Dysmorphology, etc

Question 1

cleft lip/palate - what percent will have syndrome?

Answer 1

about one third.

Question 2

primary anomaly example

Answer 2

clefts

Question 3

deformation

• • primary or secondary?
• • examples?

Answer 3

SECONDARY
Compression or biomechanical distortion of an already normally formed body part which usually occurs after 8 – 10 fetal weeks

plagiocephaly
club feet
contractures
dislocations

Question 4

disruption

• • primary or secondary?
• • examples?

Answer 4

SECONDARY
Compression / biomechanical distortion of an already formed (or to be formed) normal body part to such an extreme that the resulting defect looks like an anomaly

Ex: oligodactyly due to amniotic bands, cleft palate due to glossoptosis; web neck due to nuchal edema

Question 5

Blastogenic defects

– examples?

Answer 5

very early defect in embryogenesis during which time the embryo is acquiring craniocaudal, dorsoventral, and left-right axes

affects midline formation and lateralization

Associated with increased abortions, twinning and lethality
Genetic basis rare, low recurrence risk

conjoined twins, acardia-acephalus, situs inversus/poly-asplenia, bladder extrophy, sacral defects / tumors

Question 6

major anomaly

Answer 6

Basic alteration in embryological development severe enough to require intervention and which potentially has a long-term impact medically and/or psychologically

Ex: spina bifida, omphalocele (40% syndromic), bilateral cleft lip/palate, anopthalmia

Question 7

minor anomaly

Answer 7

Basic alteration in embrylogical and/or fetal development which requires no treatment or can be, more or less, corrected

Ex: postaxial polydactyly, absent digital flexion creases, low-set ears, preauricular tag

Question 8

multiple congenital anomalies

Answer 8

• two or more
  structural primary defects in two or more areas,
  or embryologically diff. areas.
• usually associated with recognizable syndrome

Examples: ectrodactyly-ectodermal-clefting
(EEC) syndrome;
oral-facial-digital (OFD) syndrome

Question 9

syndrome

Answer 9

Recurring pattern of structural defects and/or secondary effects/defects that allow for secure recognition

Combination of features most likely represents a specific etiology

Example: SC-Pseudothalidomide / Roberts syndrome

Question 10

Potter syndrome

- recurrence risk

Answer 10

• recurrence risk low
• oligohydramnios -> pulmonary hypoplasia -> joint contractures -> abn ear cartilage -> lower inner eye folds -> prominent nasal tip

can also be part of a syndrome.

Question 11

Pierre Robin sequence

- recurrence risk

Answer 11

• recurrence risk is low
• micrognathia -> glossoptosis -> CLEFT PALATE -> low-set ears

glossoptosis = downward movement/displacement of tongue, can cause cleft palate.

PR can also be part of syndrome.

Question 12

Amniotic band sequence

- recurrence risk

Answer 12

• recurrence risk is low

- bands –> constrictions –> fusions –> amputations –>CLEFT LIP/PALATE –> OMPHALOCELE

Question 13

spondylo-

Answer 13

affecting the spine

e.g., spondyloepiphyseal dysplasia (bone issue)

Question 14

rhizomelic -

Answer 14

affecting PROXIMAL bone

(rhizome = root ) ; root of arm

Question 15

bone dysplasias - recurrence risk?

Answer 15

Almost always associated with disproportionate short stature and is usually genetic

Question 16

bone dysostosis -

Answer 16

Localized defect of bone which does
not necessarily involve the physes

Often unilateral but can be midline

Examples: Klippel-Feil (fused cervical vertebrae), ulna-mammary syndrome, proximal femoral hypoplasia

Question 17

disorganization

Answer 17

A situation where there is the presence of an extraordinary variety of unusual anomalies which defy embryologic patterns:
Ex: limbs/digits attached to non-joint areas, skin appendages in unusual locations, duplication of limbs/digits

–unknown etiology.

