Katie and her husband, Simon, had never heard of XXY, and their midwife wasn’t very helpful either. XXY, also known as Klinefelter syndrome, is a genetic condition that can cause infertility and other health problems; it occurs when a child, usually assigned to a man at birth, is born with an extra X chromosome in addition to the usual X and Y.
Sex chromosome variations, in which people have excess or lack X or Y, are the most common chromosome disorders, occurring in as many as one in 400 births. Yet the majority of affected people don’t even know they have them. That’s because these conditions can fly under the radar; they are not life-threatening or necessarily even life-limiting and do not often have telltale features that raise red flags. Still, the diagnosis can cause distress.
As more expectant parents opt for non-invasive prenatal testing in hopes of ruling out serious conditions, many of them are surprised to find that their fetus has a much less serious — but much less well-known — condition. Because so many variations of sex chromosomes have gone undiagnosed historically, many ob-gyns are unfamiliar with these conditions, forcing families to navigate the unexpected news on their own. Many end up seeking information from advocacy groups, genetic counselors, and even Instagram as they devise their next steps.
The information landscape has changed dramatically since the advent of non-invasive prenatal screening (NIPS) ten years ago. The increasingly popular first-trimester blood tests that debuted in 2011 to detect Down syndrome have added a broader spectrum of conditions to their panel over time, including sex chromosome aneuploidies — the medical name for an atypical number of chromosomes.
“The scariest thing is that this diagnosis is based on a test that we didn’t really understand.”
In 2020, the American College of Obstetricians and Gynecologists approved NIPS at any age, making the blood test a routine part of pregnancy care. Parents usually use these tests to rule out Down syndrome or more serious conditions, in many cases to find out something they didn’t even know their baby was being screened for. “The scariest part is that this diagnosis is based on a test that we didn’t really understand,” Simon says. Katie adds, “We assumed the test would only detect very serious things.”
To add to the complexity, NIPS is not as reliable for sex chromosome aneuploidies as it is for Down syndrome, underscoring the importance of confirming a positive screening result during pregnancy via amniocentesis or chorionic villus sampling (which examines placental tissue), or with a blood test. sample after the baby is born. Still, data suggests that “some women have chosen to terminate pregnancies solely on the basis of: [noninvasive prenatal screening] results, potentially causing unaffected fetuses to abort,” says a 2016 article in Prenatal Diagnosis.
About 40% of men with XXY are diagnosed over the course of their lives, usually when they experience fertility problems as adults, says Nicole Tartaglia, a global expert on sex chromosome variations. People with XXY may have learning disabilities and challenges with social interaction, along with physical traits such as small testicles, a less muscular body, and less facial and body hair. But most people with Klinefelter syndrome grow up to lead productive, healthy lives.
Meanwhile, only 10% of people with XXX or XYY are aware of their condition. But these numbers are growing as genetic testing becomes more widespread. “Judging by the number of phone calls we get, the proportion of those who go undiagnosed is getting smaller,” she says.
