How does the mode of inheritance of a genetic condition influence families

While the mode of inheritance of a genetic condition has long been considered to have not only medical but also psychological consequences for families, this supposition has never been tested. The X-linked (XL) and autosomal recessive (AR) forms of chronic granulomatous disease (CGD) provide a model for comparing the effect of mode of inheritance while controlling for differences in phenotype. To determine the influence of mode of inheritance on parents', siblings', and patients' (1) understanding of inheritance and reproductive risk, (2) concern about risk to future family members, (3) feelings of guilt and blame, (4) feelings of stigmatization, and (5) attitudes toward carrier testing of minors, I surveyed 112 members of 51 families (59% response) with CGD. Ninety-six members of 51 families (49% response) with Duchenne/Becker muscular dystrophy (XL) or spinal muscular atrophy types II/III (AR) were also studied. Members of XL families understood the mode of inheritance (p < 0.001) and their reproductive risks (p < 0.01) better than AR family-members. Except for mothers, AR family members were as worried about the risks to future generations as their XL counterparts. Most XL mothers felt guilty about, and blamed themselves for, their child's disease. XL mothers were more likely to feel guilty (p < 0.01) and blame themselves (p < 0.001) than were AR mothers or fathers of either condition (p < 0.001). Conversely, XL fathers were more likely than XL mothers (p < 0.001) or AR fathers (p < 0.05) to admit to blaming their child's other biological parent for the condition. XL family members were also more likely to consider learning one was a carrier stigmatizing (p < 0.05). Finally, XL family-members were somewhat more likely to favor carrier testing for a three (p < 0.05) and thirteen year-old (p < 0.01) daughter. This study has implications for improving genetic counseling for families of and individuals with childhood-onset X-linked and autosomal recessive conditions. Counseling should assist families in understanding, and coping with, both the medical and psychological implications of the inheritance pattern. Particular attention should be given to (1) issues of guilt and blame in XL families and (2) understanding of reproductive risks in AR families.