Week 2 Borch

Question 1

What is the use of oligo arrays?

Answer 1

Can probe down to the level of resolution of a SNP (ie SNP array, extremely high density oligo array). Can use relative strength of signal to detect copy number.
Oligo array – provides copy number
SNP array (ie, extremely high density oligo array) – provides code info

Question 2

Differentiate Analytical Validity, Clinical Validity, and Clinical Utility

Answer 2

Analytical validity – accuracy, reliability
Clinical validity – degree of true association between having mutation and increased risk relative to population
Clinical Utility – the ability of the test results to improve patient outcomes

Question 3

Minor malformation

Answer 3

<4% population, but does not require intervention

Question 4

Major malformation

Answer 4

has significant medical consequences, requires intervention

Question 5

Malformation

Answer 5

did not form correctly

Question 6

Deformation

Answer 6

formed correctly, but outside forces altered shape, etc

Question 7

Disruption

Answer 7

formed correctly, but outside forces destroyed it partially or completely (ie amniotic bands)

Question 8

Malformation syndrome

Answer 8

group that “goes together,” due to single underlying cause

Question 9

Malformation sequence

Answer 9

single malformed structure causing one or more secondary malformations as a consequence

Question 10

Omphaloceole

Answer 10

abdominal wall malformation causing extrusion of viscera into peritoneum covered sack associated with ombilicus

Question 11

Gastroschisis

Answer 11

abdominal wall malformation causing extrusion of viscera without any membranous covering, without association with ombilicus

Question 12

Triploidy

Answer 12

Microsomia (small body, head is normal size)
Syndactyly of 3rd and 4th digits
Cystic placenta

Question 13

Trisomy 21

Answer 13

Face/head: upslanting palpebral fissures, epicanthal folds, hyperglossia (big tongue), flat occiput (brachycephaly), brushfield spots in eyes
Body: redundant neck skin
Hands: single palmar creases, pinky clinodactyly
General: Hypotonia

Question 14

What is the leading cause of death in Down Syndrome babies <1 y/o?

Answer 14

Cardiac Complications

Question 15

Trisomy 18

Answer 15

Face/Head – prominent occiput, micrognathia
Extremities – overlapping digits, rocker bottom feet
Body – omphaloceole is common

Question 16

Trisomy 13

Answer 16

Face/Head: scalp defects, micropthalmia (and/or hypotelorism), cleft palate defects, holopresencephaly
Other: polydactyly, rockerbottom feet

Question 17

Turner Syndrome

Answer 17

Single X chromosome
General: Small stature, gonadal dysgenesis
Body: Neck webbing, shield chest
Cardiac and renal abnormalities (horseshoe kidney)
Intellectual impairment NOT a prominent feature

Question 18

Klinefelter Syndrome

Answer 18

XXY phenotype
Phenotype is general “feminization” of the male form
Tall, gynecomastia (growth of breast tissue), microorchidism (small testes)
Intellectual impairment more common

Question 19

XYY

Answer 19

Phenotype is variant of normal; maybe taller

Aggressive/antisocial behavioral tendencies???

Question 20

XXX

Answer 20

Phenotypic variant of normal; taller, with some fertility problems
Possibly some learning/intellectual problems

Question 21

Cri du Chat

Answer 21

5p deletion
Shrill cry
Microcephaly
Downslanting palpebral fissures
Hypertelorism
Mental retardation

Question 22

Wolf-Hirshorn

Answer 22

4p deletion
Frontal bossing (Roman Helmet)
Micrognathia
Hypospadius
Cardiac defects
Extreme MR
(Wolf-Hirshorn – I think of a Germanic warrior, covered in a Wolf pelt with a Horned Viking helmet fighting a Roman Centurian (frontal bossing))

Question 23

Prader-Willi

Answer 23

Loss of expression of PATERNAL allele of ch. 15 (parental imprinting)
Neonatal hypotonia
Propensity to morbid obesity
Mental retardation
Small gonads/genitals
(Phenotype ~ Little Billy from the Gary Larson cartoons)

Question 24

Angelman

Answer 24

Loss of expression of MATERNAL allele of ch. 15 (parental imprinting)
Happy puppet on strings
Seizures and jerky ataxic movements
Severe MR

Question 25

Williams Syndrome

Answer 25

7q deletion Uncanny musical propensity (at expense of diminished mathematical/spatial ability) “Elfin” facies Cocktail party personality

Question 26

Describe the typical findings in the 22q deletion syndromes.

Answer 26

CATCH 22 ``` Cardiac defects Abnormal Facies Thymic Aplasia Cleft Lip Hypocalcemia ``` Why? Because 22q is important for pharyngeal arch development, note these structures are all from pharyngeal arches.

Question 27

DiGeorge Syndrome

Answer 27

22q deletion CATCH 22 symptoms Small at birth

Question 28

Velocardiofacial Syndrome

Answer 28

22q deletion CATCH 22 symptoms More common to have cleft palate abnormalities Broad nose

Question 29

Miller-Dieker

Answer 29

17p deletion Thin upper lip Lissencephaly (poor brain formation – no gyri and sulci, just smooth cortex) Severe MR

Question 30

What is the big disadvantage of a Microarray analysis?

Answer 30

Balanced translocations are NOT detected

Question 31

In general, when do we suggest diagnostic testing?

Answer 31

When the risk of significant abnormalities exceeds the risk of the procedure. Note: this may not be 35 y/o.

Question 32

Give the typical malformations/defects seen in the following maternal health conditions: Diabetes Mellitus Seizure disorders Congenital Adrenal Hyperplasia

Answer 32

DM ONTDs, Sacral agenesis Seizure disorders ONTDs (not accounted for solely by meds) Congenital Adrenal Hyperplasia virilization

Question 33

First Trimester screening tests for Down Syndrome?

Answer 33

Nuchal translucency US | Beta HCG, PAPP-A

Question 34

Second Trimester screening tests for Down syndrome?

Answer 34

``` Quad screen: AFP Beta HCG Unconjugated Estriol 3 Inhibin A (note: these will all be decreased in other trisomies) ```

Question 35

What is the role of cell-free fetal DNA in testing?

Answer 35

Useful, but not yet gold standard. | On a test, go with the gold standard (1st and 2nd trimester screenings)