Question 18

Noonan - gene?

Answer 18

PTPN 11 (controls SHP-2)

pulmonary stenosis
but not much HCM

Question 19

Zellweger

Answer 19

recessive

Usually associated with increased VLCFA

severe hypotonia / early death
large anterior fontanel, increased lateral and anterior NECK FAT (double chin), narrow palpebral fissures, prominent upslanted eyes, cataracts, club feet, stippled epiphyses

1 in 20k - 100k

Question 20

Russel-Silver

Answer 20

many jockeys have it (horse jockeys are tiny)

UPD 7 ; paternally imprinted

10% maternal uniparental disomy for chromosome 7; some have hpomethylation of H19 gene at 11p15

Proportionate pre-/postnatal growth def. (wt and ht) with usually low-normal head circ.

Features: triangular face, thin upper lip with down turned mouth corners, incurved/short 5th fingers, asymmetry (50%) of limb size, infancy excessive sweating

I.Q. normal. Slight increased risk of urogenital anomalies

Question 21

Anhidrotic (absent), hypohidrotic (reduced) sweating

Hypotrichosis of scalp/eyebrows/eyelashes (sparse)

Conical teeth, oligodontia

Other features: mildly flat nasal bridge, rosy red lips, periorbital hyperpigmentation, markedly reduced sweat pores

Answer 21

X-linked hypohidrotic ectodermal dysplasia

Incidence: 1 in 20,000 (most common ED)

Etiology: mutation in EDA1 gene at Xq12-q13.1

The Ectodermal Dysplasias (EDs) are genetic disorders affecting the development or function of the teeth, hair, nails and sweat glands (>150 EDs are known).

Question 22

Obesity, 
polydactyly   [almost universal]
retinitis pigmentosa 
         [tunnel vision/poor night vision, later childhood]
Hypogenitalism (males), 
renal degeneration, 
mental retardation

brain, fat, eye, genitals, kidney

Answer 22

Bardet-Biedl syndrome (BBS, AR)
pronounced barDAY-beedl

some cases: TRI-ALLELIC inheritance – like recessive, but need three mutations in BBS2/BBS6

common in middle east
1 in 13,500 (Middle East)
1 in 125,000 (England)

vs: Prader Willi - also has some MR, hypogenitalism, but NO polydactyly/retinitis pigmentosa, kidney stuff.
Prader willi: short stature, small hands, stubbornness, narrow forhead, almond-shaped eyes, triangular mouth, skin picking, hyperphagia (^^ appetite)

Question 23

Features: LONG PALPEBRAL FISSUES, arched eyebrows, lower EYELID EVERSION, flat nasal bridge, short nasal septum, prominent abnormal ears, large fingertip pads, short 5th fingers, MR, microcephaly, mixed growth problems

Lower frequency features: FTT, reflux, heart defects, long eyelashes, hypoglycemia, hypotonia, lagophthalmos (can’t close eyes), immune problems, late obesity

Answer 23

similar to 22 q…. but it’s Kabuki

unknown inheritance, usually sporadic

Incidence: 1 in 32,000/86,000 (?AR)

Etiology: Unknown; report of 8p22-8p23.1 duplication not found to be significant in follow-up reports

Few familial cases (?AD inheritance)

Question 24

premature aging after early normal infancy, growth deficiency in childhood,
loss of subcutaneous fat, thinning of skin,
acquired thin beaked nose,
prominent subcutaneous vessels,
worsening hypotrichosis,
early death (2nd decade) due to coronary artery disease, arteriosclerosis, and strokes

Answer 24

Progeria, 1 in 8 million

mutation in Lamin A/C gene at 1q21-1q23 region; mutations in same gene can cause mandibuloacral dysplasia, CMT 2B, AR Emery-Dreifuss MD, and others representing a “family” of disorders

Question 25

Increased spontaneous chromosome breakage, which is increased by DNA cross linking agents Significant increased risk of neoplasia, e.g., leukemia THUMB/radial hypoplasia, hyperpigmentation, short stature, pancytopenia (onset after 3 years - loss of all three types of blood cells - red/white/platelets) BONE MARROW FAILURE

Answer 25

Fanconi Anemia (AR) 1 in 26-400 k FancA-H genes; FancA = 65% of cases

Question 26

Rett syndrome - inheritance?

