The clinical features of NF1 are often not present at birth or in early childhood and the diagnosis is made based on the history of the affected parent or sibling. In most cases, a child who is born to a family with NF1 and does not present with any clinical features by age 10, will most likely be unaffected by the disorder . The presentation of a patient with NF1 is quite variable. In children, the most frequent initial finding is presence of multiple café-au-lait spots. These skin lesions may be present at birth and become more obvious with time. In most infants, the café-au-lait spots do increase in size and number with advancing age.
Freckles in the inguinal or axillary region are very rarely seen at birth. However, as the child gets older and passes puberty, these skin lesions become more obvious. The neurofibromas are rarely seen in infants and young children. These lesions tend to occur past the age of puberty and become prominent by the adolescent years. The skin lesions initially start off as papules on the face, scalp, extremities and scalp. Some individuals may only have deeper neurofibromas that may only be felt via palpation. Some neurofibromas may not only be deep but also be locally invasive and produce pain with even mild palpation. The skin lesions often show rapid growth just after puberty or during pregnancy. Plexiform neurofibromas may also be associated with excess hair growth and darkening of skin. The growth of these neurofibromas can be rapid and that may be indicative of a malignant lesion.
The optic nerve gliomas are usually low grade and occur in 1/5th of patients with NF1. These lesions are often silent but can present with symptoms in young children. Females are more likely to develop visual problems compared to males. Besides vision loss, others may develop peripheral visual field deficits, proptosis and difficulty discriminating color. The visual loss is often unilateral and often not correctable. Rarely a neurofibroma may encroach on nerve pathways of the hypothalamus-pituitary axis and present as precocious puberty in children.
The Lisch nodules are usually not visible to the naked eye and require a slit lamp exam or use of an ophthalmoscope. Fundoscopic exam may reveal choroidal abnormalities. A variety of musculoskeletal defects may be seen in NF1 include bowing of the tibia/ulna, angulation and bowing of the long bones. Bony dysplasia of the sphenoid bone may be obvious but is often asymptomatic. Scoliosis may first become obvious in childhood and may be associated with kyphosis. Most individuals do not have progression of scoliosis but when it does progress it can be deforming and requires surgical intervention.
At every visit, the blood pressure must be measured because of the possibility of primary hypertension or developing secondary hypertension from a pheochromocytoma or renal artery stenosis. In all children with NF1, head circumference needs to be monitored for the first few years of life. Head enlargement may occur rapidly and may be appear abnormal. Most individuals with NF1 tend to have short stature.
The initial clue to the presence of NF1 is made from a clinical exam. Over the years, criteria have been established to help clinicians make an early diagnosis of NF1 . The reason for the criteria is that not all clinical features appear until adolescence and often the diagnosis is delayed. For clinical diagnosis, there must be at least two of the seven criteria listed below.
However, in young children without clinical features, molecular testing may be of help. Today the NF1 gene can be tracked though linkage analysis and any mutation can be detected during the prenatal period via chorionic villus sampling or amniocentesis. Urinary levels of epinephrine and norepinephrine are measured if there is suspicion of a pheochromocytoma.
Plain X-rays are used to detect musculoskeletal abnormalities. CT scans and MRI are also used to image the brain to detect optic gliomas, presence of hydrocephalus, spinal cord lesions, acoustic neuromas and pheochromocytomas .
Neurofibromatosis has no cure. The majority of patients are monitored for life for development of complications resulting from the disease . Patients need to be examined every 6-12 months for the following clinical features:
At each visit the patient should be asked about any neurological symptoms like urinary or fecal incontinence, pain, tingling, weakness or paresthesia. Symptoms of spinal cord neurofibroma often develop slowly and are best treated when diagnosed early. Painful or ulcerated neurofibromas can be treated with chemotherapy and/or radiation. However, clinicians should try and avoid radiation therapy, as there is a potential for increased risk of secondary malignancies .
