American Society of Human Genetics Meeting and Alabama NF Walk

Last month, several colleagues from UAB attended the American Society of Human Genetics meeting in Orlando (ASHG). The ASHG is the primary worldwide professional membership organization for human genetics with the mission of advancing genetics research by promoting the exchange of research findings at annual meetings, advocating for research support, and enhancing genetics education for current and future professionals in the field.  Several faculty members from the UAB NF research program gave poster presentations at the meeting, including NF Program Genetic Counselor Ashley Cannon, PhD, MS, CGC, and Associate Professor of Genetics Deeann Wallis-Schultz, PhD, as well as several other members of our research team. These presentations served as an opportunity to bring attention to our role as a national leader in advancing innovative NF research initiatives.

Our program was again pleased to support the 4th Annual Alabama NF Walk, which occurred on November 5th in Veteran’s Park in Hoover. Held in cities across the nation, the walk serves as a key fundraising event 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. This year’s walk raised over $30,000 and gathered individuals and families from Alabama as well as surrounding states. To learn more about the Alabama Walk visit:

Muscle Involvement in NF1  

An area of interest that we haven’t discussed previously is whether there is a direct involvement of muscle in NF1.  The primary manifestation of NF1 involves nerves affected by the growth of tumors. Because nerves control muscles, one might expect some muscle weakness due to impairment of a nerve by neurofibroma growth.  For example, a plexiform neurofibroma located on a spinal nerve could result in weakness of muscle innervated by that nerve.

There is, however, evidence now that there can be muscle involvement that is not related to a nerve sheath tumor.  Many children with NF1 exhibit low muscle tone, which usually becomes apparent between the ages of 2 and 5. Low muscle tone results in muscles that feel looser or more lax than normal, although muscle strength is typically within normal limits. Some children with low muscle tone tire more easily as a result of the condition. Also, the bellies of some children may protrude and give the appearance of a potbelly. This protrusion is due to abdominal and spinal muscles that are laxer than normal, not as a result of being overweight in most cases.  Low muscle tone should not affect one side more than the other, and the problem usually gradually improves by adolescence. However, these individuals retain relatively poor coordination compared to their peers.

For a long time it was assumed that low muscle tone in children with NF1 could be due to a central nervous system problem related to neurological pathways to the muscles. In recent years, increased attention to this issue has resulted in studies of muscles in individuals with NF1, which have shown some abnormalities of the function of muscle cells themselves. These findings suggest that something may be occurring in muscle cells, although it is not known in what ways the NF1 gene is affecting the muscle.

Parents of children affected by low muscle tone often ask if anything can be done to improve the condition. Physical therapy is often the recommended approach for improving the muscle tone and strength. It is a safe and useful way to define the current level of muscle function and provide opportunities to gain strength and improve overall coordination when a child is young. There are ongoing studies focused on developing more specific treatments for low muscle tone. While these are promising for the future, physical therapy is the only current option for improvement of motor function, though in many children this improves only very gradually over a period of years.
This month, I’d like to address an issue that often arises in the minds of parents whose children have been newly diagnosed with NF1. These parents often ask when they should be concerned about an issue or symptom that they notice in their child. I don’t think parents should assume the task of being their child’s doctor and become hypervigilant about every potential issue. Instead, parents have the important role and responsibility of nurturing and caring for their child. However, it’s natural for parents to experience anxiety about possible complications of NF1, and we do want parents to be alert to any potentially serious complication that may develop. The key is in separating everyday aches and pains from important symptoms, and the central question becomes:  What are the complications that, if detected early, would allow for better outcomes for children with NF1?

Optic Glioma

A tumor of the optic pathway, or optic glioma, occurs in approximately 15% of children with NF1. These tumors usually occur early in life, between the ages of 18 to 24 months. While more than half of children with optic glioma have no symptoms, some children experience vision loss, usually between the ages of 2 to 6 years. Because very young children don’t complain of vision loss, the early presentation of these problems can be subtle. Some signs of possible visual impairment include: tripping over objects or having difficultly navigating physical obstacles; becoming fearful of walking down stairs; and holding objects closer than normal or sitting closer to a screen, such as a television or computer. While we recommend yearly eye exams for children with NF1, parents who recognize these possible signs of vision loss should make an appointment for an evaluation with an NF specialist or pediatric ophthalmologist.

Physical Growth

A physical feature that is common for children with NF1 is that head size tends to be larger than average. However, a sign of concern would be if the size of the head crossed percentile lines as it grew or became noticeably larger in a relatively short period of time. Also, vomiting and lethargy could be a sign of obstructive hydrocephalus, a condition of increased brain fluid pressure that is rare, but more common in people with NF1 and usually occurs in childhood or young adulthood.

Also regarding physical growth, some degree of short stature is common among children with NF1. Slow weight gain is also common, although falling off the growth curve or crossing percentile lines are a cause for concern that requires further evaluation. In some cases, a brain stem tumor or optic glioma can affect the functioning of the hypothalamus where appetite is controlled, resulting in weight loss.

Plexiform Neurofibromas

These tumors, which occur deep in the body and involve large branches of multiple nerves, are usually noticed in the first year of life. They appear as a painless soft tissue swelling of the arm, leg, or around one or both eyes or on the face. Plexiform neurofibromas are believed to be congenital in most cases, although they are not easy to see at birth. Swelling of the upper eyelid in the early years of life could be a sign of a plexiform neurofibroma around the eye, which can grow rapidly in childhood and cause significant disfigurement and interference with vision.  Enlargement of an arm or leg can also be an early sign of plexiform neurofibroma.   

