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2022 - MFM ORAL BOARDS ALL > Genetics > Flashcards

Genetics Flashcards

1
Q

What testing is recommended for all people?

A

Aneuploidy screening, CF, SMA

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2
Q

What are the components of a first trimester screen?

A

PAPP-A
Free B-hCG
AFP
Nuchal translucency

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3
Q

What is the technique for an NT scan?

A 
Margins of NT clear
Fetus in mid-sagittal plane
Fetus occupies majority of image
Fetal head in neutral position
Fetus observed away from amnion
Calipers used
Horzontal crossbars placed correctly (perpendicular to long axis)
Measurement at widest NT space 
Measure 3x and report largest measurement
CRL 45-84mm
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4
Q

Differential diagnosis for NT of 4.0mm

A 
Chromosomal malformations (aneuploidy)
Structural malformations (heart, skeletal dysplasia)
Other genetic syndromes (noonans, SLOS)
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5
Q

How do you counsel a patient with a thickened NT?

A 
Increased risk of:
genetic disorders
structural malformations
miscarriage
fetal demise
If genetic testing, echo, and anatomy are normal, then 95% will have a normal outcome
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6
Q

What would you offer a patient with an NT of 4.0mm?

A

Invasive testing (karyotype / microarray)
Noonans
Targeted early anatomy
….

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7
Q

In patients with a thickened NT, but normal karyotype/array/noonan, normal anatomy and normal fetal echo. What is the likelihood of a normal outcome?

A

95%

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8
Q

How do you counsel a patient about prenatal genetic testing options?

A

Serum screening is non diagnostic and can have both false positives and false negatives
Women who desire definitive information about chromosomal conditions in their pregnancy should be offered the option of amniocentesis or CVS.

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9
Q

In your practice, for whom do you recommend cell free DNA screening?

A

All patients

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10
Q

How do you counsel the low risk patient who desires cell free DNA screening?

A

cfDNA is a screening test, and both false positive and false negative results occur.
This is particularly true in lower risk women, in whom a positive test is more likely to be a false positive.
Women who desire definitive information about chromosomal conditions in their pregnancy should be offered the option of amniocentesis or CVS.

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11
Q

What is sensitivity of cell free DNA for T21?
What is the sensitivity of cf DNA for T18?
T13?

A

T21: 99%
T18: 97%
T13: 97%

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12
Q

For a 35 yo, What is PPV of cell free DNA for T21?
T18?
T13?

A

80%
40%
20%

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13
Q

For a 35 yo, What is NPV of cell free DNA for T21?
T18?
T13?

A

> 99% for all

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14
Q

How does age impact the PPV of cell free DNA screening for T21?

A

Increases with increasing gestational age, due to an increasing prevalence

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15
Q

When you perform an amniocentesis for genetic testing, what do you order?

A

microarray

other testing as needed

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16
Q

What is a microarray?

A

It is high resolution whole genomic sequencing technique using DNA primers to bind complimentary DNA

Can identify problems detected by conventional karyotype as well as small micro deletions or duplications.

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17
Q

What is the benefit of a microarray on top of a karyotyoe in an anomaly?

A

6% more abnormal genetic findings when we look at microarray

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18
Q

What is the significance of a cell free DNA result that states “low fetal fraction”?

A

Can be an abnormality the test cannot pick up

Can also have a false negative

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19
Q

What is fetal fraction dependent on?

A 
Gestational age
BMI
Medication exposure (lovenox, decreases it)
Maternal conditions
Singletons / Twins
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20
Q

How do you counsel regarding invasive testing / aneuploidy screening?

A

Discuss the risks and benefits of diagnosis
Compare other screening tests
Discuss the detection rate of aneuploiides other than T21
and the type and prognosis of the aneuploidies likely to be missed by serum screening

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21
Q

Describe how you perform an amniocentesis?

A

Skin cleansed with iodine based solution
Ultrasound guidance used continuously
Transabdominal aspiration of fluid (20-30cc)

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22
Q

At what gestational age can you perform an amniocentesis?

