1.13 Neuromuscular and skeletal manifestations of neurofibromatosis

Neurofibromatosis type 1 (NF-1) is one of the commonest single gene disorders (17q11.2) (1 in 3000–4000 live births). The gene product functions as an antitumour agent, a function suppressed in mutations. At least 40% of children with NF-1 have serious cosmetic or functional involvement of the musculoskeletal system. NF type 2 is particularly associated with acoustic neuromas (22q12.2), is much rarer (1 in 25 000), and has few, if any, musculoskeletal manifestations.

NF-1 presents to orthopaedic surgeons with spinal deformity; neurofibromas, and other tumours affecting the spinal cord and peripheral nerves; pseudarthrosis of long bones, especially the tibia; limb gigantism associated with plexiform neurofibromas; and pectus excavatum. Radiological manifestations of NF-1 frequently cause diagnostic difficulties, and may mimic other conditions. A rare but important association is with phaeochromocytoma, which should be considered before anaesthetizing anyone with NF-1.

Consider NF when confronted by:

Check for a family history of NF-1. Look for cafe-au-lait spots. (The skeletal manifestations of the disease may precede the appearance of neurofibromas). There should be more than 6 spots with a diameter greater than15mm in children older than 5 years. Freckles appear in the axillae and groin later in childhood. Lisch nodules in the iris are diagnostic. These can only be seen with a slit lamp. Subcutaneous and nerve-based neurofibromas are common. There is an increased risk of developing brain tumours (especially optic glioma) and leukemia. Learning disability is common. About 2% of individuals with NF-1 also develop phaeochromocytoma. This should always be suspected in patients who are hypertensive.

Pseudoarthrosis appearing in any long bone in infancy is usually, but not always, associated with NF-1 (50–90%). The tibia is by far the most frequent (1 in 250 000 live births), but pseudoarthrosis has been observed in all of the other long bones. This is a very difficult condition to manage and beyond the scope of this text. At least six different patterns have been described (Boyd classification). Surgical treatments include: osteotomy; onlay grafts; bypass grafts; pedicle grafts; intramedullary rods; vascularized bone graft; electrical stimulation; bone transport; amputation, either as a primary procedure or as salvage.

Hypertrophy of a bone, digit, or an entire limb, combined with unusual lengthening or shortening of a bone can give serious cosmetic and practical problems. These require plastic and orthopaedic surgical expertise.

Spinal deformity occurs in about 5% of cases. Scoliosis may be indistinguishable from idiopathic scoliosis, or be dysplastic with short segment aggressive deformities with loss of part or all of the vertebral body that require surgical treatment. Kyphosis is commonly associated with dysplastic spines. This may present challenging problems for the surgeon, though not usually sufficient to damage the spinal cord unless there is dislocation of the spine or a large meningocoele. It is best to avoid resection of tumours associated with dysplastic curves. Other features are scalloping of the posterior margin of vertebral bodies; enlargement of the intervertebral foramina; pedicle defects; vertebral body dysplasia; dumb-bell tumours; dural ectasia (a saccular dilatation of the dura, sometimes with extensive protrusion of the dura out of the intervertebral foramen); lateral meningocele; and, rarely, intrathoracic meningoceles. Spinal tumours, both intra- and extradural are common and include neurofibromas, gliomas, meningiomas and schwannomas.

These are extensive tumours involving muscle and bone especially in the pelvis and lower limbs. They are difficult or impossible to resect. Many remain stable, but may become malignant. Magnetic resonance can be used to monitor size and shape. Positron emission tomography scanning seems a good method for identifying malignant change.

NF-1 patients have a high frequency of skeletal involvement, sphenoid dysplasia is diagnostic. Bone deformities are caused by destruction by neurofibromatous tissue, aberrations of skeletal growth, abnormal development of body parts or systems, malignant bone tumours, intervertebral foramenal enlargement, cortical bone defects, bone cyst formation, bowing of long bones, and pseudoarthrosis of long bones.

This is focused on the management of complications. This can be complex and challenging. Resection of individual tumors should be confined to those that are symptomatic.