Screening and Multi-factorial Inheritance/Complex disorders

Question 1

The % empiric recurrence risk for a multifactorial/complex trait in

• First degree relative
• Second degree relative
• Third degree relative

Answer 1

• 3.2
• 0.5
• 0.17

Question 2

The recurrance risk in a first degree relative is approx the _____ ________ of the population incidence

Answer 2

• Square root

Question 3

Traits with male sex bias include (5)

Answer 3

1. Pyloric stenosis
2. Hirsprung Disease
3. CL +/- CP
4. Legg Calves Perthe Disease
5. Club foot

Question 4

Traits with a female sex bias (3)

Answer 4

1. Congenital hip dislocation
2. Cleft palate
3. Open neural tube defects

Question 5

In multifactorial traits most affected children have ______parents

Answer 5

unaffected

Question 6

In multifactorial traits recurrence risk ________ with the number of affected children in the family

Answer 6

increases

Question 7

Recurrence risk _____ with the severity of the defect, in multifactorial defects

Answer 7

increases

Question 8

If a population has a higher incidence of a disorder, the recurrance risk is _______ in that population

Answer 8

higher

Question 9

Consanguinity ________ increases the risk for an affected child in multifactorial traits

Answer 9

slightly

Question 10

If two sexes have a different probability of being affected, the _____________ if affected, is the most likely to produce an affected offspring

Answer 10

least likely sex

Question 11

A disorder affects males twice as often as females. Which offspring has the highest risk of being affected?

Answer 11

The son of affected female

Question 12

Definition: number of affected individuals** who test positive for the disease out of the total number of **affected individuals

Answer 12

Sensitivity

Question 13

Definition: the number of unaffected individuals** who have a **negative test** result out of the total number of **unaffected individuals

Answer 13

Specificity

Question 14

1-Specificity

Answer 14

False Positive Rate: the fraction of unaffected individuals who screened positive

Question 15

1-sensitivity

Answer 15

False negative rate: number of affected individuals with a negative screen

Question 16

What happens when we screen in a population with decrease disease incidence?

You will have a decrease in what values

Answer 16

• PPV
• True positives
• False negatives

Question 17

What happens when we screen in a population with decrease disease incidence?

You will have a increase in what values

Answer 17

• NPV
• True negatives
• False positives

Question 18

Evevation of the following on newborn screen is suggestive of what condition?

C0/C16+C18

Answer 18

CPT 1 deficiency

carnitine palmitoyl transferase 1 deficiency

prevents the fatty acid carnitine-acylcarnitine linkage required to transport fatty acids into the mitochondria

this results in accumulation of free carnitine (C0) and prevents the fatty acid oxidation response neccessary to generate energy during fasting and increased energy needs

Question 19

Evevation of the following on newborn screen is suggestive of what condition?

C16 and or C18:1

Answer 19

CPT 2/ CACT deficiency

Carnitine Palmitoyltransferase 2 deficiency

Question 20

Evevation of the following on newborn screen is suggestive of what condition?

C4;C5

Answer 20

Glutaric acid 2/ Ethylmalonic encephalopathy

MADD- multiple acyl-CoA dehydrogenase deficiency

Question 21

Evevation of the following on newborn screen is suggestive of what condition?

C16-OH +/- C18:1-OH

Answer 21

Long Chain Hydroxyacyl-CoA Dehydrogenase deficiency (LCHAD)

Trifunctional Protien D (TFP)

Question 22

Evevation of the following on newborn screen is suggestive of what condition?

C8; C6, C10

Answer 22

Mediun chain AcylCoA Dehydrogenase deficiency (MCAD)

Question 23

Evevation of the following on newborn screen is suggestive of what condition?

C14:1

Answer 23

Very long chain acylCoA dehydrogenase Deficiency (VLCAD)

Question 24

Newborn Screening

May or may not be detected on acylcarnitine analysis C5-OH

Clinical features: Neurological (Seizures), dermatitis, hypotonia, alopecia, conjuctivitis

Condition and Treatment?

Answer 24

Biotinidase Deficiency

Tx: Biotin

Question 25

Newoborn Screening Organic acid analyte Glutaric Acidemia type 1

Answer 25

C5-DC

Question 26

Newoborn Screening Organic acid analyte Isovalaric acididemia

Answer 26

C5

Question 27

Newoborn Screening Organic acid analyte Malonic Acidemia

Answer 27

C3-DC

Question 28

Newoborn Screening Organic acid analyte Methylmalonic and Proprionic aciduria

Answer 28

C3

Question 29

Newborn Screening Low GALT Elevated galactose-1 phosphate or Galactose What symptoms would you expect in an **untreated infant**

Answer 29

Classic Galactosemia * Feeding difficulty * Failure to thrive * Liver Failure * Bleeding * E.Coli sepsis

Question 30

Maternal serum screening only marker used to calculate NTD risk

Answer 30

AFP

Question 31

Maternal Serum Screening Weighted most heavily in calculated Down Syndrome Risk

Answer 31

Human Chorionic Gonadotropin (hCG)

Question 32

Maternal Serum Screening Pattern High MSAFP Normal hCG Normal uE3 Normal Inhibin-A

Answer 32

Neural Tube Defect/Anencephaly

Question 33

Maternal Serum Screening Pattern Low MSAFP High hCG Low uE3 High Inhibin-A

Answer 33

Down Syndrome

Question 34

Maternal Serum Screening Pattern Low MSAFP Low hCG Low uE3 Low Inhibin-A

Answer 34

Trisomy 18

Question 35

Maternal Serum Screening Pattern Normal MSAFP Normal hCG Very low/Undetectable uE3 Normal Inhibin-A

Answer 35

Steroid Sulphatase Deficiency/ Smith Lemil Opitz

Question 36

For MSAFP 3-4.9 MoM the risk for poor outcome is

Answer 36

about 41%

Question 37

For MSAFP \>5MoM the risk for poor outcome is?

Answer 37

about 91%

Question 38

For MSAFP what MoM value is mostle used for screen positive individuals and of these woman screened positive what % will have a NTD or open abdominal wall defect

Answer 38

2.5 MoM which translated to about 2-3% of woman screened of these about 10% will have a NTD or ventral wall defect

Question 39

Reasons for false positive NIPs

Answer 39

* Placental mosaicism * Vanishing twin * Maternal mosaism * Maternal malignancy

Question 40

Reason for failed NIPs

Answer 40

* Low fetal DNA (Can be a sign of aneuploidy) * High maternal BMI * Early gestational age (should not be performed beofre 9-10 wks)