Vascular anomalies are often seen and those that impact blood supply to the kidneys can induce severe hypertension especially in children (pheochromocytomas are also a risk). Coarctations and aneurysmal anomalies can obstruct the blood supply to major organs, sometimes acutely. Some degree of cognitive impairment and sometimes mental retardation can be seen in nearly half of patients, even in the absence of other obvious neurological deficits. Short stature, tibial pseudoarthrosis, sphenoid dysplasia, and scoliosis are common. Osteopenia and frank osteoporosis are seen in approximately half of patients. A small percentage of patients develop malignant peripheral nerve sheath tumors (lifetime risk 8-13%). Rare patients develop other malignancies, primarily sarcomas.
Diagnosis is based on the presence of some combination of typical features such as cafe-au-lait spots, Lisch nodules, neurofibromas, optic pathway gliomas, axillary or groin freckling, and bone dysplasia. The underlying disease is progressive and the accuracy of diagnosis improves in older patients.