The incidence of 48,XXYY is estimated at between 1/18,000 and 1/ 50,000 [Muldal et al., 1962; Sorensen et al., 1978; Nielsen and Wohlert, 1990]. Approximately 2.3% of individuals with the clinical signs of Klinefelter’s syndrome have the 48,XXYY karyotype [Hasle et al., 1995]. Although frequently classified with 47,XXY due to shared characteristics such as hypogonadism, it has been recognized that 47,XXYY varies in medical, cognitive, and behavioral characteristics [Visootsak et al., 2007; Tartaglia et al., 2008]. It is generally associated with more pronounced phenotypic abnormalities, including mild craniofacial dysmorphism; skeletal anomalies such as radio-ulnar synostosis and clinodactyly; lower IQ, typically between 70 and 80; significant developmental delays; a higher risk of behavioral symptoms such as inattentiveness, hyperactivity, mood instability, and poor social function, and medical problems including neurological symptoms such as intention tremor; poor dentition, and reactive airway disease [Visootsak et al., 2007; Tartaglia et al., 2008]. Physical height is increased to a greater extent than in 47,XXY [Linden et al., 1995]. Individual case studies of clinical MRI findings in individuals with 48,XXYY have reported white matter hyperintensities in a