A

15-16 or higher (when chorion and amnion fuse)

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23
Q

What are the risks of amniocentesis?

A

Infection
Rupture of membrane
Bleeing
Pregnancy loss (1/1000)

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24
Q

Advantages of CVS?
Disadvantages ?
Timing?

A

Advantages; Earlier information

Disadvantages:
Confined placental mosaicism
Cannot test for NTDs
Maternal cell contamination
Cannot examine methylation (fragile x)

Timing: 10-14 weeks

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25
Q

What are the risks of CVS?

What are the risks of performing a CVS prior to 10 weeks?

A

Bleeding
Rupture of membranes (<1%)
Infection (<1%)
Pregnancy loss (1/200-1/300)

Prior to 10 weeks: limb defects

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26
Q

Contraindications to transcervical CVS?

A

Vaginal infection (Chlamydia /gonorrhea)
Active herpes
Low lying myoma

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27
Q

35 yo G1 with increased NT
CVS shows 46,XX [10], 47,XX +14 [20]
How do you counsel her about this test result?

A

Can be normal with placental mosaicism
Can be abnormal
Or baby could be mosaic

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28
Q

How do you counsel a patient with suspected mosaic trisomy of fetus?

A

Cannot be sure which cells are mosaic (skin, brain, heart, etc…)
So we don’t know the severity
Can be anywhere from as severe as a full trisomy vs. a milder form
No way to be sure

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29
Q

What are the phenotypic features of T21?

A 
Flattened face
Small ears
Short neck
Outside corners of eyes are pointed upward
Narrow high arch palate
Single crease across the palms
Sandal gap feet
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30
Q

What are soft markers for T21 on US?

A 
Thickened nuchal fold
Absent nasal bone
Short limbs
Pyelectasis
Echogenic bowel
Echogenic intracardiac focus
Single umbilical artery
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31
Q

Which soft marker carriest the highest likelhood for T21?

A

Nuchal fold (LR of 11-18)

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32
Q

How do you counsel a patient at 12 weeks with confirmed T21?

A 
Expectant management verses pregnancy termination
Increased risk of pregnancy loss
Increased risk of anomalies
Varying degree of intellectual ability
Increased risk of Leukemia
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33
Q

How do you counsel a patient at 12 weeks with confirmed T21 and hydrops?

A

Prognosis is grave, 90% risk of fetal death.

Offer termination of pregnancy

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34
Q

What is the likelhood of spontaneous abortion for a fetus with T21 and hydrops?

A

Very high

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35
Q

What % of first trimester spontaneous abortions are related to T21?

A

~10%

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36
Q

Differential diagnosis for 1st trimester cystic hygroma?

A 
51% have an abnormal karyotype
#1 Trisomy 21
#2 45X
also possible other trisomies, triploidy, noonan
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37
Q

What % of fetuses with a cystic hygroma in the first trimester will be diagnosed with T21?
Turners?
T18?

A

T21: 33%
Turner: 30%
T18: 20%

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38
Q

Why do we use Multiples of the median?

A

Gives reference values across multiple gestational ages

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39
Q

Quad screen results in: T21

A

Increased: Inhibin A, hCG, decreased: AFP, estriol

*say Hi

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40
Q

Quad screen results in: T18

A

All are low

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41
Q

Quad screen results in: T13

A

All are low

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42
Q

Quad screen results in: Omphalocele, Gastroschisis, twins, NTD

A

Increased AFP

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43
Q

What condition should be suspected with exremely low Estriol (<0.15 MoM)?

A

Smith lemli opitz

X linked iccthyoses (Steroid sulfatase deficiency)

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44
Q

What does aneuploidy screening not find?

A

translocations, inversions, ring chromosomes, single gene mutation

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45
Q

If CfDNA shows mosaic for 46xx and 45xo, what are the possible reasons?

A

(1) Fetus with mosaic monosomy x
(2) Mom with mosaic monosomy x
(3) Confined placental mosaicism

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46
Q

What is the recurrence risk of a fetus with Mosaic 45Xo?

