Neurofibromatosis Type 1 (NF1)
More common than cystic fibrosis and hereditary muscular dystrophy combined, Neurofibromatosis Type 1 (NF1) occurs in approximately one out of every 3,000 births. NF1 has also been referred to as peripheral neurofibromatosis or von Recklinghausen disease. It differs clinically from another type of neurofibromatosis, called NF2. Individuals with NF1 will not develop NF2, nor will they pass NF2 onto their children.
Common features of NF1
NF1 is a very unpredictable disorder. It varies widely in severity from one person to the next, even between two people in the same family. Some people with NF1 go through life with only a few café-au-lait spots or neurofibromas, while others may have major cosmetic or medical problems due to NF1.
Such uncertainty may make it very difficult to know what to expect for a child with only café-au-lait spots. In this respect, there is no way to predict the severity of NF1. Severely affected parents may have mildly affected children and mildly affected parents may have severely affected children.
Despite the unpredictable nature of NF1, some common features of this genetic disorder include
- Skin, bone and eye abnormalities: pigmentary abnormalities (particularly café-au-lait spots), skinfold freckling, scoliosis, bone deformities, Lisch nodules
- Nerve tumors: nerve tumors, weakness, pain
- Optic nerve and other brain tumors: brain tumors, vision loss, seizures, paralysis, headaches
- Learning and attention deficits: learning disabilities, poor school performance, hyperactivity/attention deficit
- Heart defects: valve defects, abnormalities of the arteries
Diagnosis of NF1
A diagnosis of NF1 is made when an individual has two or more of the following findings:
- At least six café-au-lait macules over 5 mm in greatest diameter before puberty, or six café-au-lait macules over 15 mm in greatest diameter after puberty
- Two or more neurofibromas of any type or one plexiform neurofibroma
- Multiple freckles in the axillary (armpit) or inguinal (groin) regions
- A distinctive bone abnormality involving the eye socket or arm/leg bones
- A tumor on the optic nerve located in the brain called an optic glioma
- Two or more Lisch nodules on slit-lamp examination
- A parent, sibling, or child with NF1
Genetics of NF1
NF1 is a hereditary or genetic disorder, due to an alteration (mutation) in the NF1 gene. All people have two copies of the NF1 gene, one they get from their mother and one they get from their father. When one copy of the NF1 gene is altered, it is no longer able to work properly and this results in NF1.
Children with NF1 may either inherit NF1 from a parent with NF1 or they may be the first person in their family to be diagnosed with NF1. Half of all children with NF1 inherit an altered NF1 gene from a parent who has NF1. There are times when a parent is so mildly affected that they may never have been diagnosed with NF1. When neither parent is known to have NF1, it is important that each parent be thoroughly examined by a physician familiar with NF1, to determine whether either of the parents has NF1.
The other half of children with NF1 are the first person in their family to be affected. In this case, neither parent has NF1. The genetic change that causes NF1 in these children is a new alteration in the NF1 gene that likely arose in the sperm or egg cell that produced the child. This change is not caused by anything either parent may have done or not done before, during or after pregnancy. When neither parent has NF1, the chance of having another child with NF1 is very low.
If a parent has NF1, the chance of having another child with NF1 is 50-50 for each and every future pregnancy. 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% chance of having a child with NF1 for each and every future pregnancy.
Genetic or DNA testing for NF1 is currently available. A physician or genetic counselor can provide additional information about the availability of such testing.