Screening and Multi-factorial Inheritance/Complex disorders Flashcards
The % empiric recurrence risk for a multifactorial/complex trait in
- First degree relative
- Second degree relative
- Third degree relative
- 3.2
- 0.5
- 0.17
The recurrance risk in a first degree relative is approx the _____ ________ of the population incidence
- Square root
Traits with male sex bias include (5)
- Pyloric stenosis
- Hirsprung Disease
- CL +/- CP
- Legg Calves Perthe Disease
- Club foot
Traits with a female sex bias (3)
- Congenital hip dislocation
- Cleft palate
- Open neural tube defects
In multifactorial traits most affected children have ______parents
unaffected
In multifactorial traits recurrence risk ________ with the number of affected children in the family
increases
Recurrence risk _____ with the severity of the defect, in multifactorial defects
increases
If a population has a higher incidence of a disorder, the recurrance risk is _______ in that population
higher
Consanguinity ________ increases the risk for an affected child in multifactorial traits
slightly
If two sexes have a different probability of being affected, the _____________ if affected, is the most likely to produce an affected offspring
least likely sex
A disorder affects males twice as often as females. Which offspring has the highest risk of being affected?
The son of affected female
Definition: number of affected individuals** who test positive for the disease out of the total number of **affected individuals
Sensitivity
Definition: the number of unaffected individuals** who have a **negative test** result out of the total number of **unaffected individuals
Specificity
1-Specificity
False Positive Rate: the fraction of unaffected individuals who screened positive
1-sensitivity
False negative rate: number of affected individuals with a negative screen
What happens when we screen in a population with decrease disease incidence?
You will have a decrease in what values
- PPV
- True positives
- False negatives
What happens when we screen in a population with decrease disease incidence?
You will have a increase in what values
- NPV
- True negatives
- False positives
Evevation of the following on newborn screen is suggestive of what condition?
C0/C16+C18
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
Evevation of the following on newborn screen is suggestive of what condition?
C16 and or C18:1
CPT 2/ CACT deficiency
Carnitine Palmitoyltransferase 2 deficiency
Evevation of the following on newborn screen is suggestive of what condition?
C4;C5
Glutaric acid 2/ Ethylmalonic encephalopathy
MADD- multiple acyl-CoA dehydrogenase deficiency
Evevation of the following on newborn screen is suggestive of what condition?
C16-OH +/- C18:1-OH
Long Chain Hydroxyacyl-CoA Dehydrogenase deficiency (LCHAD)
Trifunctional Protien D (TFP)
Evevation of the following on newborn screen is suggestive of what condition?
C8; C6, C10
Mediun chain AcylCoA Dehydrogenase deficiency (MCAD)
Evevation of the following on newborn screen is suggestive of what condition?
C14:1
Very long chain acylCoA dehydrogenase Deficiency (VLCAD)
Newborn Screening
May or may not be detected on acylcarnitine analysis C5-OH
Clinical features: Neurological (Seizures), dermatitis, hypotonia, alopecia, conjuctivitis
Condition and Treatment?
Biotinidase Deficiency
Tx: Biotin
Newoborn Screening
Organic acid analyte
Glutaric Acidemia type 1
C5-DC
Newoborn Screening
Organic acid analyte
Isovalaric acididemia
C5
Newoborn Screening
Organic acid analyte
Malonic Acidemia
C3-DC
Newoborn Screening
Organic acid analyte
Methylmalonic and Proprionic aciduria
C3
Newborn Screening
Low GALT
Elevated galactose-1 phosphate or Galactose
What symptoms would you expect in an untreated infant
Classic Galactosemia
- Feeding difficulty
- Failure to thrive
- Liver Failure
- Bleeding
- E.Coli sepsis
Maternal serum screening
only marker used to calculate NTD risk
AFP
Maternal Serum Screening
Weighted most heavily in calculated Down Syndrome Risk
Human Chorionic Gonadotropin (hCG)
Maternal Serum Screening Pattern
High MSAFP
Normal hCG
Normal uE3
Normal Inhibin-A
Neural Tube Defect/Anencephaly
Maternal Serum Screening Pattern
Low MSAFP
High hCG
Low uE3
High Inhibin-A
Down Syndrome
Maternal Serum Screening Pattern
Low MSAFP
Low hCG
Low uE3
Low Inhibin-A
Trisomy 18
Maternal Serum Screening Pattern
Normal MSAFP
Normal hCG
Very low/Undetectable uE3
Normal Inhibin-A
Steroid Sulphatase Deficiency/ Smith Lemil Opitz
For MSAFP
3-4.9 MoM
the risk for poor outcome is
about 41%
For MSAFP
>5MoM
the risk for poor outcome is?
about 91%
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
2.5 MoM
which translated to about 2-3% of woman screened
of these about 10% will have a NTD or ventral wall defect
Reasons for false positive NIPs
- Placental mosaicism
- Vanishing twin
- Maternal mosaism
- Maternal malignancy
Reason for failed NIPs
- Low fetal DNA (Can be a sign of aneuploidy)
- High maternal BMI
- Early gestational age (should not be performed beofre 9-10 wks)
