In late September, several colleagues from the UAB NF Program participated in the 2019 NF Conference in San Francisco organized by the Children’s Tumor Foundation. The meeting is the largest international gathering of NF scientists and clinicians and is an important forum for several hundred participants from diverse scientific and clinical backgrounds to share knowledge and encourage collaboration with a focus on improving outcomes for all forms of NF. Several investigators from the UAB NF research program gave poster presentations summarizing our dug discovery initiatives and progress in clinical trials, including Robert Kesterson, Ph.D., Deeann Wallis, Ph.D, and David Bedwell, Ph.D. I participated in a panel discussion about differences in the way clinical care for NF is provided internationally, including speakers who discussed the approaches to care in Asia, Europe, South America and the U.S. The discussion focused on examining the effectiveness and strengths of various approaches to care in these different regions of the world.
Also, several colleagues from our program attended the American Society of Human Genetics (ASHG) meeting in Houston in October. This annual meeting is the largest conference of human genetics in the world and provides a forum for presentation and discussion of the most current science in all areas of human genetics. UAB investigator Deeann Wallis, Ph.D., from our NF research program presented a poster regarding her work in correcting NF mutations in model systems using a technique called exon skipping, which causes cells to skip over mutations in the genetic code while potentially still producing a functional protein.
Our program was again pleased to support the 7th Annual Alabama Children’s Tumor Foundation NF Walk that was held at the Tuscaloosa Buddy Powell Pavilion on November 2nd. The walk is held in cities across the nation as a fundraising event for the Children’s Tumor Foundation (CTF). This year’s walk raised more than $22k and gathered individuals and families from Alabama as well as surrounding states.
In NF clinic news, we are working to incorporate neuro-oncology into the clinic for both pediatric and adult patients to further enhance our multidisciplinary approach to care. Neuro-oncologists are familiar with many of the new treatment options available for NF, and our patients will significantly benefit from this additional expertise within our clinic.
Vascular Issues
Completing our review of the pediatric NF clinical care resource, several cardiac and vascular problems associated with NF1 are discussed. Regarding cardiac abnormalities, approximately 2% of children with NF1 have a congenital heart defect. The most common is pulmonic stenosis, which is a narrowing of the artery from the heart to the lungs that can result in a heart murmur as well as problems with exercise tolerance. Other cardiac abnormalities can include atrial septal defect, a hole in the wall between the heart’s upper chambers, and hypertrophic cardiomyopathy, which is a condition in which the heart muscle becomes thickened and has difficulty pumping blood. It seems that a complete deletion of the NF1 gene increases the risk of these cardiac abnormalities, and individuals with the NF1 gene deletion should be screened for cardiac problems. Also, newborns with NF1 should be examined for signs of a congenital heart defect.
Beyond the heart, blood vessels can also be affected in individuals with NF1. A condition called renal artery stenosis, a narrowing of the artery that carries blood to the kidney, is an important cause of hypertension in children and young adults with NF1. The kidneys control blood pressure by regulating the amount of water excreted from the body, and restriction in blood flow causes the kidneys to misinterpret this as low blood pressure in the body. In response, the kidneys release hormones that raise blood pressure and result in hypertension. It’s important to monitor blood pressure in people with NF1 beginning in childhood. If renal artery stenosis is found, it is treated with medication or stenting of the vessel to increase blood flow.
Arteries to the brain can also be affected in people with NF1. Moyamoya syndrome is a rare vascular disorder in which the internal carotid artery to the brain becomes blocked or narrowed, reducing blood flow to the brain. In response to the blockage, which develops very slowly, tiny blood vessels open up in the brain in an attempt to restore blood flow. The word “moyamoya” means “puff of smoke” in Japanese (the condition was first described in Japan, among children who did not have NF1), which describes the appearance on an angiogram of the cluster of blood vessels formed that compensate for the carotid artery blockage. Moyamoya occurs with increased frequency in children with NF1 and is especially common among children exposed to radiation therapy to the brain for treatment of a brain tumor. For this reason, we try to avoid use of radiation therapy for treatment of brain tumors in children with NF1 whenever possible.
It is possible for blood vessel occlusions to develop anywhere in the body in those with NF1. Sometimes the blood vessel walls can become weakened and hemorrhage, although this is rare in individuals with NF1 and, if it occurs, it is typically in adults. The guidelines are open-ended about screening for these problems, although imaging is indicated if symptoms are present.
Gastrointestinal Problems
Constipation in those with NF1 seems to be more common than in the general population and is commonly treated with dietary modification and the use of stool softeners. Also, abdominal pain, with or without vomiting, and accompanied by headache, can be an indication of abdominal migraine and is treated with medications for migraine.
Neurofibromas can develop in the walls of the intestine, causing bleeding and obstruction, although this is rare. Also, gastrointestinal stromal tumors (GIST) can cause bleeding and pain in patients with NF1. It’s important to be alert to GI bleeding and pain so that the appropriate diagnostic screening can be performed.
Lastly, the guidelines emphasize the importance of children with NF1 having a medical home with an NF physician who can follow them and make referrals to other specialists when needed. Because there are more NF clinics for children than adults in the U.S., transition of care can be difficult for pediatric patients once they reach the age of 18. The UAB NF Clinic is a combined pediatric and adult clinic, which provides continuity of care for pediatric patients as they grow up.