Re-Cap of Successful NF Symposium and Plans for 3rd Annual NF Walk

Last month saw another successful annual NF Symposium, held for the first time at the Children’s Harbor Building at Children’s of Alabama on Saturday, August 27th.  Co-sponsored by UAB and Children’s Tumor Foundation (CTF), this half-day, free event, also known as NF Family Day, provided an invaluable opportunity for NF patients and families to hear a series of presentations on a range of NF-related topics presented by clinical experts.  A special program of activities was provided for the children in attendance, and our NF families also had an opportunity to learn about the range of services available at Children’s Harbor, a non-profit organization that supports seriously ill children and their families through education and counseling services. I opened the Symposium with an introduction to the features of NF as well as an overview of our research initiatives in the NF Program.  UAB Professor of Pediatrics and Director of Neuro-Oncology Alyssa Reddy, MD, provided an update of NF-related clinical trials currently in progress, and UAB Assistant Professor of Pediatrics Critical Care Michele Kong, MD, gave an interesting and informative talk on developmental issues in children (not just those with NF). Also, our NF Program Genetic Counselor Ashley Cannon, MS, PhD, CGC, presented the natural history of dermal neurofibromas, followed by Birmingham patient advocate Renie Moss’ review of advocacy, fundraising, and upcoming events. In addition to providing an opportunity for NF patients and families to gain important information about NF, it’s also rewarding to know that this annual event facilitates connections among patients and families that allow them to share their unique challenges, experiences, and concerns.

I also want to mention that plans are underway for another important NF event, the 3rd Annual Alabama NF Walk, which is scheduled for Sunday, October 16th, at 1 p.m. in Veteran’s Park in Hoover.  The purpose of the event is to raise funds for the Children’s Tumor Foundation (CTF), the major source of patient advocacy and research support for all forms of NF in both children and adults. Last year’s event raised more than $73,000 and registered more than 400 participants, which was a significant accomplishment for an event that was launched in our local area only two years ago.  We’re pleased that the NF Walk has continued to generate increased interest each year and has become a significant means of raising critical funds to support NF research focused on the development of breakthrough treatments. To learn more about the Alabama NF Walk or to register, visit

Brief Review of Mosaic NF1

In previous blogs, I’ve referred to the fact that some people have features of NF that are confined to a certain region or segment of the body. A possible explanation for the occurrence of isolated NF features in some individuals is mosaicism, caused by a genetic mutation of the NF1 gene that arises after conception and during early embryonic development. As a result, some cells in the body have the mutation while other cells do not.  The area of the body affected may be a cluster of cells in one region, such as an arm or leg, resulting in café-au-lait spots or a cluster of neurofibromas in one region of the body. Because genetic testing for NF1 using blood doesn’t always detect the mutation in people with mosaicism, the best method of diagnosing this form of NF is to perform genetic testing using a biopsy of affected tissues, either neurofibromas or café-au-lait spots.  

A question that often arises related to mosaicism is whether there may be features of NF present in the body that are not visible on the surface. In the majority of people with mosaicism, the outward manifestation is the only NF feature that is present, but we do remain vigilant for other manifestations that may occur internally. Unless specific symptoms are present, there is usually no need for imaging to detect tumors.

Another important question related to mosaic NF1 is whether it can be passed to a child at conception. An individual with mosaic N1 cannot have a child with the mosaic form of NF1. However, it is possible for someone with mosaicism to have a child with generalized NF1, in which every cell in the body has the NF1 mutation.  If we know an individual has a mosaic form of NF, we can offer prenatal counseling and genetic testing to assist in pre-conception planning.

