Genetic Cause of Gigantism Explored

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Genetic Cause of Gigantism Explored
Genetic Cause of Gigantism Explored

Duplication of a gene on the X chromosome may be responsible for excessive growth in children, according to new research published in the New England Journal of Medicine.

“Finding the gene responsible for childhood overgrowth would be very helpful, but the much wider question is what regulates growth,” Constantine Stratakis, MD, DSc, lead author and scientific director of the Division of Intramural Research at the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), said in a press release.

“As pediatricians and endocrinologists, we look at growth as one of the hallmarks of childhood. Understanding how children grow is extraordinarily important, as an indicator of their general health and their future well-being.”

Genetic causes of gigantism and acromegaly, however, are not well defined. To learn more, Dr. Stratakis and colleagues conducted clinical and genetic studies, including whole-genome analysis, of samples from 43 patients with gigantism. They then sequenced the implicated gene in 248 samples from patients with acromegaly.

Results revealed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism, four of which were obtained from members of two unrelated kindreds and nine of which were from patients with sporadic cases of the condition.

All patients experienced disease onset during early childhood, according to the data.

In contrast, patients with gigantism who did not have microduplication on Xq26.3 did not present with the disease before age 5 years.

Genomic evaluation of the Xq26.3 region indicated that the microduplications contain four protein-coding genes. The researchers found overexpression of only one gene — GPR101 — in the pituitary lesions of patients.

Additionally, in 11 of 248 patients with acromegaly, a recurrent GPR101 mutation was identified, mostly in tumors, the researchers wrote, and transfection of the mutation into rat GH3 cells induced increased production of growth hormone (GH) and GH-producing cells.

“We believe GPR101 is a major regulator of growth,” Dr. Stratakis said. 

The next step identifying how the protein derived from GPR101 operates, Dr. Stratakis said, and hopefully developing treatments for gigantism as well as advancing researchers' understanding of undergrowth, according to release.


  1. Trivellin G et al. N Engl J Med. 2014;doi:10.1056/NEJMoa1408028.
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