Table 1.

Comorbidity of Klinefelter syndrome (KS)

	Findings	References
Cancer
Extragonadal germ cell tumors	Nonseminomatous subtype	Nichols (1987)103
	Younger than non‐KS
Breast cancer	4‐ to 60‐fold compared with non‐KS	Swerdlow et al (2005)94 Brinton (2011)75 Sasco et al (1993)74 Gomez‐Raposo et al (2010)76
	Younger than non‐KS
Metabolism
Obesity, metabolic syndrome	Abdominal fat is increased	Bojesen et al (2006)90 Aksglaede (2008)104 Laaksonen (2014)105 Pasquali et al (2013)38
	4‐ to 5‐fold compared with non‐KS
	Odds ratio of 2.3 with low testosterone
	Effect of TRT on BMI is controversial
Diabetes	8%‐50% in Western countries	Takeuchi (1999)106 Lichiardopol (2004)107 Swerdlow et al (2005)94 Bojesen et al (2006)90 Pasquali et al (2013)38
	3.9%‐4.1% in Japan
	HR of 2.21 for T1D and 3.71 for T2D
	Prediabetes is more frequent
	No effect of TRT
Cardiovascular disease
Congenital abnormalities	Mitral valve prolapse	Fricke (1981, 1984)108, 109 Pasquali et al (2013)38
	Diastolic dysfunction
Conduction defects	Short QTc interval	Jorgensen (2015)93 Liu (2010)110 Lai (2009)111
	Atrial fibrillation
Thrombosis	Hazard ratio of 3.6 to 5.7 for pulmonary thrombosis	Bojesen et al (2006)90 Swerdlow et al (2005)94 Campbell et al (1981)96
	Hazard ratio of 6.6 to 7.9 for deep vein thrombosis
Bone disease
Osteoporosis/fracture	Decreased bone mineral density	Bojesen et al (2006)90 Swerdlow et al (2005)94 Bojesen and Gravholt (2011)68 Ferlin et al (2015)98
	Femur fracture
	8‐fold increase compared with non‐KS
	Low levels of 25‐OH vitamin D
Immunological diseases
Autoimmune diseases	13‐fold increase in systemic lupus erythematosus compared with non‐KS	Scofield (2008)112 El‐Mansoury (2005)113 Sawalha et al (2009)100 Rovensky et al (2010)101 Seminog et al (2015)102
	Rheumatic diseases
	Addison's disease
	Diabetes mellitus type 1
	Multiple sclerosis
	Acquired hypothyroidism
	Sjogren's syndrome

TRT, testosterone replacement therapy.