Neurologic Exam

Continuing our discussion from last month’s blog about what to expect during an NF exam, I’d like to briefly review the components of the neurologic exam. First, mental status is evaluated by determining if the patient is awake and alert and able to understand and speak. For a child, this part of the exam involves an evaluation of developmental status, including a determination of whether the child can talk and follow basic commands in accordance with his or her age level. In addition, we evaluate the function of the 12 cranial nerves, which originate from the brain and brain stem and affect the head and neck.  Each nerve has a specific sensory or motor function. For example, the 3rd, 4th, and 6th cranial nerves are responsible for eye movements and could be affected either by neurofibromas or problems in the brainstem related to NF.  We also perform a visual assessment to evaluate functioning of the 2nd cranial nerve, the optic nerve, which carries visual information from the retina to the brain. People with NF may develop tumors on the optic nerve, called optic gliomas, that can cause loss of vision and can also affect hormone secretion in the pituitary gland that may lead to early onset of puberty. It’s important for children with NF to have a comprehensive eye exam yearly to check for symptoms of optic glioma.

Also as part of the neurologic exam, we evaluate the strength of the facial and jaw muscles, the tongue, and the neck and shoulders; muscle weakness in these areas may indicate a problem in the brain stem or a tumor on the nerve itself.  Next, we evaluate the peripheral nervous system, which involves an assessment of overall muscle strength as well as reflexes and coordination.  We look closely for asymmetry of motor strength, which could indicate the presence of a neurofibroma on the nerve as it exists the spine. Abnormal reflexes provide a possible indication that a tumor may be compressing the nerve or the spinal cord.  The last component of the exam is the sensory evaluation. Some individuals with NF have symptoms of neuropathy, or peripheral nerve damage, which may include numbness, tingling, or burning sensations usually in the feet and hands. 
Neurofibromatosis Symposium: Family Day 2016

Plans are finalized for the upcoming Neurofibromatosis Symposium to be held in the Bradley Lecture Center of the Children’s Harbor Building at Children’s of Alabama on Saturday, August 27th.  This will be the first time the Symposium will be held in Children’s Harbor, a non-profit organization that supports seriously ill children and their families through educational and counseling services; we’re pleased that our NF Clinic has formed a collaboration with Children’s Harbor to enable our families to take advantage of the services they provide.  Also known as NF Family Day, the NF Symposium is a half-day, free event, co-sponsored by UAB and the Children’s Tumor Foundation, that supports a key mission of our program in providing NF patients and their families with valuable information on a range of NF-related topics presented by clinical experts. 

Janice Crow with Children’s Harbor will discuss the services offered by the organization and will be available to meet with parents one-on-one during the Symposium to discuss educational needs. Also, a tour of the facility will be available later in the day for those interested. Additional presentations during the Symposium will include an overview of NF1, NF2, and schwannomatosis as well as activities in the UAB NF Clinic; an update on clinical trials; developmental difficulties for children with NF; the natural history of dermal neurofibromas and upcoming clinical trials; and a review of advocacy, fundraising, and upcoming events. For the convenience of our families, breakfast, lunch, and childcare will be provided. Children participating in childcare in the Children’s Harbor facility will have access to a variety of activities including art projects, video games, and board games. While there is no cost to attend, reservations should be made by August 24th by emailing or calling 205-996-2916.  The NF Symposium is an invaluable opportunity for NF patients and families, especially those facing a new diagnosis, to learn key information and answers to questions about neurofibromatosis. It also provides a unique forum for patients and families to connect with one another and gain understanding and strength through their shared experiences, challenges, and concerns.  We look forward to serving our NF patients and families again this year through hosting this meaningful and informative event. 

Neurofibromatosis Symposium:  Family Day 2016

Saturday, August 27th, 2016


08:00-08:30 a.m.                                Register/Breakfast

08:30-8:45 a.m.                                  Welcome – Dr. Bruce Korf

8:45-9:00 a.m.                                    Children’s Harbor/Educational Assistance – Janice Crow

9:00-10:00 a.m.                                  NF 101/Updates – Dr. Bruce Korf

10:00-10:30 a.m.                                Clinical Trials Update – Dr. Alyssa Reddy

10:30-10:45 a.m.                                Break

10:45-11:15 a.m.                                Developmental Difficulties – Dr. Michelle Kong

11:15 -11:45 a.m.                               Dermal Neurofibromas – Dr. Ashley Cannon