A

Test the mom and dad for mosaicism

If negative, discuss the risk of gonadal mosaicism

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47
Q

What is the best aneuploidy screening test for a patient with leg cancer?

A

Amniocentesis
if not, can do quad screen
With active cancer, can have aneuploid cell turnover

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48
Q

Approach to a patient with Multiple aneuploidies on cfDNA with no known cancer?

A

Blood smear, physical exam, imaging looking for cancer

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49
Q

Can you do cell free DNA in twins?

A

Yes, but there are limitations
Positive results but cant be sure which baby is affected
No method of aneuploidy screening that includes a serum sample is as accurate in twin gestations as it is in singleton pregnancies

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50
Q

If fetal T21 is suspected, how do you counsel the patient regarding additional testing options?

A

CVS vs. amniocentesis depending on gestational age

Postnatal testing

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51
Q

Who should be offered cell free DNA screening?

A

All patients

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52
Q

Limitations of cell free DNA screening?

A 
Low fetal fraction
Confined placental mosaicism
Co-twin demise (vanishing twin, false results)
Tumors
Sex discordance
maternal deletion/duplication
maternal mosaicism
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53
Q

How accurate is cell free DNA screening in the detection of fetal T21?

A

It is the most accurate screen for trisomy 21

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54
Q

What can cause False positive results for cfDNA?

A

Maternal malignancy
Maternal karyotype abnormality
Placental mosaicism
Demise of co-twin

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55
Q

What does a failed cfDNA mean?

A

Increased risk for aneuploidy or another genetic abnormality

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56
Q

What are possible explanations for cell free DNA results indicating high risk for T21?

A 
Mosaic placenta
Aneuploid placenta
Aneuploid fetus
Mosaic mom
False positive
Resorbed twin
Maternal malignancy
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57
Q

How do you counsel a 39 yo patient with a positive cell free DNA result for T21?

A

High likelihood its a true positive >90%

Can confirm with invasive testing

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58
Q

How do you counsel a 29 yo patient with a positive cell free DNA result for T21?

A

Medium likelhood its a true positive 50-60%

Can confirm with invasive testing

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59
Q

What are the most common anomalies in a fetus with T21?

A

AVSD

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60
Q

What causes a double bubble sign on US?

A

Duodenal atresia

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61
Q

Can a microarray detect T21?

A

Yes, by detecting copy number variants

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62
Q

What is cytogenetic analysis?

A

Need live rapidly growing cells (WBCs or amniocytes)
Culture
Stimulate cells to divide
Arrest in metaphase
Treat with solution to break open cells
Chromosomes fixed, spread on slides and stained

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63
Q

What is FISH?

A

Fluorescence in situ hybridization

Chromosome specific probes

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64
Q

Benefits of FISH?

Disadvantages?

A

Quick (24-48 hours)
Can be performed on non-dividing interphase

Disadvantages:
Can have false negatives
Not diagnostic

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65
Q

What are the benefits/ disadvantages of a Karyotype?

A

Chromosomal rearrangements
Large deletions / duplications
Balanced structural rearrangements

Disadvantages:
Miss microdeletions / microduplications
Need live cells that are able to grow

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66
Q

What advantages does a fetal karyotype have over microarray in a fetus with T21

A

Microarray cant tell you if you have 3 separate copies or 2 copies attached to each other, and this is important for recurrence counseling

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67
Q

Most common mechanism for T21?

A

Meiotic nondisjunction in meiosis I

68
Q

What are the types of translocations?

A

Reciprocal/Balanced: two pieces switch

Robertsonian: rearrangement with two acrocentric chromosomes (so get one chromosome with 2 q arms)

69
Q

How do you interpret this cvs result?
46, XX[20], 47, XX+7[10]?

Next steps?

A

Mosaicism with additional chromosome 7
Could be fetal mosaicism
Confined placental mosaicism
Could be maternal mosaicism

Next step: Test amniocytes
Rules out confined placental mosaicism

70
Q

What is the risk of recurrence?

