I have a question about my son's health and segmental NF. During a routine annual physical exam, at the age of 8 yrs. old, I questioned my son's pediatrician about the noticeable freckles in my son's armpits and on the left side of his neck (which only became noticeable within that year). She referred us to a pediatric dermatologist, concerned that it was neurofibromatosis. The dermatologist immediately responded that he doesn't have NF, because he does not have cafe au lait spots to fit the size and number criteria; he is advanced academically, and has no hearing problems. Then the dermatologist backpedaled and stated that perhaps we should see a geneticist because there is such a thing as "segmental NF". My son is 14 years old now, in the throes of puberty (which I've read is the developmental stage when manifestations most often occur), without noticeable tumors, very athletic, and very strong academically. Is it wise to seek the advice of a geneticist for a "diagnosis" or not? Is there still only palliative treatment for confirmed cases of NF?
-A curious adult from Indiana I can understand your concern...a genetic disease diagnosis can be a scary thing, especially for your kids. If your son does have segmental NF (more about that later), it would be useful for him to know this for when he wants to have children. Fortunately, segmental NF is usually not dangerous in itself. But, there is a chance that your son could pass the more serious, full NF, down to his kids. Neurofibromatosis (NF) is a common genetic disease affecting the skin and nervous system. Minor symptoms are freckles and larger dark patches on the skin (cafe au lait spots). More serious effects are learning and behavior problems, and increased rates of brain and nerve tumors. How is NF treated? Treatment is aimed at reducing or stopping growth of tumors as they arise. This means surgery to remove the tumor, or giving drugs that slow down tumor growth. In the future we may understand better how and why cancer occurs in NF and then more specific therapies can be developed. We may even be able to prevent tumors from forming in the first place. No treatment is necessary for minor skin symptoms. NF is dominantly inherited, so only one bad copy of the gene is enough to cause the disease. In other words, if you have full NF, you have at least a 50% chance of passing it down to your kids. Since you didn't mention it, I presume neither you nor your spouse has NF. If this is the case, where did it come from? NF comes from mutations in the huge neurofibromin gene. Errors in this very large gene happen more often than in other genes because there are so many more chances for a mistake to occur. Think of it this way -- let's say there is a 1 in a million chance of having a change in your DNA. If one gene is 1 million base pairs long and another is 1000, which gene is more likely to get a change? That's right, the million base pair gene. Just like our hypothetical million base pair gene, the neurofibromin gene is so big that it has a good chance of picking up a DNA change or mutation. About one half of the people seen by doctors with NF have mutations that are new, not passed down from their parents. Now segmental NF happens when the disease affects only a small area of the body. It is due to a mistake in the neurofibromin gene being present in only some of a person's cells, while other cells are perfectly normal. How does this mild form of NF occur? Remember, we all start out as a single cell that divides and divides until we get to our 50-100 trillion cells. With each cell division, the DNA in the cell is copied so that the new cells all receive the same DNA. However, there is a small chance that a DNA change can happen in one cell. If it happens early enough, then a good chunk of a person will have this mutation. This is called mosaicism -- the person is made up of a mosaic of cells. In fact, it is likely that everyone contains a few cells with mistakes in their DNA from an error during development. But don't worry! The small number of cells involved and their location make these changes completely without effect. For example, a skin cell with a mutation in a gene for making a muscle protein does perfectly well, because that gene is not needed in skin. However, there can be a problem if a large number of a person's cells have a bad copy of a gene. For example, if there is a mistake in an important protein like neurofibromin, the person can show signs of NF. These signs will be found in the region of the body where those cells with changed DNA are located. If a mutation occurs very early and most of a person's cells have the DNA mistake, then their disease could be serious. If some of the cells with the changed DNA are sperm or egg cells, then that mutated gene could be passed down to that person's children. In that case, all the cells of that child will have the bad copy of neurofibromin and they will have the full NF disease. So you see, while genetic diseases are passed down from parent to child, they have to start somewhere. The first person to have a disease-causing mutation is sometimes a mosaic -- a mixture of cells with both normal and changed forms of the gene. Their disease is usually mild. Still, its good to know if there is a DNA change when starting a family.

A nerve cell

DNA replication can cause mutations