SUN-208 Rare Case of 47XXY/46XX Mosaic Klinefelter Syndrome

Abstract

Introduction: Klinefelter syndrome (KS) is the most common X chromosome abnormality and genetic cause of male infertility. Nondisjunction of paired X chromosomes during meiosis or gametogenesis gives rise to the karyotype 47XXY seen in 80 % of cases. The most common form of mosaicism results from post-fertilization nondisjunction of the XXY zygote in two cell lines 47XXY/46XY in 15-20 % of KS. The 47XXY/46XX mosaic form is very rare with only 20-25 cases described in the literature to date. Phenotype varies with distribution of the two cell lineages in developing embryo tissues, including KS male, true hermaphroditism, ovarian hypoplasia and normal female. Only 10 cases have been reported of 47XXY/46XX mosaic KS male phenotype . Our case is the 11th. Case: A 39 year old male presented with fatigue, weight gain, poor concentration and loss of libido. He reported no secondary sexual development during puberty, including hair, muscle mass, penis and testicles, and minimal erections. On exam, both testes were less than 2 cm with a normal penis. He had abdominal obesity, reduced muscle mass, and gynecomastia, as well as male pattern frontal baldness. Total testosterone (T) was 125 ng/dl (250-1100), Free T was 16 ng/dl (46-224), albumin was 3.9, FSH was 25 mIU/ml, and LH was 15.9 mIU/ml. Chromosome analysis: 25/30 (83%) cells 47XXY and 5/30 (17 %) cells 46XX. FISH study on 100 peripheral blood cells showed 87 % 47XXY and 14 % 46XX. The patient did not desire fertility and started testosterone replacement. Conclusion: Our case demonstrated the common features of 47XXY/46XX mosaic KS, including small testes, gynecomastia, hypergondotropic hypogonadism, and normal IQ. Interestingly, our patient had male pattern baldness, which was also common in his family. The average age of diagnosis for cases reported to date was 12-62 years, similar to ours, suggesting a delay in diagnosis, as can occur in many KS cases. Distribution of cell lines can vary between different tissues, but the presence of a Y chromosome in the gonad determines the phenotype. Mediastinal germ cell tumor, testicular teratoma, and radioulnar synostosis have been noted in 3 cases but not in this case. Mosaic cases tend to be more androgenic, and are more likely to have spermatogenesis than non-mosaic KS. This along with the failure to detect the 46XX cell line in routine blood cytogenetic tests (as opposed to gonadal tissue) is the reason for delayed detection in many cases. KS mosaicism should be considered in all cases of male infertility.