Most newborns that have the neurofibromatosis gene mutation show few or no signs. Cafe-au-lait spots are usually noticed in the first few weeks of life, or may appear earlier. Their absence in a newborn that is at risk of inheriting NF1 from a parent is not a reliable indication that the baby has not received the NF1 gene, since the spots may show up later. However if the child has NF1, you would expect to see cafe-au-lait spots by the age of 6-12 months.

Neurofibromas are not often found in infancy. One exception is the plexiform neurofibroma. This is a neurofibroma which affects multiple branches of a nerve, usually a fairly large nerve. Occasionally, such plexiform neurofibromas are noticed in the newborn period, where they may appear as a soft swelling under the skin. Not finding a plexiform neurofibroma does not assure that one will not appear later in life. This is particularly true for plexiform neurofibromas which are located deep under the skin, which may not be apparent until after they have grown.

Although they do not occur frequently, there are two types of bone deformity which are typical for NF1, and these occur at birth when they occur at all. One involves the long bones, most commonly the shin bone (tibia). Infants affected tend to have a bowing or curvature of the lower leg. Some degree of curvature is normal, but an excessive degree indicates the possibility of this problem, which is referred to as tibial dysplasia. If tibial dysplasia is suspected, an X-ray is usually performed. If it is found, the child should be referred to an orthopaedist. The abnormal region of the tibia is very prone to fracture, and the fractures tend not to heal well. Orthopaedic care is usually directed towards prevention of fracture, or management of fractures if they occur.

The other typical bone deformity is abnormality of the bony wall behind the eye, called the orbit. Some newborns with NF1 have a defect of the bone behind the orbit, the sphenoid. This is often associated with bulging or recessing of the eye, and sometimes downward displacement of the eye. In addition, there may be plexiform neurofibroma within the orbit and enlargement of the upper eyelid. This can be disfiguring, and often tends to grow over the years. The abnormality of the sphenoid bone is detected by X-ray or CT scanning. It is not usually necessary to do anything about the absence of the sphenoid bone. The cosmetic problem associated with orbital dysplasia is to some extent amenable to correction by plastic surgery. Fortunately, this problem is relatively rare, and generally some signs are visible during the first year of life. Other than the bony deformities noted above, neurofibromatosis is not usually associated with congenital malformations. The heart and major organs are usually not involved.

Cafe-au-lait spots are usually clearly visible by the first year of life. Plexiform neurofibromas may grow, or may be noticed for the first time at this point. Sometimes a few freckles may be seen in the armpits or groins, and a few small neurofibromas may be noticed on the skin. The neurofibromas usually appear as small bumps on the skin, which are soft to the touch and have a pink or purple hue. They are not painful and rarely cause problems other than cosmetic. Young children usually do not have more than one or two small neurofibromas, and may have none.

Some children, however, develop multiple neurofibromas early in life. Such children do not necessarily develop additional severe complications of NF1 during childhood. Two abnormalities of growth are commonly noticed in preschool children.

One is short stature. Children with NF1 are often shorter than would be expected from the size of others in their family. The cause of this short stature is not known; medical testing is rarely productive, except in cases where growth rate suddenly and unexpectedly changes.

The other abnormality of growth is increased size of the head. This generally does not cause discomfort to the child, and is usually not correlated with neurological problems. The head grows at a faster rate than normal, but at a steady, consistent rate. As long as this is the case, it is usually not necessary to do an examination such as a CT scan. In rare instances, the head growth may be associated with symptoms such as vomiting or headache. In such cases, a CT or MRI scan is usually done to be sure that increased pressure of fluid inside the brain (hydrocephalus) has not developed.

Brain tumours can occur at any point in life, including early childhood. Fortunately, they are not common. One form of tumour which is particularly associated with early childhood is the optic glioma. This is a tumour of the nerve to the eye, the optic nerve. When it occurs in a symptomatic form, it may cause loss of vision, pain, bulging of the eye, or affect pituitary hormone secretion. Such symptomatic optic gliomas are diagnosed by CT or MRI scanning and can be treated, usually by chemotherapy. Radiotherapy is usually avoided due to its side effects. It is not uncommon to find evidence by CT or MRI scan of thickening of the optic nerve in children with NF1 who manifest no signs or symptoms of optic glioma. This may represent an abnormality of the development of the optic nerve in some children with NF1. Only rarely do symptoms of progression occur requiring treatment. It is recommended that all children with NF1 have ophthalmologic exams, done at least annually, to insure early diagnosis of symptoms of optic glioma.

Any of the features of NF1 mentioned above may begin to appear or continue to appear through school age. Thus, skin-fold freckles may increase, iris Lisch nodules may appear, plexiform neurofibromas may grow, and neurofibromas may become visible on the skin.

