Klinefelter syndrome
Incidence
1.18 per 1000 live births, A recurrence risk of 1% or less, with family studies needed only for unusual X or Y chromosome rearrangements.
Clinical Characteristics
Subtle pattern of manifestations including tall stature, asthenic habitus, small testes, gynecomastia, sexual immaturity. Klinefelter syndrome "variants" include disorders with more severe clinical features and additional X or Y chromosomes as in the karyotypes 48,XXXY, 48,XXYY, and 49,XXXXY. More than 10% of males presenting with sterility and 3% of those with breast cancer will have Klinefelter syndrome. The additional X interferes with male hormone (testosterone)-secreting cells in the testis, but the exact mechanism is unknown. The immature body habitus, feminine features (like gynecomastia, high voice, or sparse hair), and sterility reflect testosterone deficiency. Only 18% of individuals with 47,XXY Klinefelter syndrome will have major congenital anomalies, and most are recognized after puberty. The karyotype is diagnostic, and serum testosterone levels should be considered in postpubertal patients. Individuals with Klinefelter syndrome should have normal life expectancy except for a six-fold increased risk of cerebrovascular disease (strokes) and a 1.6% lifetime incidence of cancer. Delayed speech is found in 51%, motor delays in 27%, and school maladjustment in 44%. Early onset of puberty has been reported in association with a germ cell tumor. Antisocial behaviors including theft or arson, alcoholism, and aggressiveness are described in some reports; others describe XXY men as having similar employment and social status to their peers. Psychiatric disorders such as manic-depressive illness, psychosis, depression, and anorexia nervosa may be increased. Other medical complications include eye anomalies such as coloboma, strabismus or choroidal atrophy, cleft palate, heart defects like aortic stenosis or mitral valve prolapse, inguinal hernia, and genital anomalies such as cryptorchidism (undescended testes), hypospadias, or small penis. Hearing deficits may occur, although most studies do not document higher numbers of respiratory infections during childhood. Increased frequency of autoimmune diseases such as collagen vascular disease or diabetes mellitus has been reported. Unusual complications include distal muscle weakness and severe varicose veins have been reported.
Precipitants
none
Provocation Tests
none
Diagnostic Procedures
80% have karyotypes of 47,XXY, 10% of 46,XY/47,XXY, and the remainder multiple X or Y chromosomes.