Friedman developed an equation to predict the recurrence risk for an autosomal dominant condition when both parents are clinically unaffected.
The differential diagnosis for the situation of an affected child with unaffected parents:
(1) new mutation
(2) autosomal dominant condition with incomplete penetrance and with reproductive fitness of the affected person close to normal
If the child is affected due to a new mutation, then the risk of recurrence is very low. If the affected child has an autosomal dominant condition inherited from a clinically normal parent, then the recurrence risk is higher.
Conditions for Friedman's equation:
(1) autosomal dominant condition
(2) both parents clinically unaffected
(3) calculating the risk for the sibling of an affected child
(4) does not integrate the condition of having normal siblings in addition to the affected child
risk for sibling =
= ((penetrance) * (1 - (penetrance)) / (2 * (2 - (penetrance) - (fitness of carrier genotype)))
• The fitness of the carrier is that for all heterozygotes, regardless of the phenotype.
• penetrance and fitness are decimal fractions from 0 to 1.
• According to Table 1, page 70, only cases where (1 - (fitness)) < (penetrance) are relevant, since the proportion lost to selection cannot be greater than the penetrance.
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