It is not unusual to become aware of learning difficulties in the school aged child with NF1, The exact frequency of learning disabilities in children with NF1 is not known, but estimates run as high as 25-50%, making this one of the most common  problems related to neurofibromatosis. The exact form of learning disability and degree of severity varies from child to child. Some experience difficulty with visual and spatial skills, some with speech and language, some with reading or math, or any combination of these ski Ms. In addition some have difficulty in focusing attention, although true hyperactivity does not appear to be especially common in children with NF1.

The cause of learning disabilities in children with NF1 is not understood, although it is believed that the NF gene mutation may somehow affect the development of the brain. It is rare for the learning disability to be associated with an abnormality on neurological exam or with a specific visible abnormality in the nervous system. The learning disorder is not progressive; that is, it generally does not get worse with time. The management of learning disabilities in children with NF1 is the same as for any child with a learning problem. A thorough assessment of the child's skills and areas of weakness should be undertaken, and an educational program designed to meet the child's special needs. This is generally done along with the school system. It is important to be aware of the possibility of learning disorders, since if these go undiagnosed a child can experience demoralizing failure at school instead of receive the special help he or she needs.

Adolescence is generally a time of change, and often this includes a change in the manifestations of neurofibromatosis. Individuals who have not developed neurofibromas during childhood often begin to see skin neurofibromas during puberty.

Pre-existing plexiform neurofibromas often grow at this time. Skin freckling may also increase. The cause of these changes is not well understood, but it is believed that changes in hormones may be responsible.

Similar appearance or growth of neurofibromas is also seen in many women with NF1 during pregnancy. This has raised the question of whether oral contraceptives should be avoided by women with NF1. In fact there is no clear evidence that oral contraceptives can be responsible for progression of neurofibromas, although the issue has not been carefully studied.

Adulthood

It is impossible to predict the course of NF1 in anyone with the disorder. Manifestations of neurofibromatosis generally do not disappear once they develop, although cafe-au-lait spots sometimes fade in later life.

Neurofibromas can appear at any time, as can symptoms of nerve compression. Although bone deformities are generally present from birth, cosmetic impairment from a neurofibroma can develop at any time in life. Learning disabilities do not disappear in adulthood, but adults with NF1 and learning disability can lead productive lives if their learning problems were recognized early and appropriate support provided.

As has been mentioned already, most individuals with NF1 live long and generally healthy lives. Yet it must be recognized that some complications of neurofibromatosis can be life-threatening. The most frightening to many people is cancer.

Neurofibromas are not cancerous growths; they do not spread through the body, even though they may appear in many places on the skin. In some persons, however, a cancer may develop within a neurofibroma. This does not usually happen to the small skin neurofibromas, but seems to be more likely to occur in the plexiform neurofibromas. The signs of malignancy would be the appearance of pain in a previously painless mass, and sudden growth, or the development of a focal neurological problem such as weakness. It is common for plexiform neurofibromas to be painful if bumped or otherwise traumatized, but this is different from the pain associated with malignancy. Pain indicative of cancer is more likely to occur spontaneously, without any evidence of injury to the mass. Likewise, not all growth indicates malignancy.

Neurofibromas commonly grow, especially the plexiform neurofibromas. Sudden growth of a portion of the neurofibroma is more indicative of malignancy than slow, steady growth of a larger mass. Malignancy related to neurofibromatosis is estimated to occur in about 5% of affected individuals. Although this might seem like a large number, it must be compared with the fact that 20-25% of all people—with or without neurofibromatosis—will develop a malignancy sometime in their lives. The malignancies related to neurofibromatosis can be treated, usually with a combination of surgery, radiation, and chemotherapy.

The outcome depends largely on how early the cancer is detected. In addition to malignancies, the possibility of tumours in the brain and spinal cord must be considered. These, too, occur in relatively few persons with NF1, although the risk to people with NF1 of developing a brain tumour is much higher than the risk to the general population. These are usually detected after symptoms such as headache, vomiting, seizures, visual disturbance, or behavioural change are detected. There may be an abnormality noted on neurological examination. The tumour would be diagnosed by CT or MRI scan. Sometimes the tumour will be biopsied, or even removed, by surgery. The treatment is usually radiation therapy, or, in some cases, chemotherapy.

It should be stressed that not all headaches in persons with neurofibromatosis mean that a brain tumour is present. Ordinary headaches, tension headaches and migraines, occur at least as commonly in persons with NF as in the general population. Persistent or especially severe headaches should be reported to a physician.