46, XX[20], 47, XX+7[10]?

A

Low….

? 24:10 left d02v05

71
Q

What does a chromosomal microarray allow you to see?

A

Microdeletions / duplications

72
Q

Karyotype vs Microarray, pros /cons

A

Karyiotype detects: large del/dup, balanced translocations, triploidy
Karyotype cannot detect: small dels/dups
Microarray detects: microdels/microdups, unbalanced translocation, triploidy (snp based), areas of homozygosity
Microarray cannot detect: Balanced translocations

73
Q

What test should you offer for a major structural anomaly?

A

CMA (replaces the need for fetal karyotype)

6-7% more detection than a normal karyotype

74
Q

What test should you send for a structurally normal fetus?

A

Either karyotype or CMA

75
Q

What test should you send for an IUFD?

A

CMA

76
Q

You are seeing a consultation of history of fetal demise at 30 weeks. She chose limited autopsy with no specific finding and now you have microarray results:
VUS in WNT gene
What are your next steps in analysis and how do you counsel the couple?

A 
Parental testing (targeted microarray)
Cannot be sure if this is the reason the baby died. 
Counsel that VUS can be associated with adverse outcomes, but there is no clear information about this variants at this time.
If none of them has this abnormality, it is unlikely to recur because it was a de novo mutation
If one of them does have it, but has a normal phenotype, then there is a higher chance its a non pathogenic variant (but cant be sure)
77
Q

How do you follow a patient during pregnancy with T21?

A

Detailed anatomic survey
Fetal echocardiogram
Fetal growth
Antenatal testing at 32 weeks

78
Q

How do you counsel a patient regarding recurrence risks for T21?

A

Non-inherited extra chromosome -> 1% recurrence (or age dependent)
Translocated Down syndrome -> 50% recurrence

79
Q

What ultrasound findings would lead you to suspect T18?

A 
MORE
Micrognathia
Omphalocele
Rocker bottom feet
Ears low set
Cephalic -Brachycephaly (strawberry head)
Celes (omphalocele/ meningomyocele)
Clenched hands overlapping digits
Choroid plexus cyst
Cleft lip/palate 
CDH
Cardiac defect 
Posterior fossa abnormalities
Nuchal translucency verses cystic hygroma
80
Q

If fetal T18 is suspected, how do you counsel the patient regarding additional testing options?

A

Recommend diagnostic testing with amniocentesis or CVS

NIPT if patient declines diagnostic testing

81
Q

How accurate is cell free DNA screening in the detection of fetal T18?

A

High false positives (depending on maternal age)

Low false negatives

82
Q

What are possible explanations for cell free DNA results indicating high risk for T18?

A 
Mosaic placenta
Aneuploid placenta
Aneuploid fetus
Mosaic mom
False positive
Resorbed twin
Maternal malignancy
83
Q

How do you counsel a 39 yo patient with a positive cell free DNA result for T18?

A

60% chance its a true positive

84
Q

How do you counsel a 29 yo patient with a positive cell free DNA result for T18?

A

20% chance its a true positive

85
Q

How do you counsel a patient about prognosis with confirmed T18?

A 
Poor prognosis (
50% IUFD, 
20% survive beyond 1st month
5-10% survive beyond 1st year
Can consider termination of pregnancy
86
Q

If the patient continues the pregnancy with a T18 fetus, what complications may develop?

A

FGR
Polyhydramnios
Fetal death

87
Q

If the fetus w/ T18 is born alive, what is the likelihood of survival?

A

10% to age >1

88
Q

Do you offer c/s for fetuses with T18?

A

Discuss a shared decision making model, explain to patient that cesarean section puts her at risk and that a t18 fetus has a low probability of survival.

89
Q

Will you perform intrapartum fetal monitoring for fetuses with T18?

A

Shared decision making, explain to them that we may find heart rate abnormalities that cause us to intervene and that they may not improve the ability of the fetus to survive.

90
Q

What US findings would lead you to suspect Turner Syndrome?