11:45-12:00 p.m.                                Advocacy, Fundraising, Upcoming Events – Renie Moss

12:00-12:30 p.m.                                Children’s Harbor Tour

12:30-1:30 p.m.                                  Lunch

1:30 p.m.                                             Closing Remarks

Applications of the CRISPR/Cas9 Gene Editing Technology

A question that frequently arises related to NF research is regarding the application of the gene editing technology CRISPR/Cas9 system. This technology allows investigators to “edit” the genome by targeting a particular gene sequence and changing it to something different. The technology has received a good deal of publicity lately, including a recent feature on the cover of TIME magazine. 

The system has immediate application for creating models of disease. For example, if an investigator wants to create a mutation in mice or stem cell lines, the CRISPR/Cas9 enables targeting of the NF gene and introduction of a mutation. Our NF research program is currently using the technology for this purpose.  The question is whether the technology could be used to restore the mutated gene back to normalcy. The challenge here is in targeting all the cells in the body. With a condition such as NF, in which the mutation causes the lack of production of a substance (neurofibromin) that affects growth of specific cells throughout the body, you would have to be sure to target every cell that could possibly form a neurofibroma. If you miss a cell that has the potential to form a neurofibroma, that particular cell could still grow into a tumor. For now, the technology does not enable correction of a mutation in every cell.  There is much left to be learned about how the CRISPR/Cas9 system might be applied in the treatment of neurofibromatosis, however, so the possibility of it therapeutic use is in consideration.

NF Extremities Examination

Turning back to our previous discussion about what to expect during an NF exam, I’d like to briefly review what NF clinicians are focused on during an examination of the extremities.  First, plexiform neurofibromas can affect the brachial plexus, a network of nerves that originate near the neck and shoulder and send signals from the spine to the arm and hand. Plexiforms can also affect the lumbar plexus, a network of nerves in the lower spine that send signals to the pelvis and legs. Some plexiform neurofibromas can cause infiltration of nerves in these areas that can compress the nerves and cause pain. In some cases, the presence of plexiform neurofibromas in these areas can cause a visible overgrowth of the extremity. In other cases, the problem presents with lower back pain. An MRI will confirm lumbar involvement. Due to the location in the body, these tumors are not surgically accessible; however, it is sometimes possible to perform surgery to help relieve pain. The other primary treatment option is pain management.

Another extremity-related problem that can occur is bone dysplasia, which is an abnormality of a long bone, usually involving the tibia in the leg but sometimes also affecting the fibula or even bones in the arm.  This problem sometimes presents as a bowing of the leg in infancy, although it can be hard to diagnose that early because most infants have some normal leg bowing. By the time a child can stand, one can usually determine if this problem exists. An X-ray is performed to confirm dysplasia, and the child is referred to an orthopedist for treatment with a leg brace to prevent fracture.   If the bone does fracture, it can be hard to treat. Also, surgery is difficult because the bone is not well formed.  For this reason, prevention of fracture is important when this problem exists.

Plexiform neurofibromas can also affect any part of the foot or hand. While it’s not possible to surgically remove all of the tumor, surgery can be performed to remove a portion of the tumor (debulking surgery).  Lastly, certain types of tumors discovered fairly recently, called glomus tumors, can occur under the nail beds of the fingers and toes in adults with NF. Although they are not easily visible, they are usually exquisitely painful with pressure applied at the tips of fingers and toes. Fortunately, they can be removed surgically to eliminate the associated pain. It’s important for NF clinicians and patients to be alert to this potential problem.
I’d like to begin with month’s blog with a special word of recognition for our NF Program Genetics Counselor, Ashley Cannon, MS, PhD, CGC, who has been named a 2016 recipient of the prestigious Francis S. Collins Scholars Program Award.  Ashley is the first individual in our program to have received this significant honor, which is designed to attract the highest level of talent to the field of NF1 by providing salary and research support to advance rigorous clinical translational research that will lead to improved treatment options for NF1.  The award is named in honor of Dr. Francis S. Collins, who led one of the teams that discovered the NF1 gene in 1990 and currently serves as the Director of the National Institutes of Health (NIH). It is Dr. Collins’ hope that the Scholars Award will encourage others to combine a career in patient care and research, as he did. Because Ashely is trained in and serves both as a genetic counselor and a neuroscientist, her work embodies the clinician-scientist role that Dr. Collins envisioned for the program.  As a Collins Scholar, Ashley’s work will focus on two primary areas.  In the patient care arena, she will utilize her training as a genetic counselor and a neuroscientist in working closely with patients to better understand the specific problems and challenges they face related to NF and develop methods to address these problems. In the area of research, she will be working on a clinical trial for dermal neurofibromas with the goal of developing new treatments. Our entire NF clinic team joins me in congratulating Ashley for this outstanding achievement, which is very exciting for our program. 