The child with NF1 should not be treated as ill, or as excessively fragile. There is no need to restrict activity, unless there is known to be a particular complication of neurofibromatosis, which would be prone to injury. It is also not necessary to carefully document every skin spot or bump. These will be noted by the child's physician during annual follow-up visits. The major things to be watching for are sudden changes in the size or appearance of a neurofibroma, unexplained pain, or, as noted above, persistent or severe headaches. Both the family and school teachers should be aware of the possibility of learning disabilities.

One of the most common and difficult questions asked by parents of children with NF1 is when and how to explain the disorder to the child. There is no single correct approach to this. Much depends on the adjustment of the parents, the maturity of the child, and the specific manifestations of neurofibromatosis present in the child. Ultimately, though, every child with NF1 will begin to question why he or she must go to a special doctor, or why he or she looks different from other children.

If any general advice can be given here, it is to answer the child's questions honestly, giving as much information as the child seems to be able to understand. One need not go into great detail about possible complications of neurofibromatosis with a young child, but evasive answers often provoke fear rather than provide reassurance, and false answers may impair later trust. Moreover, sooner or later the child will learn about neurofibromatosis, if not from his or her parents, then from friends or articles in magazines or newspapers. This can lead to misinformation and consequent fear well out of proportion with the risks associated with the disorder.

If the parents and physicians serve as the main source of information about neurofibromatosis, one can be more certain that the information is accurate and balanced.

Parents often ask whether the school system or teachers should be informed that their child has—or may have—neurofibromatosis. The concern is often raised that this might result in the child being labelled as "learning disabled", setting up a self-fulfilling prophesy. Actually, it is common for more harm to be done by not informing the school teachers, and having them fail to recognize learning disabilities, and mislabelling a child as a "behaviour problem". A frank discussion with a child's teachers can often correct common misconceptions about neurofibromatosis, and lead to earlier detection and treatment of learning problems related to the disorder. A good general rule is is to talk with the teachers and with the school if you can see that such a discussion may be of benefit to your child's school experience.

Many children diagnosed as having neurofibromatosis appear to be the only members of their families to have the condition. Neither parent may seem to be affected, and no relative is known to have had the condition. There are two possible explanations for this situation.

One is that one of the parents actually does have neurofibromatosis, only its manifestations are so mild that he or she may be unaware of being affected. Alternatively, the genetic change, or mutation, that caused neurofibromatosis may have first arisen in the sperm or egg cell that produced the child. In this case, neither parent will be affected. Deciding between these alternatives can be important. In the first case, where one parent is affected, the risk of reoccurrence of NF1 in future offspring is 50%. In the latter case, where the child is affected due to new mutation of the NF gene, the risk to future offspring of the parents will be very low, practically the population risk.

At present, the best way to resolve the issue is to thoroughly examine each parent, generally with a skin examination and eye examination looking for Lisch nodules. If neither parent is found to have signs of neurofibromatosis the child is most likely a new mutation. It is not impossible for the parents to have other affected children, but it is unlikely. Similarly, if neither parent is affected, it is unlikely that brothers or sisters of the affected child will be affected, although they should be examined for signs of neurofibromatosis to be sure.

Regardless of whether a person with NF1 is the first one in the family to be affected or whether the condition has been present for many generations, all persons with NF1 have a 50% risk of transmitting the condition to any child. There is no way to predict the degree of severity of the condition in offspring: severely affected parents may have mildly affected children and vice versa. Genetic testing ("DNA testing") is currently being developed which, in some cases, may permit prenatal diagnosis. A physician or genetic counsellor can provide additional information about the availability of such testing. If it is decided that a child has NF1 on the basis of new mutation of the gene, it is natural to ask, "How did this happen?"

Parents often wonder if there is something they did which caused the mutation, such as exposure to radiation, medications, alcohol, etc. In fact, the cause of mutations in the NF1 gene is unknown. No environmental exposure has yet been implicated as a cause. In fact, genetic mutations occur commonly. Whenever a cell divides, an enormous volume of genetic information must be copied faithfully. It is not unusual for a bit of information to be copied incorrectly, resulting in mutations. Such random errors may well be the "cause" of mutations leading to neurofibromatosis, although further study of the NF1 gene will be necessary to be sure.

Mastery of the medical facts about neurofibromatosis may be the first step towards adjustment to living with the disorder. This cannot relieve uncertainty, but ignorance about the condition often produces a picture, which is worse than reality. It is therefore important to maintain open communications with health professionals who are involved in caring for a child with neurofibromatosis. Family and friends can likewise be a source of support. Sharing accurate information with them can prevent them from satisfying their curiosity with inaccurate accounts in the lay press. Many seek professional guidance from clergy or counsellors. Finally, there is the resource of other families with neurofibromatosis, who can share experiences, concerns, and advice.

Reviewed and edited by Professor Kathryn North, April 2008