GONADAL (OVARIAN) DYSGENESIS IN 46,XX INDIVIDUALS - FREQUENCY OF THE AUTOSOMAL RECESSIVE FORM

Gonadal (ovarian) dysgenesis with normal chromosomes (46,XX) clearly i s a heterogeneous condition. In some forms, the defect is restricted t o the gonads, whereas other affected females show neurosensory hearing loss (Perrault syndrome). In another form, brothers may have germ cel l aplasia [Granat et al., Fertil Steril 1983; 40:215-219]. Nongenetic causes exist as well. To elucidate the proportion of XX gonadal (ovari an) dysgenesis due to autosomal recessive genes, we analyzed published (N = 17) and unpublished (N = 8) families having at least two female offspring. Analysis was restricted to cases in whom ovarian failure wa s documented by the presence of streak ovaries (published cases) or el evated gonadotropins (unpublished cases). We reasoned that the closer to that segregation ratio expected for an autosomal recessive trait (0 .25), the lower the frequency of nongenetic forms. Segregation analysi s utilized standard correction for single ascertainment, with only fem ales included in the preliminary analysis. The segregation ratio estim ate was 0.16. Our results suggest that many 46,XX females with gonadal (ovarian) dysgenesis represent a disorder segregating as an autosomal recessive trait, placing sisters of these cases at a 25% risk for thi s disorder. (C) 1996 Wiley-Liss, Inc.