(See also Overview of Chromosomal Anomalies Overview of Chromosomal Anomalies Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more .)
Klinefelter syndrome is the most common sex chromosome disorder Overview of Sex Chromosome Anomalies Sex chromosome anomalies may involve aneuploidy, partial deletions or duplications of sex chromosomes, or mosaicism. (See also Overview of Chromosomal Anomalies.) Sex chromosome anomalies are... read more , occurring in about 1/500 live male births. The extra X chromosomes are maternally derived in 60% of cases. Germ cells do not survive in the testes, leading to decreased sperm and androgens.
Affected boys tend to be tall with disproportionately long arms and legs. They often have small, firm testes, and about 30% develop gynecomastia Gynecomastia This photo shows enlarged breast tissue in a male patient. Gynecomastia is hypertrophy of breast glandular tissue in males. It must be differentiated from pseudogynecomastia, which is increased... read more .
Puberty usually occurs at the normal age, but often facial hair growth is light. There is a predisposition for verbal learning disorders. Clinical variation is great, and many 47,XXY males have normal appearance and intellect. Testicular development varies from hyalinized nonfunctional tubules to some production of spermatozoa; urinary excretion of follicle-stimulating hormone is frequently increased.
Mosaicism occurs in about 15% of cases. Males with a normal male karyotype (XY) in some cells may be fertile and have less obvious malformations. Some affected men have 3, 4, and even 5 X chromosomes along with the Y. As the number of X chromosomes increases, the severity of intellectual disability and of malformations also increases. Each extra X is associated with a 15- to 16-point reduction in IQ, with language most affected, particularly expressive language skills.
Diagnosis of Klinefelter Syndrome
Prenatal diagnosis often when cytogenetic testing is done for other reasons such as advanced maternal age
Detected postnatally on clinical appearance
Cytogenetic testing by karyotyping, fluorescent in situ hybridization (FISH) analysis, and/or chromosomal microarray analysis
The diagnosis of Klinefelter syndrome is suspected on physical examination of an adolescent with small testes and gynecomastia. Many men are diagnosed during an infertility evaluation (probably the majority of nonmosaic 47,XXY males are subfertile).
Diagnosis is confirmed by cytogenetic analysis (karyotyping, FISH analysis, and/or chromosomal microarray analysis). (See also diagnosis of chromosomal anomalies Diagnosis Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more and Next-generation sequencing technologies Genetic Diagnostic Technologies Genetic diagnostic technology is rapidly improving. A small amount of DNA can be amplified using the polymerase chain reaction (PCR) process, which can produce millions of copies of a gene or... read more .)
Treatment of Klinefelter Syndrome
Fertility preservation counseling just after onset of puberty
Males with Klinefelter syndrome should be evaluated by an endocrinologist to determine whether testosterone supplementation is indicated. Testosterone therapy is typically started at puberty to ensure the development of male sexual characteristics, muscle bulk, bone structure, and better psychosocial functioning. More recent studies have suggested that early hormone therapy may help with developmental and behavioral problems in boys with 47,XXY.
Boys with Klinefelter syndrome usually benefit from speech and language therapy and neuropsychologic testing for language comprehension, reading, and cognitive deficits.
After the onset of puberty, boys should receive counseling regarding fertility preservation.