A 
Cystic hygroma
Coarctation of aorta in female fetus
Pelvic Kidneys
Fetal edema
Horseshow kidney
Non-immune hydrops
91
Q

How does Turner Syndrome occur?

A

Instability of the Y chromosome in the sperm. 80% occur when an egg fertilized with sperm lacking a X chromosome

92
Q

Is Turner Syndrome associated with maternal age?

A

No

93
Q

What are the phenotypic features of Turner Syndrome?

A 
Short stature
Webbed neck
Coarctation of the aorta
Hypoplasia left heart 
Renal defect
Gonadal dysgenesis
94
Q

How do you counsel a patient at 12 weeks with confirmed fetal Turner Syndrome?

A

Increased risk of miscarriage
There is an increased risk of cardiac and other anomalies
High risk of fetal loss prior to delivery

95
Q

How do you counsel a patient at 12 weeks with confirmed fetal Turner Syndrome and hydrops?

A

Very high risk of pregnancy loss / fetal death

96
Q

What % of first trimester spontaneous abortions are related to Turner Syndrome?

A

10%

97
Q

What percentage of fetuses with a cystic hygroma in the first trimester will be diagnosed with Turner Syndrome?

A

30%

98
Q

How accurate is cell free DNA screening in the detection of Turner Syndrome?

A

Very good NPV

40/60 PPV

99
Q

What are possible explanations for cell free fetal DNA results indicating high risk for Turner Syndrome?

A 
Mosaic placenta
Aneuploid placenta
Aneuploid fetus
Mosaic mom
False positive
Resorbed twin
Maternal malignancy
100
Q

How do you follow a patient during pregnancy with fetal Turner Syndrome?

A

Detailed anatomy
Fetal echo
Serial growth u/s
Weekly testing near term

101
Q

How do you counsel a patient regarding recurrence risks for Turner Syndrome?

A

Low risk because it is sporadic

102
Q

How is Noonan Syndrome inherited?

A

Autosomal Dominant (PTPN 11 gene mutation) - Usually De Novo

103
Q

What is the classic phenotype of Noonan syndrome?

A 
Short stature
Webbed neck / lymphedema
Pulmonary stenosis (sometimes Pulm HTN)
Cardiomyopathy
Micrognathia
Wide spaced eyes
Delayed puberty
Pectus carinatum or excavation
Developmental delay
Spine
104
Q

What US findings are suspicious of Noonan syndrome?

A

Thickened NT >4.0

105
Q

What is the most common cardiac defect with Noonan syndrome?

A

Pulmonary stenosis

Idiopathic cardiomyopathy

106
Q

What is the prognosis for a fetus diagnosed with Noonan syndrome?

A

Related to presence or absence of cardiac abnormalities.

Can have issues as baby but usually improve and lead mostly normal lives

failure to thrive
Learning disability/ Mild intellectual impairment
Delayed puberty

107
Q

What diseases should ashkenazi jews be screened for?

A

CF
Tay sachs
Familia dysautonomia
Canavan disease

108
Q

What is Fragile X syndrome?

A

CGG trinucleotide repeat, that expands and can lead to intellectual disability when it reaches full mutation.

109
Q

What patients should be screened for their Fragile X syndrome carrier status?

A

Relatives with intellectual disability
Early menopause
Personal/family history of intention tremor and cerebellar ataxia

110
Q

What are the phenotypic features of Fragile X syndrome?

A 
Mental retardation (most common inherited intellectual disability)
Prominent jaw
Long face
Large ears
Macroorchidism
111
Q

What phenotype do women express who are pre-mutation carriers for Fragile X syndrome?

A

They can have premature ovarian failure

and/or ataxia syndrome

112
Q

What is the inheritance of Fragile X syndrome?

A

X-linked dominant

113
Q

Can a female with a full mutation have Fragile X syndrome?

A

Yes, but it is usually milder thru skewed X inactivation

114
Q

What is a premutation carrier for Fragile X syndrome?

A

55-200, increaased risk of expansion to a full mutation

Can have some associated issues (Premature ovarian failure, tremor/ataxia syndrome)

115
Q

How do AGG triplets affect Fragile X?