Answer 26

XL-dominant, typically male lethal 1 in 15,000 MR, spasticity, hand-wringing, inconsolable crying, NO facial dysmophism

Question 27

scarcity of bile ducts (cholestasis), heart defects (PS/PPS), vertebral anomalies with characteristic facial features (deep-set eyes, posterior embryotoxin (eye), high triangular shaped nasal bridge, full nasal tip) Mild MR may occur

Answer 27

ALAGILLE SYNDROME (AD) 1 in 70,000 differential dx for 22q

Question 28

Eyes: retinal lacunae (punched-out retinal lesions with choroid showing through) ``` seizures --> should prompt eye exam severe MR agenesis corpus collosum little/no speech vertebral defects polydactyly perinatal anoxia face - no dysmorphic features ```

Answer 28

Aicardi syndrome (XL dominant) rare

Question 29

macrocephaly, frontal bossing, hypertelorism, polydactyly (broad thumbs/hallices), syndactyly agenesis corpus callosum

Answer 29

Greig Cephalopolysyndactyly (AD) GLI3 Mutation in GLI3 also in Pallister-Hall syndrome (hypothalamic hamartomas and postaxial polydactyly)

Question 30

mixed polydactyly and tongue hamartomas MR, clefting, hypertelorism, agenesis corpus callosum, Dandy-Walker cyst

Answer 30

Oral-Facial-Digital syndromes (OFD) (XL,AR,?AD) At least 9 OFD syndromes identified

Question 31

ectrodactyly (split hand/foot malformation) cleft lip/palate obstructed lacrimal ducts sparse hair

Answer 31

Ectrodactyly-Ectodermal-Clefting EEC, Type 3 (AD) mutation in P63 gene at 3q27 Type 1 on 7q ; Type 2 on chr20 Mutations in P63 gene also associated with Hay-Wells,Rapp-Hodgkin, limb mammary syndrome, Adult syn, and ectrodactyly (split hand/foot, type 4) Despite P63 mutations, no increase in neoplasia Greek ektroma (abortion) and daktylos (finger) = literally, abortion (of a) finger,[2] involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation

Question 32

“tree frog” digits with short and broad thumbs/hallices

Answer 32

Oto-Palato-Digital syndrome (I/II) AD Cleft palate, hypertelorism, conductive deafness, mild mental retardation, “tree frog” digits with short and broad thumbs/hallices, bowed limbs (mostly lower extrem.) Type II tibiae/fibulae much shorter and fibulae can be absent. Also risk of omphalocele. Mutations of filamin A also cause Melnick-Needles, frontometaphyseal dysplasia, and, surprisingly, XL periventricular nodular heterotopia

Question 33

High risk of BASAL CELL CARCINOMA increased risk of medulloblastoma and ovarian tumors macrocephaly, high prominent forehead, hypertelorism, flat nasal bridge, jaw cysts, calcified falx (white at bottom of cranium) Other: PALM PITS (otherwise rare), polydactyly, pectus, bifid ribs, cleft lip / palate

Answer 33

Basal Cell Nevus (Gorlin syndrome) AD PTCH gene, 1 in 60,000

Question 34

``` postaxial polydactyly (ulnar/pinky side) clenched fists ```

Answer 34

Trisomy 13

Question 35

clenched fist with 2nd and 4th fingers on top of middle finger

Answer 35

Trisomy 18

Question 36

small baby premature lots of arches on dermatoglyphics (fingerprints)

Answer 36

Trisomy 18 arches are not fully-developed

Question 37

mesomelic ***

Answer 37

shortening of long bones (the one farther from the body - distal)

Question 38

``` frontal bossing with high, receeding hairline supernumerary nipples umbilical hernia patches of hypo- or hyper- pigmentation MR seizures ```

Answer 38

Pallister-Killian mosaicism for tetrasomy of 12p.