Sometimes for isolated neurofibroma that are ulcerated, causing pain or loss of function, surgery can be used to excise the lesions. Neurofibromas may compress important nerves and affect vision or may be growing rapidly and invading important structures. These lesions usually required emergency surgical therapy. Because of the need to excise large lesions, consultation with a plastic surgeon is recommended to cover the resulting wound. In some patients who develop sudden progression of scoliosis or other bony defects, an orthopedic consultation is required.
If pheochromocytoma is diagnosed, surgical excision is required. Some patients with hypertension due to renal artery stenosis may benefit from angioplasty or surgical repair of the renal artery lesion. Orthopedic intervention is indicated for rapidly progressive or severe bony defects. Laser is now used to treat the pigmented skin lesions but has not proven to be successful for café-au-lait spots.
Compared to the general population, the life expectancy of individuals with NF1 is slightly lower. Follow up studies show that on average NF1 individuals have 8-10 year decrease in their life span compared to the general population. However, it is important to know that patients with NF1 have a continuing risk of developing both malignant and benign tumors, which may occur on critical areas of the body and can severely impair function and quality of life  .
The precise cause of NF1 is not known but thought to be related to the protein molecule neurofibromin. Neurofibromin has many diverse functions and controls overgrowth of certain nerve and other cells. It appears that neurofibromin prevents uncontrolled growth of several cell types. When there is a decrease in neurofibromin, the clinical features of neurofibromatosis predominate.
The incidence of NF1 is about 3 in every 10,000 births. However, these numbers are underestimates because there are some individuals who have no symptoms or clinical features of the disorder and never come to medical attention. NF1 occurs with equal frequency in all races. Newer data indicates that the risk for developing optic glioma is slightly less in African Americans compared to Hispanics and Caucasians. However, optic gliomas are more likely to occur in females compared to males. Similarly, the degree of scoliosis is more severe in young females compared to males.
Neurofibromatosis is an inherited genetic disorder caused by a deletion or a mutation of the NF1 gene. The gene product of the NF1 gene known as neurofibromin, normally suppresses growth of nerve and many other related cells. When gene mutation occurs, there is uncontrolled overgrowth of certain nerve and other cells. Recent evidence indicates that the NF1 gene is localized the long arm of chromosome 17. Over the years, several hundred mutations of the gene have been identified in patients with NF1.
There is no way to prevent NF1 because it is a genetically inherited disorder. However, early detection during pregnancy can help determine if the infant has the disorder. Families with NF1 should be referred for genetic counseling.
Neurofibromatosis type 1 (NF1) is an autosomal dominant medical disorder that primarily affects the skin, bone and nerve tissues. The disorder often presents with freckles in the axilla, café-au-lait spots (milky white lesions), bone dysplasia and growth of benign and malignant nerve tumors known as neurofibromas. Many individuals also develop essential or secondary hypertension due to renal artery stenosis or pheochromocytomas. The neurofibromas are usually multiple and often occur in critical areas of the body, leading to nerve compression. The one major difference between NF1 and NF2 is the former has a lower incidence of brain tumors, whereas patients with NF2 have fewer skin lesions but have a higher frequency of brain lesions like meningiomas and bilateral acoustic neuromas.
Neurofibromatosis type 1 (NF1) is an inherited disorder that primarily affects the skin, bones and nerves. It is caused by a mutation of a gene on chromosome 17. The disorder is characterized by changes in skin coloring and the growth of tumors along nerves, brain, and in other body parts. When NF1 is diagnosed, the patient and the family should be referred to the national or local support group for both emotional support and continuous updates on the advances in treatment. Patients should be educated about possible symptoms that may require surgery. In addition, patients should be told about potential neurological symptoms that may indicate spinal cord compression. All patients and their families should be referred for genetic counseling should they desire to have children in future. Patients should be told to have continuous follow up with their healthcare provider and be cognizant of any new symptoms that may arise.