Bone Dysplasia

This problem is an abnormality of a long bone, usually involving the tibia in the leg but also sometimes affecting the fibula as well as bones in the arms. Bone dysplasia sometimes presents as bowing of a leg in infancy, although this can be difficult to detect early because most infants have some normal leg bowing. By the time a child can stand, one can usually determine if dysplasia is present. An X-ray is performed to confirm the problem, and the child is referred to an orthopedist for treatment with a leg brace to prevent fracture. If a fracture does occur, it can be difficult to treat, which makes early detection of this problem important.

Developmental and Cognitive Issues

Some children with NF1 exhibit low muscle tone, which results in muscles that are less firm and seem weaker than normal.   This problem tends to improve over time, but it may evolve into some degree of poor coordination in adolescence and adulthood. Also, learning problems are present in approximately 50% of children with NF1, although this issue may not become apparent until the child has reached school age.  Children with NF1 may exhibit problems in maintaining attention, hyperactive behavior, and social immaturity.  In some, speech articulation may be affected.  Sudden onset developmental delay is not common in children with NF1.  If a child is failing to reach developmental milestones or displays signs of learning or cognitive problems, this is a cause for concern and further evaluation. 


I have mentioned the occurrence of headaches in children with NF1 in previous blogs.  Most typically these occur intermittently and may be associated with nausea, stomach aches, and vomiting.  These signs are suggestive of migraine, which seems to be more common in children with NF1 than in the general population.  Another cause of headaches in children with NF1 is Chiari malformation, in which the base of the brain extends below the foramen magnum, which is the space in the skull where the spinal cord connects to the brainstem.  This is also more common in children with NF1 than in the general population.  Many parents of children with NF1 and headaches worry that the headaches could be a sign of brain tumor.  For a brain tumor to cause headaches it requires that the tumor cause increased fluid pressure in the brain.  If this does happen, the headaches are usually severe, may wake the child from sleep, and are associated with severe vomiting.  A careful physical exam would reveal increased pressure on the optic nerve visible in an eye exam, and would be followed up with an MRI scan.  Fortunately, I find that this is an uncommon cause of headaches in children with NF1.
In news related to the UAB NF Program, I’d like to mention that that Department of Defense NF Research Program has issued a request for grant applications (RFAs) from investigators to support innovative, high-impact NF research.  Several of our faculty members have submitted proposals, and more updates will follow as the process moves forward.

Pain Related to NF1

In this month’s post, I think it would be helpful to discuss the issue of pain in the context of NF, other than headaches, which have been covered previously. Individuals with neurofibromatosis type 1, the most common form of NF, can sometimes experience pain related to the presence of neurofibromas, benign tumors that can grow on nerves throughout the body.  While neurofibromas are not typically painful, some people have pain associated with these tumors that may take a variety of forms. Cutaneous neurofibromas, which appear on the surface of the skin, can sometimes result in pain due to an event that causes pressure on the tumor, such as hair brushing.  These tumors can also become infected, which can be painful.  Subcutaneous neurofibromas, occurring under the skin, can be nodular and are usually pea-sized to marble-sized. Though not typically painful most of the time, they can be tender to the touch or pressure such as hair brushing or lying down. Subcutaneous neurofibromas on the scalp can also serve as trigger points for headaches by internally pressing on nerves and surrounding structures, causing pain.

Plexiform neurofibromas occur deep inside the body and are usually not painful unless causing pressure on internal structures. There are instances in which they can press on nerve roots, resulting in significant pain. Some individuals with NF1 develop a condition call dural ecstasia in which there is a ballooning of the membranes surrounding the spinal cord that can put pressure on surrounding nerves, resulting in pain in the lower back or legs.   This can be a very difficult condition to treat surgically, and may result in chronic pain.

Some adults with NF1 may also experience exquisite pain with pressure applied at the tips of fingers and toes due to the presence of glomus tumors that occur under the nail beds. Fortunately, this pain can be eliminated by removing these tumors surgically; however, many adults don’t associate this pain with NF and therefore don’t seek treatment. It’s important for patients and clinicians to be alert to this type of pain so that surgery can be performed if needed.

Malignant peripheral nerve sheath tumors, which occur in 10% of people with NF1, cause a nagging, unremitting pain that becomes worse over time. It’s important to recognize this type of pain so that an imaging study, such as an MRI and PET scan, can be performed to identify the tumor and recognize its malignant potential.  For this reason, people with NF should be alert to any unexplained and persistent pain.

Pain Related to NF2 and Schwannomatosis

Chronic pain can occur in individuals with neurofibromatosis type 2 due to nerve root compression by one of the two types of tumors associated with the condition, meningiomas and schwannomas.

People with schwannomatosis, the third distinct type of NF, usually experience excruciating pain, which is a hallmark of the condition. Surgical removal of schwannomas usually relieves pain, although surgery is not always feasible due to the location of the tumors. Interestingly, the pain tends to be out of proportion with the number and size of tumors. Small tumors can be surprisingly painful, which may indicate there is something inherent in the tumor that causes pain.

Pain Management and Signs to Seek Treatment

In mild instances of NF-related pain, over-the-counter medications, such as Ibuprofen, are usually indicated and can be effective. Pain due to nerve compression or dysfunction sometimes responds to the medicine gabapentin or other similar medications.  Also, pain management programs can be helpful in dealing with chronic pain for which there is not a treatment option available. These programs have extensive experience in helping patients achieve symptom relief while avoiding addictive drugs when possible.

In conclusion, it’s important for individuals with NF to understand the signs of when to seek treatment for pain, including: chronic or nagging pain that gets worse over time; neurofibromas that become noticeably larger; pain with pressure applied to the tips of fingers and toes; and localized pain, which may be an indication of nerve root compression.