Question 39

PTPN11 - gain of function syndrome? - loss of function syndrome?

Answer 39

PTPN11 - gain of function syndrome -- Noonan - loss of function syndrome -- Leopard (multiple lentigines syndrome, HCM)

Question 40

1 in _ kids has a developmental disability

Answer 40

1 in 6 = 15% autism, palsies (motor), ADHD, MR, neurodevelopmental

Question 41

intellectual disability prevalence

Answer 41

1 in 91

Question 42

Autism spectrum prevalence

Answer 42

1 in 68

Question 43

"developmental delay"

Answer 43

only used until age 5

Question 44

developmental delay, ID, or ASD of unknown cause : first tier recommendations?

Answer 44

Fragile X microarray ...WG sequencing being used more and more as 2nd

Question 45

Developmental disabilities - what percent is due to CNV? single gene? unknown cause?

Answer 45

CNV? ~20% single gene? ~35% unknown cause? ~45% genetic etiology can be identified in up to 40% !! if include whole exome sequencing + microarray

Question 46

16p11.2 del

Answer 46

one of most common causes of | Autism, DD/ID, Macrocephaly

Question 47

concept: microdel/dups that are associated with developmental disabilities are now being found in adults, and are associated with ___

Answer 47

psychiatric disorders and epilepsy e.g., 22q, 16p11.2 del, 1q21.1 del, 15q11.2 (prader-willi/angelman)

Question 48

Fragile X

Answer 48

1 in 3600 - males 1 in 6000 - females .....1 in 36 males with intellectual disability of unknown cause has Fragile X!!! Most common known inherited cause of ID, ASD

Question 49

Females with FMR1 Full Mutations

Answer 49

MINORITY without developmental symptoms Often (not always) less severe intellectual impairment than in males Mild to moderate ID, ASD, learning disabilities, psychiatric disorders Long face, prominent ears (more subtle than in males) Poor eye contact, attentional problems, shyness and social anxiety

Question 50

~ 1 in ___ children with ASD has FXS as the underlying cause

Answer 50

~ 1 in 20 children with ASD has FXS as the underlying cause Fragile X: most common known single gene cause of autism

Question 51

FMR1 Premutations prevalence FMR1 expands in

Answer 51

Premutation prevalence: 1 in 151 females 1 in 468 males FMR1 expands in mothers to full mutations in sons and daughters Paternal premutations pass to daughters, usually with minimal expansion and can have small contractions

Question 52

FMR1 expansions are moderated by

Answer 52

AGG interruptions = stabilizing effect on CGG repeats

Question 53

Fragile X-associated Tremor Ataxia Syndrome (FXTAS)

Answer 53

Progressive ataxia, tremors, personality changes ~40-50% of premutation males >age 50 have symptoms ~8–17% of premutation females develop FXTAS symptoms in late adulthood, often less severe Males, females with full mutations not at risk for FXPOI / FXTAS BUT Individuals with fragile X syndrome and full / premutation mosaicism may be at risk for FXPOI / FXTAS

Question 54

indications for Fragile X syndrome expansions

Answer 54

Diagnostic testing of males and females with ID/DD/ASD of unknown cause Carrier testing for individuals with family history of fragile X or ID/DD/ASD of unknown cause Prenatal diagnosis when mother has known FMR1 mutation Diagnostic testing for women with symptoms of FXPOI, unexplained infertility, early menopause Diagnostic testing for males, females with adult onset ataxia, tremors of unknown cause

Question 55

prenatal: If the median value is 1.5 mm Individual value is 3.0 mm what is MoM?

