Neurofibromatosis type 1 (NF1) is a genetic condition that results in the formation of neurofibromas, a type of nerve tumor that forms on or under the skin. Attached to nerves throughout the body, these tumors are usually benign, but can become cancerous and therefore require lifelong monitoring.
A rare genetic disorder, NF1 occurs at a rate of about one in every 2,600 people. While symptoms are usually mild to moderate, the condition can also be severe, such as what twin sisters Melissa Romberg and Michelle Paixio experience.
Symptoms of NF1 are often noticeable at birth, and usually appear during childhood. In addition to the neurofibromas, symptoms of NF1 include:
- “Café au lait” spots—flat, light brown spots on the skin. More than six spots suggest the presence of NF1
- Freckling in the armpits or groin
- Tiny bumps on the iris
- Bone deformities
- Optic tumors
- Learning disabilities
- Larger than average head size
- Short stature
NF1 is an inherited condition and is therefore present at birth.
“NF1 is autosomal dominant, which means it’s inherited in 50 percent of people with the gene,” explains Faith Barnett, MD, PhD, a neurosurgeon at Scripps Clinic. “If one of your parents has it, there’s a 50/50 chance you will have it too.”
In the twins’ case, their mother also has NF1, but never knew it. “My mom was finally diagnosed with NF after I was,” Michelle says. “Hers was milder than mine and my sister’s, so she didn’t know she had it. She had balance and hearing issues, which we now attribute to the NF.”
As for the next generation of the twins’ family, Michelle says, “My son is 22 and he has been ruled out for NF. My daughter is 26 and is a carrier of the gene, which means she doesn’t have the tumors, but she can still pass it on if she has kids. I do have a granddaughter who is being monitored for NF, but she’s only 5 and it’s too soon to tell. It’s usually puberty when tumors start to develop, because of hormones, so we won’t know for a while.”
For Melissa, it’s a watch-and-wait situation with the youngest of her three sons. “One of my three boys — the 13-year-old — has the NF gene and the café au lait spots,” she says. “You have to have so many spots to be diagnosed with it, so his pediatrician monitored the size and width of his spots as he was growing up. Now, we just hope he doesn’t get the tumors like we have. I don’t want him to suffer.”
For patients like Michelle and Melissa, who suffer from extreme chronic pain due to NF1, hope for relief has been limited to surgery and pain management. Now, there’s a new hope on the horizon in the form of an oral medication called Koselugo (selumetinib), which was approved by the FDA in April 2020 for the treatment of NF1 in patients age 2 and up.
“This is the first medication for the treatment of patients with NF1, a disabling and uncomfortable condition that until now has only been treated with surgery or radiation,” explains James Mason, MD, a hematologist and oncologist with Scripps MD Anderson Cancer Center and Scripps Clinic. “It interferes with the cellular pathway and inhibits cellular growth.”
Dr. Mason explains that until now, the medical community did not know exactly how to approach NF1. Now, however, thanks to cancer research, there’s a greater understanding about how to treat neurofibromas.
“It wasn’t reasonable to treat noncancerous neurofibromas with chemotherapy when they could be approached with surgical precision,” he says. “But this is an exciting new therapy. It has been shown to have a response rate in two-thirds of patients, in whom the tumors either get smaller or stop growing altogether.”
Dr. Mason cautions that clinical studies of this new medication have been done only on pediatric patients, and that it’s not without side effects. An oral medication taken twice daily, it can cause vision problems as well as gastrointestinal and cardiac issues.
Still, he says, for people like Michelle, who is taking the medication, “it represents a step toward the medical treatment of this very difficult inherited condition. It’s exciting to have something to give folks with NF1 other than surgery — you can’t operate on the dozens, hundreds or thousands of tumors they have. For patients who don’t have a lot of side effects, it’s an easy medication, and it will hopefully stop the progression of the disease and greatly improve the quality of their life.”
Dr. Barnett is also hopeful that this new medication will be a beacon of light for her patients like Melissa, Michelle and all others with NF1.
“For the treatment of NF1, we have surgery and sometimes radiation, which is the mainstay; watchful waiting; and now this third category — the new medication that Dr. Mason has taken on to try to treat these patients. They all work in concert with each other,” she says. “It’s really important that we work as a team because we do want to avoid surgery when we can. Sometimes, surgery is the easiest; other times you have to spend a year recovering from it. This opens up a new treatment modality, which is a really wonderful thing to offer these patients.”