MF Inheritance

Question 1

what is multifactorial inheritance?

Answer 1

traits determined by combo of multiple factors (genes, environment, number and impact vart, threshold effect)

Question 2

how might MF inheritance appear in an FHx?

Answer 2

clustering, no clear pattern

Question 3

how common are multifactorial conditions?

Answer 3

5% incidence @ birth, 60% population prevalence

Question 4

what are some common congenital MF conditions? adult-onset? gen pop exs?

Answer 4

congenital: CL/P, ONTds, CHD
adult: diabetes, heart disease, epilepsy, affective disorders
gen: height, intelligence, blood pressure

Question 5

what types of genetic changes are invovled in MF inheritance/conditions? environmental factors?

Answer 5

susceptibilty genes, modifiers, epigenetic modification

diet, exercise, teratogens, infections, smoking, trauma, stress, pollutants

Question 6

what are continuous traits (MF)?

Answer 6

quantitative trait, follow bell-shaped distribution (i.e. height)

Question 7

what are discontinuous traits?

Answer 7

qualitative traits (threshold effect, trait is absent or present - CHD)

Question 8

what are some complications with studying of MF conditions?

Answer 8

often more difficutls due to contribution environmental factors

predictive testing is often not possible

testing may determine that is an increased susceptibility

studies strive to determine heritability

Question 9

how can twin studies help us understand qual/discontinuous traits and their etiology? any limits?

what role do family studies play?

Answer 9

the difference in concordance btwn MZ and DZ twins supports genetic contribution to etiology

disease concordance <100 in MZ or 100% in DZ twins suggests role of nongenetic factors in etiology

limits: usually share the same environment
family: generates relative risk or risk ratio compared to risk in gen pop

Question 10

what model can help explain the combined effect of genetic and environmental factors and explain the presence of discontinuous traits?

Answer 10

threshold model

Question 11

where do recurrence risks for MF come from? what is the generally accepted risk? is this always the case? if not, ex?

Answer 11

empiric data

2-5%

nope - look it up!! varies based on condition, features, and severity of presentation, FHx, and presence/absence of other risk factors

i.e. unilateral cleft lip vs. bilateral cleft lip & palate (higher)

Question 12

how do we generally think about recurrence risks (for MF) and adjust them?

Answer 12

• depends of # of affected relatives and degree of relatedness
• RR to FDR is greater than gen. pop (risk drops sharply for more distantly related individuals)
• RR increases proportionately to the number of affected individuals in a family
• RR typically higher if disorder is in the more severe range
• higher if proband is of the less commonly affected sex
• quoted as avg (true risk in family may be higher or lower)
• an vary from one pop to another
• understanding RR in context of background risk and other known contributing factors

Question 13

pyloric stenosis more commonly impacts what sex? where is a good place to start when looking for MF risks?

Answer 13

male

Harper’s

Question 14

who is considered you index patient when looking at MF inheritance and risks?

Answer 14

the affected person

Question 15

what should we consider when counseling about MF conditions?

Answer 15

• RR are empiric (based on populations, not individuals)
• depends on disease incidence
• 1/2 sibs are SDR (not FDR)
• consider MF etiology when developing a DDx
• discuss background risks