A highly rare female phenotype with complex chromosomal mosaicism: 46,XY/45,X/46,X,r(Y)

Mixed gonadal dysgenesis is characterized by abnormal genital appearance and chromosomal mosaicism. A wide spectrum of clinical manifestations can occur, ranging from females (with or without Turner syndrome) to phenotypically normal males with some degree of genital ambiguity. In this context, uncommon mosaic karyotypes are associated with distinctive phenotypic characteristics. Here, we present the case of an 18-year-old girl with primary amenorrhea, delayed puberty, and a rare mosaic karyotype pattern. Clinical data were collected, and karyotyping was performed on peripheral blood samples. Polymerase chain reaction amplification for the sex-determining region Y protein (SRY) gene was also conducted. The patient presented with delayed puberty and primary amenorrhea. Her hormonal profile was consistent with hypergonadotropic hypogonadism. Pelvic magnetic resonance imaging revealed a small uterus. Echocardiography identified the presence of a bicuspid aortic valve. Karyotyping demonstrated a 46,XY/45,X/46,X,r(Y) pattern, indicating mosaicism for monosomy X and two cell lines: 45,X and 46,X,r(Y). The SRY gene was detected. Gonadal pathological investigation confirmed streak gonads consistent with gonadal dysgenesis and evidence of gonadoblastoma. Complicated cases with mosaic chromosomal patterns can exhibit a wide range of phenotypic features, from apparently normal males with variable external genitalia to females with or without characteristics of Turner syndrome. These phenotypic discrepancies are not directly related to the number of mosaic cells or the specific location of Y chromosome breakage. Therefore, in cases of primary amenorrhea with genotype-phenotype discrepancies, a multidisciplinary approach is essential to guide appropriate sex determination and management.