Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities, and attention deficits; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs (pseudoarthrosis), and improper development of certain bones.Associated symptoms and findings may vary greatly in range and severity from person to person, even within the same family.
Often the first sign of NF1 is the appearance of multiple brown spots on the skin (café-au-lait macules) or freckling in the underarm (axillary) or groin (inguinal) regions, which may occur as early as birth or infancy.
Lisch nodules may also be present early in life, and are highly suggestive of an NF1 diagnosis, as they occur in approximately 97% of affected individuals.
More rarely, affected individuals may develop certain malignant (cancerous) tumors.
NF1 may also be characterized by an unusually large head size (macrocephaly) and relatively short stature.
Additionally, disorders of bone density (osteopenia and osteoporosis) are more common in people with NF1 than in the general population.
The process by which these conditions develop is not fully understood, but has been associated with decreased activated vitamin D levels, increased parathyroid hormone levels, and increased markers of bone breakdown.
In 8-15% of affected individuals, neurofibromas may transform to become cancerous (malignant peripheral nerve sheath tumors), which are associated with pain, weight loss, night sweats, and require urgent evaluation and treatment.
Approximately 15% of people with NF1 develop brain tumors (gliomas), which nearly always develop during childhood.
The total number of neurofibromas in an adult may range from a few to hundreds or even thousands, and the number of these tumors tends to increase with age.
Pain may occur from an affected peripheral nerve, or as a result of regional mass effect on adjacent structures.
Such individuals do not inherit NF1 from their parents, but rather they are the first in their family with the disorder.