Growing Up Too Fast: Precocious Puberty's Gene Link

The case offers the first evidence of a genetic culprit for the problem.


Feb. 14, 2008— -- Think back to the drastic changes with which your body was assaulted when you hit puberty. Now, try to imagine the same set of changes happening when you were 8 years old.

Such is the plight of children who experience precocious puberty — a condition in which their bodies begin to mature years too early.

Now, for the first time, researchers have found a gene mutation that could be responsible for a small number of these cases.

"This is the first known genetic cause of precocious puberty," says lead study author Dr. Ursula Kaiser, chief of the division of endocrinology, diabetes and hypertension at Brigham and Women's Hospital in Boston, Ma. "It points additionally to the role of genetics in the timing of puberty."

The finding will be published in the upcoming issue of the New England Journal of Medicine.

Kaiser says that the gene in question was first identified a few years ago as having a role in reproductive health. In these cases, however, a flawed version of the gene was found not in those who underwent early puberty, but instead in patients who failed to go through puberty altogether.

To learn more, Kaiser collaborated with a research group in Brazil, comparing the DNA of about 53 girls who had gone through early puberty to 150 normal female subjects who had not gone through early puberty.

The mutant gene was only found in one 8-year-old girl who had gone through early puberty — and none of the normal women. The researchers believe the mutant gene led to an early surge of the sex hormone estrogen, which subsequently set the chain of events associated with puberty into motion.

Kaiser says this suggests that the gene may well act as a genetic "switch" for puberty — though she and endocrinologists not involved with the research agree that the mutation itself is not a common cause of the condition.

"This particular gene, at least, does not appear to be a common cause of precocious puberty," says Dr. Mark Groshek of the departments of pediatrics with Kaiser Permanente Colorado. "It opens a door, though, to suggest it may be possible to find other genes that explain precocious puberty in other children.

"Identifying a genetic link to any form of precocious puberty is useful, because it demonstrates that in at least some cases, there is a genetic cause."

Doctors generally define precocious puberty as the development of secondary sex characteristics — such as the growth of pubic hair, development of breasts in girls and lowering of voice in boys — before age 8 for girls and age 9 for boys.

The condition is not common, and for reasons still not entirely understood it occurs more often in girls than in boys.

And in most cases, the underlying causes of precocious puberty remain a mystery, though certain hormone disorders and brain tumors have been known to bring the condition about.

Fortunately, the condition is treatable. Treatment usually involves once-a-month injections to halt the puberty process until the child is older. Halting the treatments allows puberty to continue as normal.

But the psychological toll of the condition can be significant, and its young sufferers often require counseling to cope with the effects of being more sexually developed than their friends.

Some endocrinologists fear that recent research shows a steady decrease in the age that children — specifically girls — are hitting puberty.

According to research first published in the journal Pediatrics in April 1997, the average age at which girls hit puberty may be falling. Researchers found that the average age for breast development or the growth of pubic hair was 9.7 years old for Caucasian girls and 8.1 years old for African-American girls.

A number of theories have emerged in an attempt to explain the trend. Dr. Robert Lustig, professor of pediatric endocrinology at the University of California at San Francisco, says that when it comes to the vast majority of these cases that are not genetic in origin, the chain of events that leads to early puberty is usually initiated between the ages of 6 and 8.

"In these cases, estrogens and other organic pollutants in the environment may be a more important issue [than gene mutations]," Lustig says. But, he adds, "obesity seems to be the most significant contributor to the 'epidemic' of precocious puberty, as [fat] tissue produces estrogen, which then causes breast development."

But other explanations abound. In a study released last November, for example, researchers at the University of Arizona found evidence that a stressful family environment may cause puberty to kick in early for young girls.

Still, if one thing remains clear, it is that any increase in the trend likely has little to do with genetic mutations.

"If precocious puberty has been increasing in frequency over the last few decades, it cannot be based on genetic changes," says Dr. Neil H. White, professor of pediatrics and medicine at the Washington University in St. Louis School of Medicine. "Changes in disease frequency as a result of genetics requires a long time and does not occur over a couple of decades."

Since the genetic mutation uncovered by Kaiser and her colleagues is so rare, a diagnostic test to detect the gene mutation would probably be of little use to parents who wanted to assess their children's risk of early puberty.

"For this to be useful in preventing cases of precocious puberty, this gene would have to be a common enough cause of precocious puberty to justify screening all children for this gene," Groshek says. "Whether this gene is unique to this girl or is found in others is not clear. It certainly is not common, based on this team's findings. So I don't see it having any potential at this time to help us find kids who are prone to precocious puberty."

Still, the finding may be useful on the therapeutic level, Kaiser says. Specifically, if doctors could find a way to manipulate this genetic switch, they may be able to exploit it to treat patients who suffer from early puberty or other reproductive problems — including infertility.

"We may eventually be able to tinker with the switch to induce fertility, or turn it off if you wish to switch off this pathway," she says.

And she says the research suggests the possibility that there are more such mutated genes out there that could lead to the condition.

"Probably this is really the tip of the iceberg," Kaiser says. "The genes involved in the timing of puberty are just now being uncovered.

"So while we're not so sure that this mutation is necessarily so common, it is a prototype for the genetic contributors to early puberty."