In another special recognition of a dedicated individual in our local NF community, Renie Moss, tireless patient advocate, was recently presented with the Volunteer of the Year Award by the Children’s Tumor Foundation (CTF) during the CTF Volunteer Leadership Council Meeting in Austin, TX.  Renie was recognized for her inspirational leadership and dedication to patient advocacy and increasing NF awareness nationwide as well as her unique spirit of caring and compassion for NF families. The NF community is very fortunate to have someone with Renie’s many talents dedicated to the cause of patient advocacy and education.

Re-Cap of NF Forum
Last month, 10 people from our NF program attended the annual NF Forum held in Austin, TX, which marks the largest group from our team to attend this meeting. The NF Forum is the largest worldwide meeting dedicated to NF, bringing together patients and families as well as more than 300 NF clinicians and scientists from around the world to discuss advances in patient care, treatment, and research.  The meeting provides an invaluable collaborative environment in which to exchange ideas and research findings with international clinicians and scientists working in the field of NF.  Several members of our team gave poster presentations summarizing research conducted as part of our NF research program. The meeting left all of us energized with new ideas and goals for our program.  One of the most interesting aspects of this year’s meeting was learning about new animal models that have been developed using pigs instead of mice.  The pig model replicates the features of NF1 more closely than the mouse model, providing significant research advantages.  We’re currently establishing a collaboration with one of the groups that developed the pig model and are hoping to incorporate these models into our research in the near future.

NF Genital Exam
In continuing our discussion of what to expect during an NF exam, I’d like to briefly review issues that could be detected during a genital exam. The most relevant potential problem we’re looking for is evidence of early or delayed puberty.  As clinicians, we’re looking for changes such as the appearance of pubic hair and an early growth spurt as indicators of precocious (early) puberty. Sometimes, precocious puberty occurs for no known reason, but usually it is associated with optic nerve tumors (optic glioma) that involve the nearby hypothalamus that controls hormonal production in the brain.  If signs of precocious puberty are found, we use MRI to check for the presence of an optic glioma and obtain hormonal studies.  We also arrange for referral to a pediatric endocrinologist.  Early puberty is difficult for children both emotionally and psychologically, and it causes them to be significantly taller than their peers at a very young age, but, because of premature closure of the growth plate, ultimate height attainment is shorter than normal. Precocious puberty can be successfully treated hormonally; if there is an optic glioma, sometimes that, too, requires treatment, though if there is no impairment of vision or evidence of progression, the optic pathway tumor may not require treatment.  Aside from precocious puberty, signs of puberty can also occur later than normal.  If delayed puberty is suspected based on a lack of physical indicators such as pubic hair and an adolescent growth spurt, we would also perform hormonal testing and refer to an endocrinologist.   

In some people with NF, plexiform neurofibromas can affect the genital region, sometimes causing an overgrowth of the genitalia in males and females. Surgical treatment can be performed in these cases to help manage the problem. In women, plexiform neurofibromas can also sometimes impinge on the uterus and cause issues during pregnancy that might require surgical treatment, though sometimes these are too large to be amenable to surgical resection.