"They don't meet the family's expectation of how a boy or girl should behave," said Family Acceptance Project Director Caitlin Ryan, a clinical social worker. "They see them as disobedient or disrespectful or willful. To punish a child or force them to wear clothes that feel wrong for them and make them feel humiliated damages their self-worth."
Ryan said there is a "dearth of information" for parents on how to deal with a child who is gender nonconformist.
While Nicole has been sure about her gender since she was a toddler, her parents faced enormous confusion, wondering if their son had a feminine side, was gay or, as it turns out, was a female trapped in a male body, according to the Globe.
Even their pediatrician wouldn't address the issue with them.
She excelled in middle school, serving as vice-president in the fifth grade, but one day a bully called her "faggot" and told his guardian that Nicole was using the boys' room. The school required her to use the staff bathroom, then assigned an adult to follow her daily routine so she wouldn't be further bullied. Jonas was teased as well.
The Maineses got the backing of the Maine Human Rights Commission, which agreed that Nicole had been discriminated against, according to the Globe. They joined the family in a lawsuit against the Orono School District, which is now pending.
The Boston legal organization Gay and Lesbian Advocates and Defenders (GLAD) is representing the family, which says the stigma got so bad after they took legal action that they had to move to a more diverse and open-minded town in southern Maine.
"It's the first time they've gone to school since this story has come out and the family is understandably cautious of the kinds of reactions they might get based on past experiences," GLAD spokeswoman Carisa Cunningham told ABCNews.com.
But Nicole has been sure from the start: "I've always known I was a girl," she told the Globe. "I think what I am aiming for is to undergo surgery to get a physical female body that matches up to my image of myself."
Her mother, Kelly Maines, who is 50 and works in law enforcement, went online to learn more and came across the Gender Management Service at Children's Hospital in Boston, founded in 2007 by endocrinologist Dr. Normal Spack and urologist Dr. David Diamond, the first of its kind in the Western hemisphere.
The clinic serves children with disorders of sexual development and physical deformities, as well as those with gender identity issues with a team of geneticists, urologists, endocrinologists and mental health specialists.
At about 12, Nicole was given puberty blockers to stop the development of secondary sexual characteristics like male body hair, which can later make sex reassignment surgery more painful and expensive.
Later in adolescence, she will begin estrogen treatment and continue on testosterone suppressers until she is 18 -- old enough for surgery.
After the testes are surgically removed, there will be no need for the hormone blockers. But the entire procedure will render Nicole infertile, which is why she continues counseling to help her make a final decision.
The majority of all children who express the belief that they are the wrong gender, will enter puberty and go on to identify with their biological gender, according to Spack.
"Of all little kids who are gender variant, 20 percent will stick with it," he said. "Over 80 percent will accept looking like Jonas and would push talk about cutting off [their penis.]"
That is why doctors wait for children like Nicole to show the first sign of puberty before giving them blockers and the treatments are reversible.
But giving a prepubescent child hormones of the opposite sex has permanent effects like halting their development, closing up growth plates. Using puberty blockers "buys us time, so they can extend the diagnostic phase," Spack said.
Spack said GeMS has sent a half dozen children all the way to sex change surgery from male to female. Using estrogen in combination with testosterone blockers allows them to develop curves and grow "normal" size breasts without implants.
Surgery is also sophisticated. "They have learned to use tissue to form the vagina and some surgery is so incredible even gynecologists have been a bit fooled."
Sensation tissue can also be preserved so male to female patients can experience orgasm. Even fertility may one day be resolved, he said.
"Nicole has a hopeful future," said Spack. "The field is growing faster than I am getting old. Who knows about the future of reproductive endocrinology."
The fact that Nicole and her brother are identical twins gives scientists a window into the causes of transgenderism. Though Nicole is the first in this clinic, twins like the Maines ones are not unknown.
"Obviously everything isn't DNA," said Spack. "Parents tell you identical twins are different. But what this means in terms of transgenderism altogether, we are in a primitive state of understanding this."
Several neurological studies from Europe show brain differences in transgender people, suggesting they may be "wired" differently. Spack said that he has noticed that about 10 percent of his patients display "something in the autistic spectrum, very mild, like Asperger's [syndrome]."
As for Nicole, Spack said her strong voice helped the family support her and eventually seek help. She has even been able to attend a summer camp for transgender children -- Camp Arunu' Tiq.
"She needed to push the envelope," said Spack, who now only consults on her case every few months. "I have this phenomenal image of her. I saw Nicole and other kids who had seemed reticent in my office playing the piano and doing dance numbers, just like at any other camp."
Spack, who once yearned to deliver babies, said he gets a special thrill working with transgender children like Nicole.
"It's sort of like being a midwife to a person who has the courage to give birth to themselves," he said.