Oftentimes children are cautioned against growing up too quickly; however, researchers may have uncovered a genetic cause for the small subset of boys and girls who physically undergo puberty at uncharacteristically young ages.
Precocious puberty, which is defined by the development of secondary sexual characteristics before 8 years in girls and 9 years in boys, has been associated with an increase in conduct and behavioral disorders during adolescence. The disorder affects more girls than boys, and is becoming more common, although the reasons for this are unclear.
Recently, the media has questioned whether puberty is starting earlier, even in those children without this condition. And a 2011 study by the American Academy of Pediatrics (AAP) followed American girls of various ethnicities, locations and backgrounds, and demonstrated that by 7 years old, more than 10 percent of Caucasian girls and 23 percent of African-American girls showed signs of breast development, indicating that puberty has begun.
“Since young children are not emotionally ready for these adult changes in their bodies, precocious puberty can cause a great deal of anxiety related to the feeling of being different, as well as to the physical development itself,” says the study’s co-author Andrew Dauber, MD, MMSc, instructor in pediatrics at Boston Children’s Hospital. “In terms of physical development, precocious puberty can result in shorter stature in adults because the bones stop growing prematurely. Among girls, early development can increase the risk of breast cancer.”
Much research has assessed whether early puberty was genetic, or passed down from one generation to the next, but far less research has been conducted to find specific genetic causes of precocious puberty.
To better understand this condition, Ana Claudia Latronico, MD, PhD, of the University of Sao Paulo, Ursula Kaiser, MD, of the Brigham and Women’s Hospital, along with Dauber have been collecting genetic information from families that have early puberty.
For this study, the researchers analyzed 40 individuals from 15 families with precocious puberty through whole exome sequencing, which analyzes the protein-coding component of the genes, to identify the mutation. “With this large sampling of multi-generations of family members, we thought we could find some of the causes of precocious puberty,” Dauber says.
In five of the 15 families, the researchers identified four mutations in the MKRN3 gene. The MKRN3 gene is responsible for coding a protein called makorin ring finger protein 3, which is thought to help tag other proteins for degradation. The genetic mutations resulted in truncated MKRN3 proteins and disruption of MKRN3 protein function.
The study appeared online June 5, in The New England Journal of Medicine. The results will also be presented at The Endocrine Society’s 95th Annual Meeting & Expo in San Francisco on June 17.
“Our research is going to open the door for an entirely new understanding of what controls the timing of puberty.”
Importantly, the researchers also discovered that symptoms of central precocious puberty only manifest themselves when the father is the carrier of the mutated gene.
“Our research is going to open the door for an entirely new understanding of what controls the timing of puberty,” Dauber says. “It also will allow doctors to diagnose the cause of precocious puberty in a subset of patients.”
Boston Children’s Hospital, the National Institutes of Health and research funding agencies in Brazil supported the study.