Mosaic tetrasomy 9p case with the phenotype mimicking Klinefelter syndrome and hyporesponse of gonadotropin-stimulated testosterone production.

Tetrasomy 9p is a rare clinical syndrome and about 30% of known cases exhibit chromosome mosaicism. The cases with tetrasomy 9p mosaicism have been reported to show the various phenotypes. On the other hand, Klinefelter syndrome is well recognized chromosomal abnormality caused by an additional X chromosome in males (47,XXY), and the characteristic clinical findings include tall stature, immaturity of external genitalia, testicular dysfunction. Here, we report a 10-year-old male with tetrasomy of 9p mosaicism, whose phenotypic feature is mimicking Klinefelter syndrome. He was referred to our hospital for inconspicuous penis. He showed tall height (+2.5 SD). Endocrinological examination revealed the poor testosterone response to human chorionic gonadotropin administration, which indicated the testicular hypofunction, whereas MRI revealed concealed penis as a cause of inconspicuous penis. Because of the phenotype mimicking Klinefelter syndrome, karyotype of his blood lymphocytes was analyzed, and an additional marker chromosome was detected in 6% of the investigated metaphases. Fluorescence in situ hybridization analysis revealed that the marker chromosome was an isochromosome 9p, which resulted in tetrasomy 9p. Chromosome analysis of buccal smear also showed mosaicism for two karyotypes: 5% of cells had the isochromosome of 9p, and the other cells showed normal. This case is the second case with tetrasomy 9p mosaicism mimicking Klinefelter syndrome phenotype in the world. Our case, together with previously reported cases with the same association, indicates the possibility of testicular hypofunction and urogenital anomalies induced by overexpression of some genes on chromosome 9p.