Answer 55

The MoM = 3.0/1.5 = 2.0

Question 56

prenatal: which markers are measured in 1st trimester?

Answer 56

``` hCG human chorionic gonadotrophin PAPP-A pregnancy associated plasma protein A Inhibin A dimeric inhibin A ``` HIP - (hcg, inhibin a, papp-a) - you're still "hip" in the first trimester because you can move. + nuchal translucency 10-14 weeks

Question 57

prenatal: which markers are measured in 2nd trimester?

Answer 57

``` msAFP alpha fetoprotein Only marker that detects ONTD hCG human chorionic gonadotrophin Inhibin A dimeric inhibin A uE3 unconjugated estriol ``` "a, hui!" Russian expletive/expression like, oh, damn. you can't move in the second trimester - a, hui!

Question 58

1st tri testing timeframe

Answer 58

10-14 weeks

Question 59

Two-part testing (1st and 2nd trimester) Sequential Integrated Contingent

Answer 59

Two-part testing (1st and 2nd trimester) Sequential -- all tests, reported twice; once in 1st, once in 2nd Integrated -- same thing, but results reported once in 2nd Contingent -- second tri testing depends on results of 1st. 1st tri --> CVS/amnio OR 2nd tri OR no 2nd tri test

Question 60

prenatal marker pattern in Down Syndrome

Answer 60

HI is high, rest is low...risk increases w increasing values ``` hcG - high inhibin A - high AFP - low uE3 -low PAPP-A - low ``` vs "normal" = opposite. HI are low, and AU are high.

Question 61

prenatal marker pattern of Tri 18

Answer 61

all 5 markers are low.

Question 62

nuchal - pattern for: DS? other trisomies?

Answer 62

nuchal measurement is high for DS other trisomies

Question 63

cystic hygroma

Answer 63

very big nuchal | high risk of aneuploidy --> go straight to diagnostic test

Question 64

the higher the detection rate, the __er the false positive rate

Answer 64

the higher the detection rate, the HIGHER the false positive rate ...

Question 65

sequential screening in 1st AND 2nd tri has what detection rate for DS?

Answer 65

94%, with 11% false positive rate.

Question 66

ACOG algorithm on hemoglobinopathy testing

Answer 66

CBC + indices if AA --> straight to hemoglobin electrophoresis (1 in 10 is SSD carrier) if SE asian/mediterranean (1in40) --> if anemia (reduced MCV and not low iron), then go to hg electrophoresis. if (+) for Hemoglobinopathy in SE asian, then check for alpha-thalassemia (1 in 20). do NOT do hemoglobin solubility testing.

Question 67

Ashkenazi carrier screening guidelines per ACOG ACMG

Answer 67

``` ACOG: CF Canavan Familial Dysautonomia Tay-sachs (1 in 27) ``` ``` ACMG = ACOG + 5 Gaucher (1 in 15) --> most common recessive AJ disease Mucolipidosis IV (MLIV) Niemann Pick (A) Bloom Fanconi (C) ```

Question 68

Tay Sachs - mechanism? - three forms?

Answer 68

beta-hexosaminidase A (housekeeping gene) gangliosides build up severe neuro degeneration INFANTILE (null) symptoms by 6 months --> regression seizure, blind, deaf, JUVENILE (one null, one low) 2-10 yrs ADULT (one null, and G269S mutation -- some) adolescence-adulthood schizophrenia, neuro variable presentation

Question 69

Tay Sachs - two ways to test - benefits/limitations of both

Answer 69

Hex A enzyme testing in WBC - 97-99% detection - won't tell u which mutation Molecular for mutations - 92-94% detection rate in AJ, lower in non (60%ish) - can identify adult-onset e. g., G269S + null = schizophrenia, neuro in adults

Question 70

SMA detection is worse in African Americans - why?

Answer 70

there's a higher prevalence of having both SMN1 non-mutated copies on one chromosome, and 0 on the other, thereby being a carrier, even if screened negative. Risk *after* initial screening is 1:130, compared to 1:830 in Europeans AA's - SMA - 1 in 70 is a carrier Caucasian - SMA - 1 in 47

Question 71

date of conception relative to last menstrual period?

Answer 71

LMP = self-evident | date of conception = LMP + 2 weeks

Question 72

Warfarin embryopathy

Answer 72

``` Warfarin embryopathy Nasal hypoplasia Stippled epiphyses Limb hypoplasia Critical period 6-9 weeks from conception; 8-11 weeks post-LMP ```

Question 73

Ace-inhibitors for hypertension - when problematic?

Answer 73

structural malformations if taken during 2nd or 3rd trimesters renal tubular dysplasia --> oligohydramnios --> Potter sequence + pulmonary hypoplasia

Question 74

SSRI - teratogenic?

Answer 74

no structural maybe congenital heart defects (2%, vs 1%) craniosynostosis omphalocele ``` Newborn risks: mild, short-lived neonatal adaptation syndrome (NAS) Irritability Muscle rigidity/tremors Difficulty sleeping and feeding Heart rate disturbances Temperature irregularity Breathing problems ``` Maybe increased risk of persistent pulmonary hypertension incr risk of depression in 1st trimester kids of depressed mothers have incr risk of: depression disruptive social behavior changes in period of sensitivity for language

Question 75

Zofran/odansetrom - teratogenic?

Answer 75

possibly 2% risk of congenital heart disease FDA recently approved Diclegis® (doxylamine-pyridoxine) as the only medication approved for use for N&V of pregnancy

Question 76

methyl mercury - teratogen?

Answer 76

Minamata disease - Japan - severe neuro issues - microcephaly/cerebral palsy recommendation is for women to eat fish, but not too much, and not the wrong kind (not mackerel, swordfish, shark, tilefish).

Question 77

Radiation - teratogen - phenotype? - threshold for concern, in rads

Answer 77

5 rads (most procedures are

Question 78

Fluconazole - teratogen?

Answer 78

- if topical for vaginal yeast infection, then no problem - issue is if for Cocci infection (IV/oral) - increased risk of phenocopy of Antley-Bixler syndrome craniofacial, limb and cardiac anomalies

Question 79

anticonvulsant embryopathy

Answer 79

Phenytoin, trimethadione, carbamazepine, valproate, barbiturates ; increasingly used for bipolar hypertelorism, short, up-turned nose FINGERNAIL HYPOPLASIA ``` 6-15% risk: Meningomyelocele Oral clefts Congenital heart defects Limb defects ``` Developmental delay, esp w Valproic Acid Neurobehavioral differences were not seen in children exposed to lamotrigine

Question 80

Accutane -teratogen?

Answer 80

yes - vitamin A derivatives ``` Occurs in 20-30% of exposed babies Pattern of malformations CNS anomalies Ear anomalies Cardiovascular defects Thymus anomalies ``` Intellectual deficiency can be seen in 30-60% topical retinoids are OKAY

Question 81

Smoking - teratogen?

Answer 81

yes genetic interaction with TGF alpha - with clefts

Question 82

Morphine - teratogen - genexenvironment?

Answer 82

if moms are fast metabolizers, child gets much greater amounts of morphine through the breast milk. codeine is prescribed for pain after C-section.

Question 83

CMV

Answer 83

most are asymptomatic some: growth restriction, cerebral calcifications, ocular abnormalities and hepatosplenomegaly, esp HEARING LOSS, petichiae (BLUEBERRY MUFFIN BABY) If mom has primary infection, risk to child to get infection is 30-40%; lower if secondary infection (due to diff CMV strain) - socioeconomic effect - more high SES women are NOT immune of those not immune, ~3% will get infection, and 40% will pass it on. Of kids who get it, 10-15% will have clinically-aparent disease, and most (90%) will develop sequelae. Of those who do NOT have clinically-apparent disease, 10% will develop sequelae. if kid gets it, most likely will not be affected, but isn't without risk if doesn't exhibit infection.

