Klinefelter Syndrome with Azoospermia：Identification of a Neocentromic Y Chromosome with No Detectable DYZ3 Centromeric Sequence

Background Individuals with rare cytogenetic variants have contributed to our understanding of the genetics of sex chromosome and its disorders. Here, we report on a 23 years old man with a de novo 47,XX,+mar.ish der(Y)neo(Y)(pter-->p11.2::q11.23-->neo-->q11.23-->qter)(DYZ3-,SRY+,WCPY+) chromosome complement, accompanying with azoospermia and some of other clinical features suggestive of Klinefelter's Syndrome. The constitution of the patient was verified by GTG-banding, QFQ-banding, Fluorescence in Situ Hybridization and Polymerase Chain Reaction. Accordingly, we report the finding of a structurally abnormal chromosome Y with no detectable DYZ3 centromeric sequence and with no detection of AZF a, AZF b and AZF c, with clinical features suggestive of Klinefelter's Syndrome. This is the first reported case of Klinefelter's Syndrome involving a neocentromic Y among previously described cases with a neocentromere. Case presentation we report on a 23 years old man with a de novo 47,XX,+mar.ish der(Y)neo(Y)(pter-->p11.2::q11.23-->neo-->q11.23-->qter)(DYZ3-,SRY+,WCPY+) chromosome complement, accompanying with azoospermia and some of other clinical features suggestive of Klinefelter's Syndrome. The constitution of the patient was verified by GTG-banding, QFQ-banding, Fluorescence in Situ Hybridization FISH and Polymerase Chain Reaction PCR. Conclusions It can be inferred that a neocentromic Y is formed by identification of FISH, PCR and the fact that this markerof Y chromosome is present in 100% of peripheral blood cells and has been efficiently retained through cell divisions despite the absence of the endogenous cen­tromere region. To our knowledge, this is the first reported case of Klinefelter's Syndrome involving a neocentromic Y among previously described cases with a neocentromere, which adds to the catalog of chromosomal aberrations. The present study not only improves the understanding of karyotype/phenotype relationships between neocentric marker Y chromosomes and KFS male infertility, but also supports the hypothesis that the combined application of molecular cytogenetic analysis might help to identify breakpoints, origins, and the constitution of the marker chromosomes.

SUN-029 Diabetes Mellitus Associated with Klinefelter Syndrome

Background: It has not been clarified why diabetes mellitus develops in patients with Klinefelter’s syndrome. However the association between both diseases is frequent. Clinical Case: A 31-years-old man with type 2 diabetes diagnosed 2 months ago who received metformin for treatment. He presented to the hospital with dysuria, polyuria, polydipsia, weight loss, hyporexia, vomiting and drowsiness. On examination: BP: 110/60 mmHg, HR: 108 lp, FR: 24 rp, T °: 37 ° C, BMI: 31.4 kg / m2, oral mucosa dry, bilateral gynecomastia, subcutaneous cellular tissue of gynecoid distribution. His body hair was thin. His penis was small and both testicles were prepubertal. Laboratory: Glucose: 410 mg / dl; HbA1c 15.2%; creatinine: 1.01 mg / dl; arterial gases: pH 7.14 pCO2: 20, HCO3: 6.6, AG: 29. Normal electrolytes. Ketonuria: 3+. We concluded: diabetic ketoacidosis. In addition, FSH 61.18 μU / ml (RR: 1.5-12.5); LH: 28.47 μU / ml (RR: 0.7-8.6); Total testosterone: 0.41 ng / ml (RR: 2.8-8), compatible with hypergonadotropic hypogonadism. Therefore a karyotype is requested in peripheral blood, resulting in 47, XXY in 20 metaphases analyzed. Klinefelter’s syndrome was diagnosed from his physical characteristics, hormonal findings and his chromosomal aberration. He received testosterone undecanoate every 4 weeks, NPH insulin 12 IU / 8UI plus metformin 850 mg every 12 hours. Three months later: baseline glucose 89 mg / dl and HbA1C of 9.5%. Conclusion: We present the case of a young male with diabetic ketoacidosis and hypogonadism, secondary to Klinefelter syndrome. Klinefelter syndrome is associated with Diabetes mellitus with a RR that varies from 1.64 to 7.06 according to current literature. In addition, we highlight the importance of the medical history and physical examination for an adequate diagnosis of rare conditions such as Klinefelter Syndrome. Reference: 1. Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. Septembere 2018;86:135-44.

SUN-161 Primary Aldosteronism and Klinefelter’s Syndrome: Two Cases

Background: Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of LH receptor in patients with PA has been reported, however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Clinical Cases: Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a two-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Conclusion: Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered.