In early November, several colleagues from the UAB NF Program will attend the 2018 NF Conference in Paris organized by the Children’s Tumor Foundation. Although the meeting is usually held in the U.S., CTF has partnered this year with the European NF Conference to further promote and encourage international scientific collaboration. Established in the 1980s, the annual NF Conference represents the largest meeting of NF scientists and clinicians and serves as the global forum for several hundred participants from diverse scientific and clinical backgrounds to encourage collaboration and advance research for all forms of NF. Our UAB group will present at least one platform presentation, as well as several poster presentations, summarizing our drug discovery initiatives and progress in clinical trials. We look forward to participating in this important scientific meeting and will review highlights of the event in a subsequent blog post.

Psychiatric and Neurocognitive Issues

In this last installment of our review of the ACMG practice resource, I’d like to first discuss some psychiatric and neurocognitive issues associated with NF in adults. It is well recognized that cognitive problems occur in at least 50% of children with NF, including learning disabilities and attention-deficit disorder (ADD).  However, less attention is paid to cognitive problems in adults with NF, although many individuals have neurocognitive issues that persist beyond childhood. One of the most common psychiatric problems in adults with NF1 is depression, which is sometimes related to cosmetic disfigurement or chronic medical problems, but this probably is not the only explanation; it’s uncertain whether NF1 has a primary effect on brain function that increases the risk of depression. Because of the prevalence of depression in people with NF, it’s important to pay attention to signs of depression that might include: irritable mood; feelings of sadness or emptiness; overeating or loss of appetite; changes in sleep patterns; difficulty concentrating; persistent fatigue; feelings of guilt or helplessness; and suicidal thoughts. Neurocognitive problems such as learning disabilities and attention-deficit disorder (ADD), which are common in children with NF1, often persist into adulthood. More research is needed to determine how these problems affect adults with NF1, as most studies have focused on the pediatric population. Clinicians are advised to be aware of the potential for neurocognitive and psychiatric problems in adults with NF1.  

Headache, Polyneuropathy, and Glomus Tumors

Another common problem in adults with NF1 is headache, which is often a component of migraine.  These headaches, usually throbbing in character, seem to be more common in people with NF1 than in the general population.  They can last several hours and cause extreme sensitivity to light and noise. While over-the-counter medications can be effective in treating occasional migraines, prescription medications are sometimes required to manage frequent migraine headaches. This includes not only medications to treat an ongoing headache, but also medications that can help to prevent them.  Because the occurrence of headache in people with NF1 is underreported and underappreciated, clinicians should be vigilant in discussing headache frequency and treatment options with patients.

Another problem addressed in the ACMG practice resource is polyneuropathy, which is an impairment of multiple nerves that affects approximately 2% to 3% of people with NF1. This condition usually presents as numbness or tingling in the hands and feet. While it doesn’t usually cause pain, it can predispose an individual to injury due to the lack of feeling in the extremities. Also, some adults with NF1 may experience severe pain with pressure applied to the tips of fingers and toes due to the presence of glomus tumors that occur under the nail beds. Most people with this problem don’t associate the pain with NF and therefore don’t seek treatment. Fortunately, these tumors can be successfully removed surgically, eliminating the pain. Therefore, it is important for clinicians and patients to recognize this type of pain so that surgery can be performed if needed. Pain related to NF can occur anywhere in the body, often, but not always, due to a tumor.  As we have discussed in the past, sometimes pain can be a sign of malignant change, so it is important to report persistent pain to a physician for further evaluation.   

Pregnancy and Contraception

Women with NF often report a progression of cutaneous neurofibromas during pregnancy.  This also occurs in both males and females during puberty, resulting in speculation about a possible hormonal link to the growth of neurofibromas. Because oral contraceptives contain a combination of progesterone and estrogen, many women with NF are concerned about whether it’s safe to take oral contraceptives.  There is no clear evidence that oral contraceptives contribute to the growth of neurofibromas in women with NF, though the issue is difficult to study, especially given the various formulations in use.   A woman with NF needs to balance the potential risks and benefits of oral contraceptive use, and should discuss the question with her physician.  As to other risks of pregnancy, problems such as high blood pressure, pre-eclampsia and fluid balance problems may occur more often in women with NF, although these problems require further study.  These risks warrant close monitoring during pregnancy by an obstetrician who is familiar with NF.

Another common pregnancy-related concern is whether epidurals administered prior to delivery are safe for women with NF. Although there are few studies related to the safety of epidurals in women with NF, the general feeling is that the procedure is not dangerous. While some people may be concerned about the presence of spinal neurofibromas, the ACMG group did not feel that it is necessary to perform imaging for spinal neurofibromas prior to the administration of anesthesia unless there are specific concerns about the presence of tumors (as from prior imaging or clinical signs).

Lastly, a couple in which one partner has NF1 needs to be aware of the 50% risk of transmission the NF1gene change to any offspring. This risk should be considered in family planning along with the fact that the wide variability of NF, even within families, means there is no way to predict the severity of NF in an individual. It is possible to do prenatal diagnosis of NF1, which first requires identifying the genetic mutation in the mother or father. The first method involves obtaining a fetal tissue sample through amniocentesis at 15-18 weeks of pregnancy to determine if the child has the genetic change. Another method involves chorionic villus sampling at 10-12 of pregnancy to identify the genetic change. A genetic counselor, who has specialized training in medical genetics and counseling, can provide information about specific tests available to couples regarding genetic risks and options to manage those risks.