Question 84

common cause of prenatal hearing loss

Answer 84

CMV infection

Question 85

blueberry muffin baby

Answer 85

CMV

Question 86

fetal alcohol syndrome

Answer 86

0.5-3 in 1,000 --> more common than Down syndrome ``` smooth philtrum short palpebral fissures short nose ptosis behavioral cognitive ```

Question 87

Pregnancy and Lactation Labeling Final Rule (12/3/2014)

Answer 87

The PLLR removes pregnancy letter categories – A, B, C, D and X and replaces it with an extensive narrative including sections on pregnancy, lactation, fertility and untreated maternal condition The PLLR requires the label to be updated when information becomes outdated. The Pregnancy subsection (8.1) includes information for a pregnancy exposure registry for the drug when one is available Takes effect on 6/30/15 with implementation expected to be complete in 3-5 years

Question 88

Things to ask about when considering teratogen risk assessment

Answer 88

Timing Dose Family, medical and pregnancy history Other exposures

Question 89

hCG levels, on average (not MoMs) - "normal" - with Down syndrome

Answer 89

"normal" - 0.8 | DS - 1.6 (2x!)

Question 90

source of cfDNA

Answer 90

``` placental cell apoptosis (10%) maternal DNA (90%) ```

Question 91

NIPT: reason why heavier women have higher levels of no-call results average = 3-5% no call >250 lbs = ___% >350 lbs = __%

Answer 91

fat has higher rates of apoptosis. More fat in mom = more maternal DNA in circulation, and it drowns out the fetal DNA by comparison average = 3-5% no call >250 lbs = 20% >350 lbs = 50%

Question 92

NIPT: | if no-call result is repeated, may not always get answer second time, either. which conditions is this associated with?

Answer 92

Trisomy 18 -- because presents with smaller placenta, thus less cfDNA of "fetus" Triploidy -- smaller placenta.

Question 93

NIPT: | reasons for false-positives

Answer 93

Contamination Unrecognized or vanishing twin Confined Placental mosaicism Low level maternal mosaicism (eg 45,X)

Question 94

Trisomy 21 - false positive rate on NIPT true positive / false positive = positive predictive value

Answer 94

0.5% true positive / false positive = positive predictive value 2 / 7 =

Question 95

the lower the a-priori risk of a chromosomal abnormality by NIPT, the __er the positive predictive value e.i., for the use of NIPT in a lower-risk population, the positive predictive value might go in which direction?

Answer 95

the LOWER the a-priori risk of a chromosomal abnormality by NIPT, the LOWER the positive predictive value = more false positives in low-risk population.

Question 96

NIPT: | how does residual risk of non-Tri13/18/21 chromosome abnormalities relate to a woman's age?

Answer 96

older women have much higher rates of chromosome abnormalities, but the proportion of these is much lower for women

Question 97

For Patients with Positive First Tri Screen Residual Risk of Chromosome Abnormal after Normal NIPT

Answer 97

1 in 52

Question 98

Miller-Dieker | - which prominent finding?

Answer 98

Lissencephaly 17p13 del

Question 99

congenital heart defects: | if karyotype normal, what percent is attributable to a CNV detectable by microarray that is NOT 22q

Answer 99

63% of CHD are due to CNVs besides 22q some say microarray should be first tier test for congenital heart defects

Question 100

most CNVs are NOT incompletely penetrant, but have ___

Answer 100

variable expressivity.

Question 101

Cytogenetic abnormalites occur in approximately __ of pregnancies Whole chromosome abnormalities ? Microdeletions and duplications ?

Answer 101

Cytogenetic abnormalites occur in approximately 2% of pregnancies Whole chromosome abnormalities 0.6% Microdeletions and duplications 1.3 %