In New York, there are there are two Children’s Tumor Foundation-designated Comprehensive Neurofibromatosis Clinics dedicated to improving clinical care for those affected by neurofibromatosis (NF). One of those is led by Gurcharanjeet “ Bonnie” Kaur, MD, a pediatric neurologist and neuro-oncologist at NewYork-Presbyterian and Columbia. Under her leadership, the program provides multidisciplinary care to children, young adults, and adults with NF.
Below, Dr. Kaur discusses the different forms of NF, diagnosis and treatment, and NewYork-Presbyterian and Columbia’s unique approach to managing these patients.
What is neurofibromatosis?
NF is a group of genetic disorders that predisposes patients to develop brain, spinal cord, and skin tumors. The three main types – neurofibromatosis 1 (NF1), neurofibromatosis 2-related schwannomatosis (NF2-SWN), and schwannomatosis (SWN) – differ in their diagnosis and management, and genetic mutations. NF1 is caused by changes in the NF1 gene on chromosome 17 whereas NF2-SWN is caused by changes in the NF2 gene on chromosome 22, and SWN is caused by changes in the SMARCB1 or LZTR1 genes.
What are the differences between the types of NF?
NF1, also known as von Recklinghausen disease, is typically diagnosed during early childhood and is one of the most common genetic disorders, affecting approximately 1 in 3,000 children. Fifty percent of cases are inherited and the other 50% are sporadic. NF1 is characterized by the appearance of café-au-lait spots on the skin. However, these brown spots can also occur in the healthy population, which contributes to underdiagnoses of the condition.
Other signs and symptoms of NF1 include:
- Appearance of multiple cutaneous neurofibromas
- Bone deformities
- Freckling in the armpits or groin
- Appearance of growths on the iris
- Optic pathway gliomas
As opposed to NF1, NF2-SWN is less common and characterized by benign, slow-growing tumors on the cranial, spinal, and peripheral nerves, including schwannomas, meningiomas, and ependymomas. Diagnosis of NF2-SWN is typically based on the presence of bilateral vestibular schwannomas. NF2-SWN symptoms are typically first noticed in the young adults and adults. In addition to tumors, people with NF2-SWN may also experience vision problems and peripheral neuropathy.
Because NF can cause other issues, it’s key to detect the condition and diagnose it early to give them the best future possible.
— Dr. Bonnie Kaur
SWN is the rarest form of NF and genetically distinct from NF1 and NF2-SWN. The signs and symptoms overlap with NF2-SWN. In those with schwannomatosis, schwannomas and meningiomas often show no symptoms. Other signs and symptoms include chronic pain, numbness, tingling, or weakness in the fingers and toes, and loss of muscle function.
How is NF diagnosed?
If a physician notices that a patient has six or more café-au-lait spots of varying sizes - >0.5cm in pre-pubertal children and >1.5cm in post-pubertal children – along with a combination of the other signs and symptoms, they should be thinking about genetic possibilities that could cause multiple birthmarks and refer them to a NF clinic like the one at NewYork-Presbyterian and Columbia.
Café-au-lait spots are one of the hallmark symptoms of NF.
Most patients are diagnosed with NF1 by the time they are eight years old; however, we tend to see a lot of adults who never knew they had neurofibromatosis because, aside from the spots on their skin, they had no other symptoms. Because NF can cause other issues, it’s key to detect the condition and diagnose it early to give them the best future possible.
What goes into the decision-making about treatment for NF patients?
Our goal for their care is to manage their comorbidities and treat the tumors when they become symptomatic. General management for NF patients involves routine imaging surveillance to monitor tumor growth or new tumor formation; symptom management; and genetic counseling.
In patients with tumors, surgery to remove large or symptomatic neurofibromas may be necessary, and chemotherapy or radiation may be used for the optic gliomas. Many NF1 patients need orthopedic management of their skeletal deformities. NF2-SWN patients typically need regular audiological evaluations and interventions. Patients with SWN often require pain management.
How does NewYork-Presbyterian and Columbia approach the management of NF patients?
It’s very important to me to bring care to our patients’ doorsteps. Our unique location allows us to serve an incredibly diverse, underserved population in Washington Heights, Inwood, and the surrounding neighborhoods. We recently opened a clinic in Tarrytown, NY, which has a state-of-the-art MRI facility, to improve access to care for patients who live in upstate New York.
The complex care that NF patients require is why receiving treatment at a clinic like the NF program at NewYork-Presbyterian and Columbia is so important. We cross the division lines daily for these patients and bring together all of the subspecialists under one roof to coordinate care across the patient’s lifespan.
— Dr. Bonnie Kaur
Because NF can impact different bodily systems and also cause cognitive disabilities and developmental delays, patients with NF often need to be followed by additional specialists, including those in genetics, neurosurgery, neuropsychology, dermatology, ophthalmology, endocrinology, oncology, orthopedics, and other areas. For example, ophthalmologists often help us diagnose patients with optic pathway gliomas and follow them very closely, at times every six months or annually. Dermatologists help us with monitoring the café-au-lait spots and the skin nerve tumors as they change and evolve from benign to low grade or something that requires closer monitoring.
The complex care that NF patients require is why receiving treatment at a clinic like the NF program at NewYork-Presbyterian and Columbia is so important. We cross the division lines daily for these patients and bring together all of the subspecialists under one roof to coordinate care across the patient’s lifespan.
What innovations do you anticipate seeing in the future for NF treatment?
Although there is no cure for NF, I am optimistic about the future of treatment for the disorders. The first medication for NF1 was approved in 2020 and we currently prescribe that medication to eligible patients. For NF2-SWN, we have an open clinical trial that provides patients with access to therapeutics that are in the early stages of discovery. We’re also looking at using novel technologies that are used in other specialties, like magnetic resonance elastography, which could hopefully enable us to predict the transformation of tumors from low grade to high grade ahead of time.
My hope is that we are able to raise the bar and develop therapeutics that are going to be the most effective and have the least amount of toxicity for our patients so that they can continue to live near normal lives.
— Dr. Bonnie Kaur
We are also working on a clinical trial to use focused ultrasound (FUS), a noninvasive technology that has potential to improve quality of life for those with NF by alleviating the plexiform neurofibroma-related pain and the need for surgery.
At NewYork-Presbyterian and Columbia, we have cutting-edge researchers who are working to find new therapeutics, new treatment delivery methods, and more. My hope is that we are able to raise the bar and develop therapeutics that are going to be the most effective and have the least amount of toxicity for our patients so that they can continue to live near normal lives.
