Although considered the most common chromosomal disorder in humans, the subtle symptoms of Klinefelter syndrome can result in a man living with the condition his entire life without ever being diagnosed.
Klinefelter affects only males. Instead of having the usual XY chromosome pattern of most males, boys are born with an extra X chromosome in most of their cells, causing an XXY pattern. The exact cause of the extra X chromosome is unknown, but an estimated one in 500 males has the extra X, which can come from either parent. The syndrome, however, is a random occurrence and is not inherited.
Also called the XXY condition or 47, XXY, Klinefelter syndrome gets its name from physician Harry Klinefelter, who published a paper in 1942 about several men with enlarged breasts and small testes and an inability to produce sperm. Whether a man will have these traits or others, such as sparse facial and body hair or poor motor skills and weak muscle tone, depends on the number of XXY cells he has and the amount of testosterone he produces. Many men, however, don’t have noticeable symptoms.
“The traits are not recognizable unless they are severe,” said Ilene Fennoy, M.D., a clinical professor of pediatrics at Columbia University Medical Center in New York, who specializes in treating boys with the disorder.
“About 66 percent of males with Klinefelter syndrome are never diagnosed, and only about 10 percent are diagnosed prior to puberty,” she said. The majority of cases detected before a boy reaches puberty are detected during prenatal amniocentesis, according to Fennoy.
Many other cases are diagnosed when men undergo fertility testing. Although XXY males can have normal sex lives, between 95 and 99 percent are infertile because they produce no or minimal sperm. Klinefelter is a leading cause of male infertility.
Young boys with the disorder, however, are likely to have language, social, or physical development problems. Symptoms include delayed speech, ADHD, motor delays, sensitivities to sounds or touch, and learning disabilities.
Symptoms like these led to the diagnosis of Roberta Rappaport’s son at age 12. His pediatrician ﬁrst noticed early language delays and suggested speech therapy. His nursery school teacher was next to point out that the child was “not settling down like he should by his age.”
“We kept telling our pediatrician about comments we’d get from teachers or things we noticed. Finally at our son’s 12-year check-up, his doctor linked the symptoms together and sent us for genetic testing,” recalled Rappaport, who with her husband founded the Chicagobased American Association of Klinefelter Syndrome Information & Support.
Pediatricians, endocrinologists, geneticists, speech therapists, psychologists, and other medical experts may be involved in assessing a boy for the condition.
Fennoy said she prefers to treat young patients with “psychiatric therapy and behavioral counseling rather than medical interventions.” Some physicians, however, suggest starting testosterone replacement at the onset of puberty to allow a boy to undergo the physical changes that usually occur at puberty, such as increasing muscle mass, developing a deeper voice, and growing facial and body hair.
Researchers are currently studying the efﬁcacy of testosterone replacement therapy in the pediatric population. A clinical trial at the University of Colorado at Denver is currently enrolling 50 XXY adolescent males, ages 8–18, to determine whether testosterone replacement therapy leads to changes in psychological factors and motor skills. The study will be completed in February 2017.
Another trial at Denmark’s Aarhus University will conclude in July 2014. It is investigating the quality of life in adult males with Klinefelter. Participants are being surveyed on their marital status, fatherhood, education, and mental and physical health.
Rappaport says her son, now 44, is a talented handyman, but has poor organizational skills. “Klinefelter is a spectrum disorder, meaning it goes in a bell curve,” she said. “I also know many men who function well as doctors and lawyers, so it’s not insurmountable.”