Featured on Channel NewsAsia


  • Most common single gene disorder in humans
  • The disease involves multiple organ systems; the skeletal and nervous systems account for the greatest number of clinical features.
  • The most common form is NF1 (addressed here); NF2 refers to bilateral acoustic neuromas.
  • The manifestations of NF1 may not develop until late childhood.
    • Some signs may be present at birth, but neurofibromas may take years to become apparent, and diagnosis usually is made in later childhood.
  • Synonym: von Recklinghausen disease
  • ~1 in 3,000 newborns
  • Males and females are affected equally
Risk Factors
Advanced paternal age has been associated with an increased incidence of NF.
  • Inherited in an autosomal-dominant pattern
  • Presents in ~1/2 of the patients as new mutations
  • Thought to occur with complete penetrance
  • Genetic disorder
  • Secondary to a defect in the protein neurofibromin
Associated Conditions
  • Nearly 50% of people have cognitive delays ranging from severe retardation to slight learning disabilities.
  • A few patients develop metabolic bone disease that results in a type of osteomalacia.
  • Hypertension on the basis of renal artery stenosis or pheochromocytoma may be found.
Signs and Symptoms
  • To establish the diagnosis, 2 of the following National Institutes of Health diagnostic criteria must be met:
    • 6 cafe-au-lait spots measuring >5 mm in children and >15 mm in adults
    • 1 optic glioma
    • >2 Lisch nodules on the iris
    • 1 osseous lesion typically seen in NF, including vertebral scalloping, dystrophic scoliosis, rib penciling, or pseudarthrosis of a long bone
    • A 1st-degree relative with the disease
    • Axillary or inguinal freckling
    • Cutaneous or plexiform neurofibromas
  • Symptoms vary, depending on the criteria:
    • Plexiform neurofibromas often are associated with pain and neurologic deficit in the distribution of the particular nerve.
    • Cutaneous neurofibromas usually cause few symptoms.
Physical Exam
  • Examine the neck and spine for deformity.
  • Inspect all the skin, including the axillae.
  • Ophthalmologic referral should be made so that the eyes can be examined with a slit lamp for Lisch nodules and optic glioma.
  • Limb lengths should be measured and checked for angulation.
No laboratory tests reveal abnormalities specific for NF.
  • The skeletal manifestations usually can be identified on plain radiographs:
    • May show posterior vertebral body scalloping
    • The dystrophic type of scoliosis is characterized by penciling of the ribs, severe apical rotation, short, segmented curves, and malformed vertebrae.
    • The features of the pseudarthrosis that can occur in long bones can range from a cystic appearance to severely thinned and pointed pseudarthrosis, which fractures at birth.
    • Sclerosis and constriction also can be found at the pseudarthrosis site.
    • Dural ectasia and pseudomeningocele also can affect the spine.
  • When instrumentation is planned to correct a spinal deformity, MRI should be obtained to evaluate the spinal canal for these changes.
  • CT scanning may be helpful in assessing the laminae and pedicles for fixation.
  • Characteristic long-bone lesions can include anything from benign scalloping of cortices to permeative lesions that resemble malignant disease radiographically.
Pathological Findings
  • The disorder is 1 of cells of neural crest origin: The cells of the embryonic neural crest are destined to form tissue in many different organ systems, accounting for the diverse manifestations of the disease.
  • Lisch nodules of the iris are hamartomatous deposits.
  • The bone in pseudarthrosis typically is fibrotic, with few osteoblasts.
  • Cutaneous neurofibromas are composed of Schwann cells and connective tissue.
Differential Diagnosis
  • Proteus syndrome most closely resembles NF in its manifestations.
  • Patients with isolated congenital pseudarthrosis of the tibia must be monitored for NF because the cafe-au-lait spots may develop later NF.
  • NF2 consists of only bilateral acoustic neuromas.
General Measures
  • Patients should be seen regularly by a geneticist or primary physician to rule out developmental delay, growth disturbance, scoliosis, or neurologic deterioration.
  • Patients usually are functional, except those who are severely mentally handicapped.
  • No specific dietary requirements exist.
  • Bracing for prepseudarthrosis of the tibia, especially during activities, is recommended.
  • Otherwise, activity should not be restricted unnecessarily.
Although speculative, angiogenesis inhibitors may be used to decrease the vascularity of plexiform neurofibromas and allow easier surgical removal.
  • Dystrophic scoliosis should be treated surgically if any evidence of progression is seen.
  • Anterior and posterior fusions usually are recommended if focal kyphosis or a curve >50-60° is present in a skeletally immature patient.
  • When diagnosed, patients with dystrophic tibial changes should be braced, and the bracing should be continued until skeletal maturity.
  • If fracture occurs, use intramedullary nails (with bone grafting or vascularized fibula bone grafting) or compression and distraction (Ilizarov) treatment with ring fixators.
    • All treatment should be protected after union occurs until the end of growth.
  • Plexiform neurofibromas should not be treated surgically because total removal is nearly impossible and neurologic deficits typically occur.
  • Leg-length inequality should be charted and followed with serial scanograms to ascertain the timing of contralateral leg epiphysiodesis or limb lengthening.
Life expectancy may be compromised by severe mental retardation and malignant disease.
  • Patients with NF1 have a high incidence of malignancy.
  • Usually, these tumors are of the central nervous system.
  • Plexiform neurofibromas also can degenerate into neurofibrosarcomas.
  • Amputation of a leg may be necessary in a patient with severe pseudarthrosis because correction of the nonunion is not always successful.
  • In rare instances, the function of the patient may be best served with amputation.
  • Some patients with dystrophic scoliosis have malformed vertebrae.
  • If substantial kyphosis exists, correction can cause neurologic compromise.
  • Spinal cord monitoring should be performed during all spinal procedures.
Patient Monitoring
  • Annual scanograms are indicated for limb-length discrepancy.
  • Physical examinations for detection of scoliosis should be performed on a yearly basis while the child is growing.
  • Hypertension is a common finding in patients with NF and should be monitored regularly.
237.7 Neurofibromatosis
Patient Teaching
  • The incidence of tumors (especially those of the nervous system), including optic gliomas, astrocytomas, and acoustic neuromas, is increased.
    • Education about the early signs of auditory, visual, or motor disturbances should be discussed with patients.
  • Educate the patient regarding the need to protect against pseudarthrosis of the tibia until skeletal maturity.
  • Discuss the potential for limb-length discrepancy when pseudarthrosis of the lower extremity or limb gigantism is present.
    • Typical discrepancy in both disorders rarely exceeds 6 cm.
  • If possible, bracing of pseudarthrosis in the tibia should be attempted.
  • Bracing for dystrophic scoliosis is not effective.
  • Bracing for the more commonly encountered idiopathic type of scoliosis should be instituted when the regular indications for idiopathic scoliosis are met.
Q: Should soft-tissue neurofibromas be removed?
A: Only if they are growing excessively or are causing symptoms.

Comments are closed.