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Research
Not the end of the road: Delivering the diagnosis of sex-chromosome trisomy
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Even if you've never heard the word "trisomy," you probably know someone with the condition. March is Trisomy Awareness Month, a time to raise awareness about trisomy conditions and the challenges they can pose to individuals and families.
Trisomy means having three copies of a chromosome instead of two. Down syndrome, or trisomy 21, is the best-known trisomy. Certain less-known types occur for other chromosomes, including the sex chromosomes. The traits, or phenotypes, associated with sex-chromosome trisomy vary widely among individuals—which poses significant challenges for discussions between health care providers and families. Research supported by Mayo Clinic's Center for Individualized Medicine (CIM) highlights how providers might better deliver the diagnosis of sex chromosome trisomy.
"It's much easier to give prospective parents a clear vision of what life would be like for a child with Down syndrome because it's well documented, and the perspective is very positive," says Megan A. Allyse, Ph.D., a researcher in the CIM Bioethics Program who co-authored the study. "Whereas we can't necessarily give a clear picture for a child with sex chromosome trisomy. The child may be indistinguishable from most other children, or may struggle with social and educational factors. The uncertainty is frustrating for both parents and counselors."
Trisomy is usually caused by a genetic mutation. Most people have either XY or XX sex chromosomes. Individuals with sex-chromosome trisomy can have XXX (known as trisomy X), XXY (Klinefelter syndrome) or XYY (Jacob's syndrome). Often sex chromosome trisomy isn't diagnosed until adolescence or even adulthood. Increasingly, however, the diagnosis is made before birth, as parents opt for early prenatal screening to determine whether they're having a boy or girl. The new genetic testing that provides that answer can also detect evidence of extra X or Y chromosomes.
"The parents aren't thinking about screening for an X- or Y-chromosome trisomy," Dr. Allyse says. "But genetic testing can indicate a high risk of sex chromosome trisomy, which additional diagnostic tests might confirm. Most parents going into this process of prenatal genetic screening aren't expecting that outcome. We find that their minds generally go to the worst possible scenario."
That anxiety might be fueled by misinformation. Studies conducted decades ago of individuals in institutional settings found many examples of sex chromosome anomalies. "Conclusions were made that if your child has a diagnosis of XYY, he's more likely to become a criminal. But broader population studies have found that this is absolutely not true," says Kirsten Riggan, a research coordinator in Mayo Clinic's Biomedical Ethics Research Program who also co-authored the CIM study.
Parents and individuals surveyed for the CIM study expressed almost unanimous interest in more optimistic portrayals of their condition from their providers, even when the outlook is uncertain. The study participants—who were recruited nationwide with help from the Association for X and Y Variations (AXYS), a patient-advocacy group—also noted a need for greater coordination of their children's medical care and direction in accessing follow-up care and support.
"What families want to hear is that this diagnosis is something we know about, other people have had this experience, and we can help you get through this," Dr. Allyse says. "Lots of children live with this condition. It may mean some adjustments. But it's not by any stretch of the imagination the end of the road."
Wide variation in traits
It's difficult to generalize about the traits of sex chromosome trisomy. Many individuals have mild symptoms, but some have significant health problems needing specialty care.
Females with trisomy X tend to be tall but often have no physically distinguishable characteristics. Symptoms may be mild, usually involving minor motor development and language delays. Sex development and fertility are frequently normal. "Typically, the phenotype isn't as noticeable with trisomy X," Ms. Riggan says.
Similarly, individuals with XXY or XYY may be taller than average. They may have a predisposition for weight gain that can lead to diabetes, and experience delays in development and learning. But not all do.
"There are plenty of men who grow up, graduate from college, get married and find out they have Klinefelter syndrome only when they try to have children," Dr. Allyse says. Men with Klinefelter syndrome generally have impaired fertility, although Mayo Clinic has experience helping men with the condition to father children through in vitro fertilization. Men with Jacob's syndrome generally have normal sexual development and fertility.
The biggest challenge is a correlation in males between sex chromosome trisomy and impaired executive function, or the thinking processes that control behavior. "Sometimes these boys have a misdiagnosis of attention deficit/hyperactivity disorder, antisocial behavior or autism," Dr. Allyse says. "The finding of a genetic trisomy—which we often see when boys are ages 10 to 15—comes as a huge relief to the family because they finally have an underlying cause for the behavior, and can get support.
"We need more education among non-genetic health providers about the phenotypic signs of sex chromosome trisomy, so children can be diagnosed earlier," she adds. "What we hear from these families is, 'I just wish somebody had told us when we got the diagnosis that it was possible for us to have a great life.' "
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