A

Intervening AGG makes it more stable, and reduces the risk of expansion

116
Q

What does it mean to say someone carries the full mutation for Fragile X syndrome?

A

The expansion from anticipation of the repeat has reached a critical level where the features of the disease begin to show

117
Q

What gene is affected with Fragile X syndrome?

A

FMR1 gene

118
Q

How does methylation of the FMR1 gene lead to Fragile X syndrome?

A

FMR1 protein is important for neurons, with expansion of the CGG, there is methylation which causes less producton of this protein

119
Q

What are other examples of trinucleotide expansion repeat disorders?

A

myotonic dystrophy

huntingtons

120
Q

Is Fragile X syndrome inherited through the mother or the father?

A

Both, but increased risk when comes from the mom

121
Q

Explain the concept of anticipation?

A

Increasing repeats with every generation, at a certain level (>200 in fragile x) its enough to cause instability and can stop transcription resulting in disease

122
Q

How do you test a fetus to see if has full mutation?

A

CVS or Amnio (PCR or Southern blot)

123
Q

Why is amnio preferred for Fragile X testing?

A

If there are indeterminate results, and methylation needs to be done
Methylation testing can only be done with amnio because CVS is placental

124
Q

What is myotonic dystrophy?

A

AD inherited trinucleotide repeat disorder which can cause cataract, hypotonia, muscle weakness.

125
Q

What ultrasound features can be identified in a fetus with myotonic dystrophy?

A

Polyhydramnios

126
Q

How is myotonic dystrophy inherited?

A

Autosomal dominant inheritance (CTG trinucleotide repeats)

127
Q

Classic physical exam finding in myotonic dystrophy?

A

Difficulty letting go/releasing grip

128
Q

What is the phenotype of myotonic dystrophy?

A

> 50 CTG: Mild: cataract , myotonia ,late onset
Moderate: muscle weakness, cataracts, onset at 20-30yrs
1000 CTG: severe: congenital, polyhydramnios, developmental delays, hypotonia

129
Q

What patients should be screened for myotonic dystrophy carrier status?

A

Family history of weakness / cataracts

130
Q

Is myotonic dystrophy associated with maternal or paternal expansion of trinucleotide repeats?

A

Maternal

131
Q

What is a pre-mutation carrier for myotonic dystrophy?

A

38-49

132
Q

Phenotype of huntingtons?

A

Progressive neurodegnative condition
Chorea movements
Dementia

133
Q

What is the full mutation cutoff for huntingtons?

A

40

134
Q

In huntingtons, is expansion risk greater with paternal or maternal inheritance?

A

Paternal

135
Q

What is exclusion testing?

A

If a grandparent has a disease like huntingtons, can test to see whether child is inheriting that gene area from the affected grandparent (without specifying whether its the affected one or unaffected one) or the unaffected grandparent.
This allows excluding disease without testing / telling the parent about their status.

136
Q

What is the phenotype for Prader-Willi Syndrome?

A 
Hypotonia
Poor cry
Lethargy
Small penis
Small hands/feet
Childhood hyperphagia (obesity)
Cognitive impairment
137
Q

Which chromosome is involved in Prader-Willi Syndrome?

A

Chromosome 15 - loss of dads (prader no father)

138
Q

What is the prognosis for Prader-Willi Syndrome?

A

not life-threatening, but compulsive eating and weight gain can cause young adults with the syndrome to develop serious obesity-related conditions such as: type 2 diabetes.

139
Q

What is an imprinting disorder?

A

Epigenetic phenomenon that causes genes to be expressed or not depending on whether they are inherited from the mother or the father

140
Q

What are 3 explanations for how Prader-Willi Syndrome occur?

A

(1) Paternal deletion chrom 15
(2) Maternal UPD chrom 15
(3) Imprinting defect on chrom 15

141
Q

What is uniparental disomy? Increases risk of?

