The tetrasomy X (49,XXXXY) syndrome is a rare X-chromosome polysomy with an estimated incidence of 1 in 85,000 male births [1]. The chromosomal constitution and clinical findings were described by Fraccaro et al. in 1960 [2]. Tetrasomy X has been considered as the most severe variant of Klinefelter’s syndrome which is a common sex chromosomal abnormality caused by the presence of one additional X chromosome in males and has a prevalence of 1 in 500 [1-4]. The most common sex chromosome aberrations in live births are 47,XXY, 47,XXX, and 47,XYY [5]. However, rare syndrome variants with X and Y polysomy, mosaicisms and aberrant chromosomes have been reported, including 48,XXXY, 48,XXYY, 49XXXXY, 47,XXY/ 48,XXXY and 48,XXXY/49,XXXXY [6,7]. The clinical features of Klinefelter’ syndrome are variable but often include infertility, gynecomastia, eunuchoidism, small testes and penis and hypergonadotropic hypogonadism. The extra X chromosome in these patients accounts for the clinical phenotype, but this ranges from mild (only infertility) to more severe with physical anomalies and mental retardation. The classical features of 49,XXXXY syndrome are growth and mental retardation, severe speech impairment, multiple skeletal defects, and dental, craniofacial and genital abnormalities. These patients have also phenotypic similarities such as strabismus, microcephaly, epicanthal folds, hypertelorism, cleft palate and heart disease [2,8,9]. We studied a patient with the 49,XXXXY karyotype, verified and identified by quantitative fluorescent polymerase chain reaction (QF-PCR) amplification of seven short tandem repeat (STR) markers located on X and Y chromosomes, and two additional regions (AMXY for X and Y, and SRY for Y chromosomes).