranial findings which are ----
Flatting or scalloping of the frontal bones is termed the “lemon sign,” and anterior curvature of the cerebellum with effacement of the cisterna magna is the “banana sign”, These findings are manifestations of the Arnold-Chiari or Chiari II malformation. This develops when downward displacement of the spinal cord pulls a portion of the cerebellum through the foramen magnum and into the upper cervical canal. The biparietal diameter measurement often lags behind the other biometric parameters. Ventriculomegaly is common after mid-gestation, and 80 to 90 percent of infants with myelomeningocele require ventriculoperitoneal shunt placement
111
Mild ventriculomegaly is diagnosed when the atrial width measures -- to -- mm; moderate ventriculomegaly, when the measurement is -- to -- mm; and severe ventriculomegaly when >-- mm (Society for Maternal-Fetal Medicine, 2018).
Mild ventriculomegaly is diagnosed when the atrial width measures 10 to 12 mm; moderate ventriculomegaly, when the measurement is 13 to 15 mm; and severe ventriculomegaly when >15 mm (Society for Maternal-Fetal Medicine, 2018).
112
agenesis of the corpus callosum incidence, association
occurs in 1 in 4000 to 5000 pregnancies (Ballardini, 2018; Stoll, 2019; Szabo, 2011). It is associated with other anomalies, aneuploidy, and more than 200 genetic syndromes. Thus, chromosomal microarray analysis should be offered, and genetic counseling can be challenging. In a review of apparently isolated cases, fetal MR imaging identified additional brain abnormalities in more than 20 percent of cases (Sotiriadis, 2012). If MR imaging does not identify associated abnormalities, normal developmental outcome in 67 to 75 percent of cases and severe disability in about 10 percent has been reported (des Portes, 2018; Sotiriadis, 2012).
113
Holoprosencephaly pathogenesis , association
During early normal brain development, the prosencephalon or forebrain divides as it becomes the telencephalon and diencephalon. With holoprosencephaly, the prosencephalon fails to divide completely into two separate cerebral hemispheres and underlying paired diencephalic structures.
of trisomy 13 cases, two thirds are found to have holoprosencephaly.
114
The most severe form, alobar holoprosencephaly, is characterized by
single monoventricle that surrounds fused thalami
115
Dandy-Walker Malformation
This posterior fossa abnormality is characterized by agenesis of the cerebellar vermis, posterior fossa enlargement, and elevation of the tentorium cerebelli.
116
Caudal regression is associated with genitourinary malformations and syndromes such as the
VACTERL association ( Vertebral defects, Anal atresia,Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities)
117
The prevalence of non-immune hydrops approximates - case per ---- second-trimester pregnancies
The prevalence of non-immune hydrops approximates 1 case per 1500 second-trimester pregnancies
118
Good prognostic factor in diaphragmatic hernia is
Lung/head ratio more than 1
119
If a woman is a carrier for a balanced translocation that includes chromosome 21, then each of her children has about a 1 in — or —% chance for ending up with Down syndrome. If a man is a carrier, this falls to around 3 in — or —%.
If a woman is a carrier for a balanced translocation that includes chromosome 21, then each of her children has about a 1 in 8 or 12% chance for ending up with Down syndrome. If a man is a carrier, this falls to around 3 in 100 or 3%.
120
first-trimester aneuploidy screen with a sensitivity for trisomy 21? the false-negative rate ? PPV ? NPV?
first-trimester aneuploidy screen with a sensitivity of 80 percent for trisomy 21, the false-negative rate is 20 percent, so the test is anticipated to miss 1 in 5 affected pregnancies. PPV 5% (PPV is directly affected by disease prevalence, it is higher in women aged 35 years and older than in younger women), Negative predictive value is the proportion of those with a negative screening test result who have unaffected (euploid) fetuses. Because the prevalence of aneuploidy is low, the negative predictive value of all aneuploidy screening tests generally exceeds 99 percent.
121
When Cell-free DNA Screening can be performed?
CfDNA screening can be performed at any time after 9 to 10 weeks’ gestation.
122
What is the sensitivity / specificity of Cell-free DNA Screening as aneuploidy screening test.
In a metaanalysis of 35 studies of largely high-risk pregnancies, the pooled sensitivity to detect trisomy 21 was 99.7 percent, and for trisomies 18 and 13, 98 percent and 99 percent, respectively (Gil, 2017) For each of these autosomal trisomies, the specificity is 99.9 percent, and the combined false-positive rate is less than 0.2 percent.
123
If cfDNA is used as a secondary screening test and yields a negative result, the residual risk for a chromosomal abnormality may be as high as -- percent
If cfDNA is used as a secondary screening test and yields a negative result, the residual risk for a chromosomal abnormality may be as high as 2 percent
124
Limitations of cfDNA Screening
In 2 to 4 percent of pregnancies screened with cfDNA, no result is obtained. These cases are termed “no-call,” or indeterminate. With a no-call result, the fetal aneuploidy risk is as high as 4 percent
125
Quad screening results of Pregnancies with fetal trisomy 21 /18 are characterized by
lower MSAFP, higher hCG, lower unconjugated estriol, and higher dimeric inhibin levels.
In cases of trisomy 18, levels of MSAFP, hCG, and unconjugated estriol are all decreased, and inhibin is not part of the calculation.
126
Using an MSAFP level of 2.5 MoM as the upper limit of normal, the neural-tube defect detection rate approximates -- percent for anencephaly and -- percent for spina bifida, with a screen-positive rate of - to - percent (American College of Obstetricians and Gynecologists, 2019c; Palomaki, 2019).
Using an MSAFP level of 2.5 MoM as the upper limit of normal, the neural-tube defect detection rate approximates 95 percent for anencephaly and 80 percent for spina bifida, with a screen-positive rate of 1 to 3 percent (American College of Obstetricians and Gynecologists, 2019c; Palomaki, 2019).
127
The nuchal fold is considered thickened if it measures ≥- mm at -- to -- week This finding is seen in approximately 1 per 200 pregnancies and confers more than ---fold risk for trisomy 21
The nuchal fold is considered thickened if it measures ≥6 mm at 15 to 20 week This finding is seen in approximately 1 per 200 pregnancies and confers more than tenfold risk for trisomy 21
128
An echogenic intracardiac focus is a focal papillary muscle calcification that is neither a structural nor functional cardiac abnormality. It is present in -- to -- percent of normal fetuses.
An echogenic intracardiac focus is a focal papillary muscle calcification that is neither a structural nor functional cardiac abnormality. It is present in 4 to 7 percent of normal fetuses.
129
various thresholds have been defined, the pelvis is typically considered dilated if it exceeds -- mm in the second trimester or -- mm at approximately 32 weeks’ gestation (Nguyen, 2014; Reddy, 2014). The second-trimester threshold is used to identify pregnancies that warrant subsequent third-trimester evaluation.
various thresholds have been defined, the pelvis is typically considered dilated if it exceeds 4 mm in the second trimester or 7 mm at approximately 32 weeks’ gestation (Nguyen, 2014; Reddy, 2014). The second-trimester threshold is used to identify pregnancies that warrant subsequent third-trimester evaluation.
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With Echogenic fetal bowel it is identified in approximately --- percent of pregnancies and The fetal trisomy 21 risk is increased approximately --fold.
With Echogenic fetal bowel it is identified in approximately 0.5 percent of pregnancies and The fetal trisomy 21 risk is increased approximately sixfold.
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The nasal bone is measured between -- and -- weeks’ gestation. Hypoplasia may be defined as shorter than --- mm, as >- standard deviations below the mean, or based on a ratio to the biparietal diameter (Cicero, 2003).
The nasal bone is measured between 15 and 22 weeks’ gestation. Hypoplasia may be defined as shorter than 2.5 mm, as >2 standard deviations below the mean, or based on a ratio to the biparietal diameter (Cicero, 2003).
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Cystic Fibrosis mutated gene name, location,
This disorder is caused by a mutation in the cystic fibrosis conductance transmembrane regulator (CFTR) gene, which is located on the long arm of chromosome 7 and encodes a chloride-channel protein. the American College of Obstetricians and Gynecologists (2020a) has recommended that all women who are pregnant or considering pregnancy be offered CF carrier screening.
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MTX embryopathy
craniofacial and skeletal abnormalities and fetal-growth restriction
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risk of down syndrome in duodenal atresia
Twenty-five to 30% of cases of duodenal atresia occur in babies with Down's syndrome
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What is the risk of down syndrome if the father is with balanced translocation and the mother is normal:
3% - 4.5%
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Estimated Risks for Fetal Trisomy 21 and Any Aneuploidy According to Maternal Age and Timing of Diagnosis
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the Society for Maternal–Fetal Medicine recommends that cell-free DNA testing be lim- ited to women at increased risk of fetal aneuploidy, such as patients with one of the following conditions:
• Advanced maternal age
• Fetal ultrasound findings concerning for aneuploidy
• History of pregnancy with trisomy 21, trisomy 18, or
trisomy 13
• Positive screening tests for aneuploidy
• Known parental balanced Robertsonian translocation
with risk of trisomy 13 or trisomy 21
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the prevalence of trisomy 21 in the screened population of Cell-free DNA screening tests
the prevalence of trisomy 21 in the screened population greatly affects the positive predictive value (PPV) (ie, percentage that a positive test is a true result). In a high-risk population screened by age, history of a pregnancy with trisomy 21, abnormal ultrasound find- ings, abnormal genetic screening, or known parental Robertsonian balanced translocation, the PPV of a cell- free DNA screen for trisomy 21 is 87%. In the general obstetric population (who have an a priori risk of 1:2,500), however, the same test result carries a PPV of only 33%.
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