A

Getting 2 copies of a chromosome from one parent (6,7,11,14,15)
At first you get two from one parent 1 from the other and trisomic rescue occurs to kick out one of them, leading to a cell with 2 of a certain chromosome from one parent.
Increased risk of imprinting disorders

142
Q

If Prader-Willi Syndrome develops as a result of UPD, are there two copies of the maternal or paternal chromosome?

A

Maternal

143
Q

How is prader-willi syndrome tested for?

A

Parent specific - DNA methylation analysis on PW region of chrom 15

144
Q

What US findings may be associated with Prader-Willi Syndrome?

A

None really

145
Q

What is the phenotype for Angelman syndrome?

A

Happy puppet
Dev delay
Seizures
Ataxia

146
Q

Which chromosome is involved in Angelman syndrome?

A

Chrom 15

147
Q

What are the 3 explanations for how Angelman syndrome occurs?

A

(1) Deletion of maternal
(2) Paternal uniparental disomy
(3) Imprinting defect on Chrom 15

148
Q

If Angelman syndrome develops as a result of UPD, are there two copies of the maternal or paternal chromosome?

A

Paternal

149
Q

What is the prognosis for Angelman syndrome?

A

Severe developmental delay
Speech limitations
Motor dificulties
Normal life spans

150
Q

What is the classic phenotype of Di George Syndrome?

A

Congenital heart defects (conotruncal most specific, Tetralogy most common)
Abnormal facies
Thymic hypoplasia (Decreased T cell immunity)
Cleft palate
Hypoparathyroid

151
Q

What US abnormalities would make you suspect a 22q11 deletion?

A

Congenital heart defects (conotruncal most specific, Tetralogy most common)
Cleft palate

152
Q

How is a 22q11 deletion syndrome inherited?

A

Autosomal Dominant (usually de novo)

153
Q

If you perform an amniocentesis, what studies will you send on the amniotic fluid to test for 22q11 deletion syndrome?

A

Direct FISH CMA

154
Q

What are the pitfalls of using cell free DNA screening in cases of suspected fetal 22q11 deletion syndrome?

A

Most of these microdeletions are extremely rare. Given the very low prevalence of these conditions, most positive test results will be false positives, and the positive predictive value of the test is very low.

155
Q

What percentage of fetuses with 22q11 Deletion syndrome will have a cardiac defect on US?

A

75%

156
Q

What is the most common cardiac defect in 22q11 deletion syndrome?

A

Tetralogy

157
Q

What non-cardiac issues can be found in individuals with 22q11 deletion syndrome?

A

Learning disabilities
Immune issues (thymic hypoplasia)
Cleft palate

158
Q

What are the classic US findings in Beckwith Wiedemann Syndrome?

A

Polyhydramnios
Large for gestational age
Omphalocele
Macroglossia

159
Q

What are the genetics of Beckwith Wiedemann Syndrome?

A

Epigenetic changes (methylation) in embryos in media, imprinted regions of 11

160
Q

What is the prognosis for a fetus with Beckwith Wiedemann Syndrome?

A

Good prognosis, normal lfe expectancy

They grow up to be healthy adults

161
Q

If you suspect a fetus of having Beckwith Wiedemann Syndrome, what testing will you perform on the amniotic fluid?

A

DNA Methylation testing

162
Q

What clinical findings are there in patients with CF?

A

Respiratory: Bronchiectasis
Pancreas: Pancreatic insufficiency
Sweat glands: Increased Na in sweat (dehydration)
Infertility

163
Q

What testing do we do to assess risk for CF?

A

CFTR mutation panel

164
Q

Limitations of CFTR mutation panel?

A

Tests the most common mutations

In negative results, it doesnt rule out a mutation, just rules out the mutations tested

165
Q

Clinical findings in patients with Spinal muscular atrophy (SMA)?

A

Hypotonia
Absent DTRs
Respiratory compromise
#1 genetic killer of children <2

166
Q

Can you be a carrier for SMA if you have 2 copies of SMN1?

A

Yes, if they are in cis configuration

2022 - MFM ORAL BOARDS ALL (6 decks)

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