Prenatal Diagnosis and Genetic Counseling of Cystic Fibrosis

The number of DNA markers at the chromosome 7‐locus of the putative CF gene has markedly increased in recent years, also as a result of intensive research into the possible “candidate” gene. In studies of families with one or more affected children, 97.5 % of families are now fully informative, allowing a prenatal diagnosis by chorionic villus sampling in the 10th week and DNA‐analysis, which will usually give now a diagnosis with a remaining risk of less than 1 %. The microvillar enzyme test in amniotic fluid after amniocentesis in the 18th week will remain an alternative for couples who have a high prior risk, but are either not informative at DNA analysis, or where no information on a (deceased) index case (previous affected child) is available. The risk for a wrong classification is in the order of a few percent (in a 1:4 prior risk case) and careful discussion of the limitations are needed when this test is applied to cases with a lower prior risk. The linkage disequilibrium established for a number of RFLP's (Restriction Fragment Length Polymorphisms), as detected by various probes and various restriction enzymes around the CF locus has opened the possibility to refine the risk estimation of heterozygosity for individuals outside families with CF‐affected children. The presence of certain haplotypes may change the risk for being CF heterozygote from ±1:7 to 1:250, as compared to a population risk of ±1: 25. Such a risk estimation seems insufficient for carrier detection at the population level, but may be useful in specific situations, as in selection of a sperm donor for those CF parents who opt for artificial insemination by donor sperm, etc. The possible genetic heterogeneity of CF is discussed recently, and future work is needed to see if CF with meconium ileus is genetically different (with a higher risk of recurrence) from other forms of the disorder.