The female carrier of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is an X-linked recessive disorder, affecting only males and transmitted by females, who have a 50%1 risk of an affected son or a carrier daughter. The incidence has been estimated at between one in 3000 and one in 5000 male births,' but not all the mothers of affected infants are carriers; a substantial proportion of cases will represent new mutations. According to Haldane,2 the mutation rate for a potentially lethal X-linked condition in which the biological fitness (fertility) of affected males is practically zero would be one-third. Estimates based on population studies have produced a similarly high figure.3-5 If, then, one-third of the mothers of affected infants are not carriers the investigation of the carrier state and genetic counselling are vitally important for the families concerned. The first essential step in genetic counselling must always be to verify the diagnosis in the index case. Next, a detailed family tree should be constructed before investigation of the possible carrier is begun. A genetically definite or obligate carrier is a woman with an affected son and an additional affected male relative; all other female relatives are possible carriers. The creatine kinase test is the most reliable for detecting carriers. The serum activity of the enzyme is grossly raised in patients with Duchenne dystrophy, and raised to a mild-tomoderate extent in some but not all female carriers of the gene. Several studies have shown the proportion of genetically obligate carriers with definitely raised creatine kinase activities to be about two-thirds.7-9 Since creatine kinase activity is normal in about a third of definite carriers it clearly does not exclude the carrier state. An accurate estimate of the statistical risk that a woman with a normal creatine kinase activity is a carrier can be made from the actual activity of the creatine kinase, on the basis of the distribution curves in normal controls and in obligate carriers and the application of Bayesian theory, which takes account both of the antecedent family history and of the creatine kinase activity of the person at risk and of other female relatives.'0 Follow-up studies of families counselled in this way have verified the validity of this approach."-'3 The creatine kinase activity can be spuriously high after vigorous exercise and it drops during pregnancy.'4 15 Genetic counselling requires the combined skills of the