Klinefelter syndrome (KS) is the most frequent sex chromosome disorder in males, but the phenotype varies greatly and is therefore highly under-diagnosed. We aimed at describing the phenotypic characteristics throughout life from clinical follow-up of our large cohort of patients with KS.
A retrospective observational study of 166 males with nonmosaic 47,XXY KS aged 0.3-80.3 years. Data on phenotype, growth, body composition, bone mineral density, sex hormones, lipids, glycosylated haemoglobin (HbA1C) and prostate-specific antigen were recorded. In addition, histological examination of testicular biopsies from 29 patients was performed.
Patients with Klinefelter were taller already in childhood. All patients had smaller testicular volume and elevated luteinizing hormone (LH) and follicle-stimulating hormone levels in adulthood. Cryptorchidism was reported in 14%, gynaecomastia in 44%, and 36% required speech therapy or educational support. The abnormal biochemical parameters became evident after onset of puberty and correlated with histological findings of a gradual deterioration of seminiferous tubules and massive Leydig cell hyperplasia in adults.
Our patients presented with a wide spectrum of the classical Klinefelter symptoms. In adulthood, two features were consistently present in every patient: small testes and high LH/testosterone ratio, often despite normal testosterone levels. Such biochemical parameters combined with small testes should lead to a suspicion of KS.