Dr. Kevin Yip

Dr Kevin Yip
Orthopaedic Surgeon
MBBS(UK), FRCS(EDIN), FAM(SING), FHKCOS(ORTHO)

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Neurofibromatosis

Basics
Description
  • 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
Epidemiology
Incidence
  • ~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.
 
Genetics
  • Inherited in an autosomal-dominant pattern
  • Presents in ~1/2 of the patients as new mutations
  • Thought to occur with complete penetrance
Etiology
  • 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.
Diagnosis
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.
Tests
Lab
No laboratory tests reveal abnormalities specific for NF.
 
Imaging
  • 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.
Treatment
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.
Activity
  • Bracing for prepseudarthrosis of the tibia, especially during activities, is recommended.
  • Otherwise, activity should not be restricted unnecessarily.
Medication
Although speculative, angiogenesis inhibitors may be used to decrease the vascularity of plexiform neurofibromas and allow easier surgical removal.
 
Surgery
  • 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.
Follow-up
Prognosis
Life expectancy may be compromised by severe mental retardation and malignant disease.
 
Complications
  • 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.
Miscellaneous
Codes
ICD9-CM
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.
FAQ
Q: Should soft-tissue neurofibromas be removed?
A: Only if they are growing excessively or are causing symptoms.

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