NF-I presents with café-au-lait spots, multiple cutaneous or subcutaneous
neurofibromas, or iris Lisch nodules, which are rare in children younger
than 3 years. Nodular plexiform neurofibromas are similar to subcutaneous
neurofibromas but involve nerve plexuses or dorsal nerve roots; they may
grow in the mediastinum. Diffuse plexiform neurofibromas involve all skin
levels and are usually hyperpigmented. Neurofibromas may appear anywhere and
grow with age. They all carry a risk of functional or anatomical
complication by compression or invasion. Other common findings are the
following. Skeletal anomalies: Sphenoid wing dysplasia, early-onset and rapidly progressive
thoracic scoliosis (in 10%) with kyphosis; patients with kyphoscoliosis
are at high risk for cervical vertebral anomalies (e.g., dysplasia with or
without paraspinal neurofibromas), which can be asymptomatic. Vascular Anomalies: Systemic
hypertension is very frequent and caused by renal artery stenosis,
pheochromocytoma, or catecholamine-secreting nodular plexiform
neurofibromas. Pheochromocytoma: 5% of patients. Optic Gliomas: In 15% of patients with NF-I but only
one third become symptomatic and require treatment. Seizures: Usually caused by a
brain tumor or hydrocephalus, but no anatomical cause is found in 6% of
patients. Learning disabilities caused by developmental delay: motor problems, hypotonia.
Pseudarthrosis (usually of the tibia) or pathologic limb fracture in 2% of patients with
NF-I. Congenital glaucoma is present in 0.5% of neonates with NF-I. Increased risk of developing certain
types of malignancy: juvenile chronic myelogenous leukemia, Wilms tumor,
rhabdomyosarcoma. Short stature. Enlarged spinal canal on CT scans is not uncommon with or
without diastematomyelia. Secondary involvement of the spinal cord occurs in
a variety of ways: compression by adjacent neurofibromas, vertebral collapse
from neurofibroma-associated erosions, and compression from severe untreated
kyphoscoliosis. Neurofibrosarcomas can occur anywhere; already established
neurofibromas develop, probably most often in the large plexiform variety.
Visceral nerves are also involved, and the large bowel may demonstrate a
nonneurofibroma hyperganglionosis that is functionally similar to
Hirschsprung disease.