Abstract

Between January 1975 and January 1980 we counselled 214 possible or obligatory carriers of haemophilia A in an attempt to provide the counsel they needed and to determine the utility of a probabilistic method of assigning the heterozygous genotype (carrier detection). We found the method of assignment to be quick and easy to use, and the single output (the final probability favouring carriership P(C)) to be understood by most counsellees. The final probabilities obtained were either very high or very low in 80% of the women, which allowed us to give clear counsel in four instances in five. The final probabilities could also be used to relate Mendelian expectation to observation within each of three subsets of women (18 mothers of sporadic haemophiliacs, 78 sisters, and 62 more distant relatives), while the aberrant likelihood ratios of 6/36 (17%) of the obligatory carriers provided an estimate of the false negative diagnostic rate owing to lyonisation. There was no significant age effect on VIII:C or VIIIR:Ag levels of obligatory carriers, and the VIII:C levels of the obligatory carriers who had received the gene from their fathers did not differ from those of the obligatory carriers who had received the gene from their mothers. The ratios of high:low probabilities among the sisters and distant relatives of haemophiliacs conformed to genetic expectation, while the ratio among mothers of sporadic haemophiliacs suggested that their expectations of carriership were greater than 80%.

Twenty of the 214 counsellees (9%) were pregnant on the first visit, and 13 of those with low P(C)s (0·0-0·33) went to term and delivered 11 non-haemophilic children. Four with P(C)s between 0·50 and 1·00 requested amniocenteses, and one male was aborted. Three who were obligatory carriers also requested amniocentesis which led to the abortion of a second male.

Seven women who were assessed before pregnancy and found to have high P(C)s returned after becoming pregnant. All requested amniocentesis (one twice) and fetoscopy was requested for six of the seven males discovered, one male having been aborted before fetoscopy became available. Of the six males who were fetoscoped, three normal males reached term, one normal male was born prematurely, and one haemophilic male and one normal male did not survive fetoscopy.