The 49,XXXXY syndrome has not been reported to be associated with maternal age or a hereditary disease [4]. The extra X chromosomes result sporadically from either meiotic non disjunction where a chromosome fails to separate during the first or second division of gametogenesis or from mitotic non disjunction in the developing zygote. The likelihood of X chromosome non disjunction increases with advancing maternal age. It is believed the that 49,XXXXY syndrome occurs during maternal non disjunction both in meiosis I and II [15,16]. In our patient, all the X chromosome-specific STR markers we tested for were inherited from his mother and heterozygosity was retained in all regions (proximal, medial and distal regions) of all. These are the expected conditions of non disjunction in both meiosis I and meiosis II. Molecular genetic analyses using polymorphic DNA markers have enabled the study of non disjunction of fetal aneuploidy and the determination of parental origin and cell stage errors at meiosis I or II [11,13-15].

The common presentations of the 49,XXXXY syndrome during early infancy have included variable combinations of craniofacial dysmorphism, abnormal genitals and delayed developmental milestones that lead to chromosome karyotyping [4,9,18-20]. Our patient had classical facial features of the 49,XXXXY syndrome. Whereas coarsening of facial features has been reported to occur later in life [19], these were evident very early in our patient. Also newborns with the 49,XXXXY syndrome were reported to have below average lengths and weights at birth, and demonstrated significant catch-up growth in later gestation [4,20]. In our patient, the growth parameters were appropriate for his gestational age, but he failed to thrive thereafter. Multiple skeletal anomalies, with radioulnar synostosis in particular, present in our patient, are characteristic of the 49,XXXXY syndrome [4,18]. The addition of more X chromosomes in polysomy X males results not only in infertility, but also in hypoplastic and undervirilized genitalia [18]. The majority of patients with 48,XXXY and 49,XXXXY syndromes have been reported to have small testes (94%), small penis and hypoplastic scrotum (80%) cryptochidism (30%) and ambiguous genitalia [21]. Mental retardation is anticipated to be a major problem in this patient. A direct relationship between the number of supernumerary X chromosomes with phenotypic abnormalities and mental retardation has been reported, the severity of mental retardation increasing with each additional X chromosome [18,21]. Patients with 49,XXXXY syndrome have varying degrees of mental retardation [22]. Our patient has developmental delay and showed speech and articulation problems. These findings are in agreement with the important delay in language development and reading difficulties before adolescence that has been seen in patients with sex-chromosomal abnormalities [23,24].

We conclude that the 49,XXXXY syndrome is different from the Klinefelter’s syndrome in many ways. Chromosome karyotyping is warranted in the presence of facial dysmorphism or other somatic abnormalities, to exclude underlying sex chromosomal aneuploidy disorders such as the 49,XXXXY syndrome. Evaluation of exceptional instances of segregation failure may be useful in improving our understanding of the general mechanisms of non disjunction. Molecular techniques could be useful for the pre- and post-natal diagnosis of the common aneuploidies and for determining their parental origin. This kind of study will improve knowledge about the mechanisms of the development of aneuploidies, and provide an opportunity to study the effect of the 49,XXXXY syndrome on the phenotype, and enable appropriate and rapid genetic counseling.