Calculation of Recurrence Risks for Heterogeneous Genetic Disorders

We present general formulae for several common situations in the genetic counseling of heterogeneous disorders. The occurrence or not of parental consanguinity is taken into account, since it distorts significantly the prior probabilities favoring the different mechanisms. Nonsyndromic deafness is used as a numerical application, since it can be produced by any type of monogenic inheritance and can be mixed with variable proportions of environmental cases. Recurrence risks are calculated including or not including environmental factors in the origin of the defect. In underdeveloped c ountries t he p roportion o f environmentally determined cases of deafness is significantly higher than in firstworld countries. Therefore, when environmental c auses c annot b e e xcluded, recurrence risks are always higher in developed than in developing countries. On average, when parental consanguinity is present there is a significant increase in recurrence risks for deafness, whether environmental factors are included or not. Am. J. Med.