The start of 2018 also marked my 15-year anniversary at UAB, having begun my tenure as Chairman of the Department of Genetics and Director of the UAB NF Program on January 2nd, 2003. At that time, the Department of Genetics consisted of only two full-time faculty members, subsequently merging with another department and increasing to 15 faculty. Today, the UAB Department of Genetics has grown to include 35 distinguished faculty members who continue to make significant contributions in clinical care, education, and research. Our program has also grown in scope over the past 15 years, with expanded patient care and initiatives in research and education. As part of a reorganization into adult and pediatric clinics, NF patients are now served at two distinct locations, including Children’s of Alabama and The Kirklin Clinic.  The NF Clinical Trials Consortium, for which UAB serves as the National Coordinating Center, is now in its third five-year funding cycle and is actively engaged in developing multiple new clinical trials for all forms of NF. In addition, our program has successfully secured NIH grants in genomic medicine focused on integrating genomics into diagnostic and therapeutic decision-making.  The department has three clinical laboratories, one of which – the Medical Genomics Laboratory – performs the most scientifically reliable and highest volume of NF genetic testing in the world. We also have an ongoing commitment to patient education through our annual support of key events such as the NF Symposium, NF Walk, and Rare Disease Genomics Symposium.

New Role as Chief Genomics Officer and Continued Role as Director of NF Program

Along with the significant growth our program has experienced over the past 15 years, the field of genomic medicine has continued to evolve since the completion of the Human Genome Project in 2003 that successfully sequenced the complete human genome. Since that time, our understanding of the role of genes in health and disease has greatly expanded, leading to the rapid growth of genomic medicine to provide individualized clinical care to patients. Genomic medicine uses an individual’s genetic profile to guide decisions about  prevention, diagnosis, and treatment.  UAB Medicine has committed to advancing research into genomic medicine through two initiatives aimed at collecting health data from participants to determine the impact of lifestyle, environment, and genomic profiles on a variety of health conditions.  UAB has launched the Alabama Genomic Health Initiative ( in collaboration with HudsonAlpha Institute for Biotechnology. We have been actively involved in recruiting participants in support of this initiative’s goal to enroll 10,000 individuals in our state over the next five years to determine how genomic information correlates with health status and risk of disease.  We are also the hub of a regional network as part of the NIH All of Us research program (, which ultimately will recruit 1 million volunteers across the country.  Local enrollment in this program will begin soon.

In support of UAB Medicine’s commitment to implement precision medicine across all clinical programs, I have recently been appointed to the new role of Chief Genomics Officer for UAB Medicine, with the responsibility for establishing clinical programs in genomic medicine across the UAB Health System. This role also involves providing training and education to clinicians in the use of clinical tools to enable the use of genomic information in making diagnosis and treatment decisions. Because of this new role, I’ve stepped away from my position as Chairman of the Department of Genetics, as relinquishing the administrative responsibilities involved in that position will allow more time for me to focus on these new initiatives. I’ll continue to serve as a professor in the Department of Genetics and will also continue in concurrent positions as Associate Director for Rare Diseases in the UAB Hugh Kaul Precision Medicine Institute and as Co-Director of the UAB-Hudson/Alpha Center for Genomic Medicine.  From the perspective of the NF Program, nothing changes, as I’ll continue to direct the program, with ongoing involvement in clinical trials and research initiatives in developing genomic therapies. Also, I will continue to see patients in the NF Clinic with a continued commitment to maintaining the highest standards of clinical care.

2018 NF Symposium/NF Family Day Coming in April

The annual UAB NF Symposium, also known as NF Family Day, is scheduled for Saturday, April 7th, in the Bradley Lecture Center of the Children’s Harbor Building. This year’s keynote speaker will be New York University neuro-oncologist Kaleb Yohay, M.D., who will give a presentation about the role of alternative medicine in the treatment of NF. This annual event serves as a forum for NF patients and families to hear a series of presentations about a range of NF-related topics from clinical experts and also provides a means for establishing connections with other NF families. Event registration information is coming soon; for more information, please contact Ashley Cannon at  or Renie Moss and

Newly Identified NF Mutation/Phenotype Correlation

Previously, I’ve discussed the ongoing efforts of the UAB Medical Genomics Laboratory to determine correlations between physical manifestations of NF (phenotype) and specific mutations in the NF1 gene (genotype). More than 3,000 mutations have been identified in the NF1 gene, and there are a few examples in which a specific mutation can be correlated to certain NF symptoms.  The January issue of the American Journal of Human Genetics (Am J Hum Genet. 2018 Jan 4;102(1):69-87. doi: 10.1016/j.ajhg.2017.12.001. Epub 2017 Dec 28.) features a paper from the UAB group and multiple collaborators, led by Dr. Ludwine Messiaen, that identifies a cluster of mutations in the NF1 gene that are associated with a relatively severe set of NF complications. This represents an example of a correlation between specific mutations and certain manifestations of NF.  It is known that most NF mutations turn off the gene, thereby destroying its function; there is no particular phenotype associated with these mutations, except the typical features of NF.   However, there are a handful of mutations where there is some ability to predict the phenotype. Identifying a correlation between a mutation and phenotype can be clinically valuable because certain complications can be anticipated with the potential of managing the condition more effectively. Also, a correlation provides information about how the gene works and may lead to answers regarding why some mutations result in a large burden of internal tumors but not many cutaneous neurofibromas, such as the mutations described in the recently published paper. With more than 3,000 NF gene mutations representing the largest repository in the world, the UAB Medical Genomics Laboratory, directed by Ludwine Messiaen, Ph.D., is in the best position for determining additional mutation/phenotype correlations. In 2016, using the repository of mutations and a catalogue of phenotypes (symptoms) in NF1 patients, Dr. Messiaen and her colleagues identified only the third genotype/phenotype correlation so far found for NF1. Some of these newly identified mutations are being reproduced in animal models, such as mice, rats and pigs, to observe the manifestations of NF correlated with these mutations. Also, we are developing a cell culture system that will help us to determine the way specific mutations alter function within the cell.   These studies will help us to classify the ability of specific mutations to cause NF1, and also will provide a system to test new approaches to treatment.
Highlights in Patient Care and Education and Plans for Upcoming Year

