Sibling knowledge and attitudes toward carrier testing for X-linked severe combined immunodeficiency. J.M. Puck1, J.H. Fanos2, J. Davis1. 1) NHGRI/NIH, Bethesda, MD; 2) California Pacific Medical Center Research Institute, San Francisco, CA.
X-linked severe combined immunodeficiency (XSCID) is the most common genetic form of SCID, a rare (1/50,000 births) disease with profoundly impaired cellular and humoral immunity. Popularized as the disease of David the Bubble Boy, isolated from birth in a germ-free environment, SCID was previously fatal, but now is usually successfully treated by bone marrow transplantation. Mapping of XSCID in 1985, and identification of the disease gene, IL2RG, in 1993, have made possible patient and carrier diagnosis. We assessed understanding of the genetics of XSCID and attitudes toward carrier testing in siblings recruited from families in which a proband had previously enrolled in our linkage or mutation detection protocols and been proven to have XSCID. 37 female and 3 male adult siblings completed a questionnaire and semi-structured interview. Overall knowledge of the genetics of XSCID was excellent, with 14 of 16 questions answered correctly by >75% of subjects. Questions frequently missed: only 49% knew all daughters of an affected boy would be carriers, and 53% were unaware that spontaneous mutation for XSCID was possible. Of interest, siblings from kindreds with a documented spontaneous mutation were less likely to answer this question correctly than those in multi-generational XSCID kindreds (p=0.01). 93% of our sibling group believed daughters should be tested for XSCID carrier status. 89% would prefer to have their own daughter tested prior to reaching 18 years (M=9, Median=12); 34% would test at birth. 89% would disclose carrier results to their daughter before her 18th birthday (preferred disclosure age M=12 years, Median=12); 51% would disclose prior to adolescence. Preference for carrier testing before adulthood reflected the subjects' desire to have parents impart knowledge at what they felt was an optimal time to minimize childrens misconceptions. We recommend that genetic counseling for XSCID include children in age-appropriate discussions and help parents weigh the benefits of early testing and disclosure vs. the potential harm of loss of child autonomy.