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.

Planning the Upcoming NF Symposium

As part of our NF Clinic’s ongoing efforts to maintain a patient-centered focus, the NF Community Advisory Board was developed last year with the objective of providing input and direction regarding patient information, education, support, and coordination of care.  Comprised of NF patients and family members, the Board meets four times a year. During the Board’s second meeting of the year held last month, plans were discussed for the upcoming NF Symposium scheduled for August 27th. Also known as NF Family Day, this half-day, free event co-sponsored by UAB and the Children’s Tumor Foundation (CTF), provides valuable information to NF patients and families through a series of presentations given by clinical experts on a range of NF-related topics. The Board was very helpful in offering suggestions for this year’s Symposium, which will be held for the first time in the Children’s Harbor Family Center at Children’s of Alabama. Children’s Harbor is a non-profit organization that supports seriously ill children and their families through educational and counseling services.  Although the previous NF Symposia have been held at the Kaul Building in the UAB Medical District, the Children’s Harbor Building offers better facilities and parking for this type of event. Also, our NF Clinic has formed a collaboration with Children’s Harbor so that our NF patients and families can take advantage of the educational and counseling services they provide.

Enhanced Patient Exam Procedure in the NF Clinic

We’re pleased to announce the addition of Tammy Skelton, MSN, CRNP, NP-C, a certified nurse practitioner, to our team of specialists in the UAB NF Clinic.  Tammy is enhancing patient care by performing preliminary patient examinations after our certified genetic counselor, Ashley Cannon, MS, PhD, CGC, collects or reviews a patient’s history. After I review the history and notes from Tammy’s preliminary examination, I perform a more focused exam and talk to the patient/family. We then confer as a team regarding next steps. The feedback from our Community Advisory Board on this new procedure has been very positive. Our goal is to reduce the backlog of patients waiting to be seen in the clinic by streamlining the examination process. By having Tammy perform preliminary exams, we’re able to see more patients in clinic and spend more focused time with them. We’re hoping our NF patients and families will be pleased and that the new procedure will make us more accessible.

On another note, a team from our NF Program will be attending the Neurofibromatosis Conference in mid-June in Austin, Texas. We’re presenting several abstracts and participating in a series of workshops and presentations. Stay tuned for a re-cap of this important meeting in next month’s blog.

Review of the NF Abdominal Exam

To continue our discussion of what occurs during the typical NF examination, this month we will consider the abdominal portion of the exam. Because the abdomen is covered by a large expanse of skin, neurofibromas are usually very visible in this area; sometimes they are obvious, and other times they can be seen using a pen light to illuminate the skin from the side.  We’re also looking for masses, although it’s not very common to feel a mass through the skin. While the liver and spleen can be palpated, these organs aren’t usually involved in NF.

The two main abdominal-related concerns in people with NF are episodes of nausea and sometimes vomiting, which tend to occur mostly in children, as well as the lower GI problem of constipation.  Children with NF have a tendency to develop migraine headaches, and I find that stomachaches, nausea, and occasional vomiting are common presentations of migraines in children. Sometimes treating children for migraines can be effective in resolving gastrointestinal symptoms. Constipation also seems to be more common in people with NF, probably because the condition affects the nerves in the intestine.

It’s rare that a tumor is the cause of a GI problem. Although plexiform neurofibromas can occur in the abdomen, they are usually too deep to palpate and are mostly asymptomatic. Tumors can also occur in the wall of the intestine, but these are usually also asymptomatic, though sometimes they can cause obstruction or bleeding.  Gastrointestinal stromal cell tumors are more common in people with NF1 than in the general population. They present with abdominal pain and bleeding in the GI tract. It’s important that an individual with abdominal pain and blood in the stool be evaluated for this potential problem.  Lastly, some people with NF may develop a specific type of tumor on the adrenal gland called pheochromocytoma.  The most common presentation is high blood pressure, which is caused by increased secretion of the hormones epinephrine and norepinephrine.  Some people may also experience episodes of skin flushing and a racing heart.  If symptoms are present, a blood test is performed to determine the presence of elevated hormone levels. If this is confirmed, a 24-hour urine collection is performed to further detect the presence of increased hormones followed by a scan to identify the tumors. If they are found during a scan, careful surgical removal is required as the treatment.