Growth hormone deficiency

Because the chain of events involved in growth hormone deficiency is so complex, researchers at Boston Children's Hospital are investigating the different events that can cause a child to have short stature. Not all of these individual defects are well understood or easy to detect with a test, making this research vital to treatment strategies.

In search of height-regulating genes

It's long been obvious that height is an inherited trait, but so many genes probably contribute to stature that no one's been able to pinpoint a single one. But a collaboration co-directed by Joel Hirschhorn, MD, PhD, of Children's and the Broad Institute has done just that.

In the most thorough search ever done for genes that regulate height, Hirschhorn and his research colleagues scanned the complete genomes of nearly 5,000 people—some 30,000 genes each. They then validated their findings in samples from more than 22,000 adults and nearly 7,000 children. Many genes they'd expected to be players didn't show any special association with height. But one gene, called HMGA2, did: Having a "C" rather than a "T" at a certain spot on the gene added a small gain in height.

Hirschhorn speculates that HMGA2 may have something to do with early cell proliferation, possibly in the pituitary gland, which makes growth hormone. Interestingly, increased HMGA2 activity is also associated with certain types of cancer, perhaps triggering a similar but unwanted cell proliferation.

Although this HMGA2 variant explains less than half a percent of a population's height variation, its discovery is the first clue that researchers may be able to find many other genes that regulate height and learn how they work together.

Knowing the responsible genes will give insights into the biology of growth, which is poorly understood. And in the clinic, genetic testing might help reassure parents that their child's short stature is simply an inherited trait, not part of a nutritional problem or underlying disease.

Height and children with cancer

Because childhood cancer survivors may experience growth hormone deficiency or have other conditions that effect growth, Children's is studying this unique patient population’s needs by assessing the effects of cancer and its treatment on the endocrine system. The good news is that multiple studies have shown that growth hormone is not associated with cancer recurrence, so most cancer-related growth hormone deficiency can be treated.

Laurie Cohen, MD, works with many cancer survivors who struggle with growth hormone deficiency and has had scores of gratifying success stories. (In fact, she estimates that 60 to 70 percent of her patients are cancer survivors.)

“I can tell after a couple months of treatment whether a kid is profoundly growth hormone deficient, and it’s pretty obvious in my cancer survivors too,” says Cohen. “The first time they come back after having started growth hormone treatment, and they’ve grown like a weed and totally thinned out, it’s extremely gratifying.”