As the year draws to a close, I’d like to highlight significant accomplishments and events in the UAB NF Program during 2017 and provide a preview of plans for the upcoming year in patient care, education, and research.  It has been more than a year since the NF Clinic’s relocation to two distinct sites in the UAB Medical Center District as part of a reorganization into adult and pediatric clinics, and the change continues to reap benefits.  Patients seem to be pleased with the new facilities and improved logistics, including more convenient parking. The most significant benefit for our patients is the streamlined, integrated care that is provided in the new clinic locations that enable imaging, lab tests, and consultations with a range of specialists to occur in one location. We’re pleased that our patients are benefitting from this new structure and that our hopes seem to have been realized for improved convenience and integration of care. 

As part of our ongoing commitment to patient education and support, our program co-sponsored, with the Children’s Tumor Foundation (CTF), another successful NF Symposium at the Children’s Harbor Building at Children’s of Alabama in August. Also known as NF Family Day, this annual event serves as a forum for NF patients and families to hear a series of presentations on a range of NF topics from clinical experts as well as  provides a meaningful opportunity for NF families to connect with others sharing the same journey. Our program was also pleased to again support the 4th Annual Alabama NF Walk held last month in Veteran’s Park in Hoover. Held in cities across the nation, the NF Walk is an important 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.

Another highlight for our program this year was our participation in the Rare Disease Genomics Symposium, held in March at UAB, which is an event designed to share information about the role of genomics in the diagnosis and treatment of rare diseases with healthcare practitioners who are non-genetic specialists. While the event was not specific to neurofibromatosis, NF1 is a rare disorder that benefits from diagnostic and therapeutic approaches used in the management of other rare disorders.  The Symposium serves as an important forum for increasing awareness of rare disorders and educating faculty and clinicians at UAB and in the community about the role of genomic medicine in the diagnosis and management of rare diseases.  This year’s Symposium featured a panel discussion led by parents of children with rare diseases as well as an art exhibit showcasing works that depict people with genetic conditions in a humanistic way.  Next year, the Symposium will be a two-day event with the first day designed for professionals and the second day focused on families.

In addition to lending our continued support to the NF Symposium, NF Walk, and Rare Disease Genomics Symposium during the upcoming year, we also plan to increase patient engagement through continuing work begun this year on the development of a smart phone app.  This app will allow patients to become more involved in several aspects of their care and enhance their interaction and experience with the clinic.

Re-Cap of 2017 Research Initiatives and a Preview of 2018

The UAB NF Research program has been actively engaged in basic and preclinical research as well as clinical trials focused on identifying and developing effective therapies for people with NF. Our primary research focus is the development of therapeutics targeted at specific mutations. The UAB Medical Genomics Laboratory is a world leader in genetic testing and medical diagnosis of NF, performing the most scientifically reliable, leading-edge genetic testing currently available for the diagnosis and characterization of mutations for NF1, NF2, and schwannomatosis, with the highest volume of NF genetic testing in the world. The Medical Genomics Laboratory is engaged in ongoing efforts to determine correlations between physical manifestations of NF and specific mutations in the NF1 gene.  This research could provide a framework for determining the extent to which complications of NF are predictable.

Continuing our efforts in the development of animal models, we have developed several additional mouse models with specific NF mutations, some of which have been identified in our own patients. This offers the possibility of a personalized medicine approach to treatment that will remain an increased area of focus for our program in the upcoming year. These models enable our scientists to study the NF disease process as well as the effectiveness of potential drug treatments. Also in the area of preclinical research, we have developed a method of expressing the NF1 gene in a cellular system. This was accomplished by deleting the normal NF1 genes in these cells and replacing them with a mutated gene, allowing us to investigate the effects of a mutation on cells. A scientific poster summarizing our development of this model won first prize at the annual NF Conference last June.  We expect that the model system will yield further information about the NF disease process that will help guide the development of targeted therapeutics.

Additionally, we are conducting a clinical trial targeting cutaneous neurofibromas using the investigational drug called selumetinib. Cutaneous neurofibromas, which are common in adults with NF1, are benign tumors on or in the skin. This trial is actively recruiting study participants, and more information regarding the trial can be found at: (study number NCT02839720).

In support of our continued focus on the development of genome-guided therapies, we have also responded to several RFAs for research funding focused on genome-guided therapeutics with an emphasis on identifying approaches that will allow function to be restored to a non-functional gene or gene product. Our research program was the first to concentrate in this area several years ago, and now this approach is gaining increased attention from others in the scientific community.

Finally, last year we applied for renewal of our Department of Defense grant to fund the NF Clinical Trials Consortium.  This grant was approved, and the Consortium is now into its third five-year funding cycle.  We are in process of developing multiple new clinical trials for all forms of NF, including NF1, NF2, and schwannomatosis, and expect to be announcing the launch of the first trials very soon in the new year.

In summary, this has been a very busy year in the UAB NF Program, and next year promises to be at least as active.  I am grateful to our many supporters, and to the patients and families we serve for their confidence in our care.  I wish everyone a very restful and happy holiday season and look forward to reporting on our progress in the New Year! 
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.