eMedicine Specialties > Orthopedic Surgery > Pediatrics

Neurofibromatosis

Author: Alvin H Crawford, MD, FACS, Professor of Pediatrics and Orthopedic Surgery, University of Cincinnati College of Medicine; Director, Division of Pediatric Orthopedic Surgery, Department of Orthopedic Surgery, Cincinnati Children's Hospital Medical Center
Contributor Information and Disclosures

Updated: Jan 15, 2009

Introduction

Type 1 neurofibromatosis is a multisystemic disease.¹ Neurofibromatosis type 1 (NF1), also called von Recklinghausen disease or peripheral neurofibromatosis, is an autosomal dominant disorder. The entity is common and affects 1 in 4000 individuals. It is one of the most common dominantly inherited gene disorders in humans.² The gene locus of neurofibromatosis in humans recently has been identified and cloned. It is characteristically localized to chromosome 17. Patients with NF1 develop Schwann cell tumors called neurofibromas and pigmentation abnormalities (see the diagnosis criteria in Clinical, below).

Tilesius von Tilenau first described neurofibromatosis in 1793, and R. W. Smith further described it in 1849. However, in 1882, von Recklinghausen was the first person to associate the origin of this disorder to tumors arising from cells of the nerve sheaths.³

Historically, neurofibromatosis is well known because of "the elephant man," Joseph Carey Merrick, who was a medical curiosity in London in the 1880s. His disfiguring deformity of the head and extremity involvement and his vertebral deformities made him famous, and these deformities were described later in a play, a film, and several books. More recently, Tibbles and Cohen have considered that Merrick had Proteus syndrome rather than neurofibromatosis;⁴ however, the association of the elephant man with NF1 brought the condition needed attention.

The orthopedic manifestations and, especially, the complications after treatment are common and have a prominent place in the orthopedic literature. The intent of this article is to identify the complications most commonly associated with the orthopedic manifestations of neurofibromatosis and to present strategies for their management.^5,6,7

For further information, see eMedicine articles on neurofibromatosis in dermatology, neurology, ophthalmology, orthopedic surgery, pediatrics, and radiology.

Related eMedicine topics:

Neurofibromatosis, Type 1 (Neurology)

Neurofibromatosis, Type 2 (Neurology)

Neurofibromatosis Type 1 (Radiology)

Neurofibromatosis Type 2 (Radiology)

Problem

Neurofibromatosis type 2 (NF2) does not appear to have any bone involvement or other orthopedic manifestations. As a result, it is not discussed in this article.

Spinal deformities have been noted to occur only in individuals with NF1. Deformities include both dystrophic and nondystrophic changes. The radiologic appearance of these dystrophic changes include the following features: scalloping of the posterior vertebral margins, severe rotation of the apical vertebra; widening of the spinal canal; enlargement of the neural foramina; defective pedicles; a paraspinal mass; spindling of the transverse process; and rotation of the ribs, which resembles twisted ribbons.

In some cases, these changes are the result of intraspinal pathology such as tumors,⁹ meningoceles, or dural ectasia. However, the changes may also occur in persons with entirely normal intraspinal contents. In these persons, primary bone dysplasia accounts for the dystrophic changes.¹⁰

Spinal changes in individuals with NF1 are usually divided into cervical, thoracic, lumbosacral, and spinal canal pathologies.

Cervical spine changes and associated complications

Features of the cervical spine in patients with NF1 have not received enough attention in the literature. Cervical abnormalities occur much more frequently when a scoliosis or kyphoscoliosis is present in the thoracolumbar region, in which case the examiner's attention is focused on the more obvious deformity.

The manifestations of NF1 can be observed as dystrophic changes in the vertebral body, or they can be due to pathologic alignment. The most common abnormality observed is a severe cervical kyphosis, which in itself is highly suggestive of the disorder. In the study of Yong-Hing et al, 17 patients with NF1 were found to have cervical abnormalities.¹¹ Of these, 7 were asymptomatic, while the rest had either limited motion or pain in the neck. Four patients had neurologic deficits, which were probably attributed to cervical instability. Four of the 17 patients required fusion of the cervical spine. Curtis described 8 patients with paraplegia and NF1. Paraplegia in 4 of these patients was due to cervical spine instability or intraspinal pathology in the cervical spine.¹²

Attention also should be paid to the C1-2 region. Isu described 3 patients with NF1 who had C1-2 dislocation with neurologic deficit, and all improved after decompression or fusion. No bony changes in the C1-2 relationship were observed on flexion-extension views in any of these patients. Most of the problems in the cervical spine in this study occurred after excision of the tumors, which included resection of the laminae and posterior elements. Postoperatively, the spine is unstable and tends to develop progressive kyphosis.

All patients with NF1 who undergo surgery, who require endotracheal anesthesia, who undergo halo traction, or who present with neck tumors should undergo a cervical radiographic series. If subluxation is suspected, tomograms, CT scans, and/or MRIs are appropriate. Other reasons for obtaining cervical spinal radiographs in a patient with NF1 include the evaluation of torticollis and dysphagia.

Scoliosis

Scoliosis is the most common osseous defect associated with NF1. It may vary in severity from mild and nonprogressive to severe curvatures. The cause of this spinal deformity is unknown, but some have suggested that it is secondary to endocrine disturbances, mesodermal dysplasia, and osteomalacia (a localized neurofibromatous tumor eroding and infiltrating bone).

In a general orthopedic clinic, 2% of patients with scoliosis have neurofibromatosis, whereas in a neurofibromatosis clinic, 10-20% of patients have some disorder of the spine. All preadolescent children with neurofibromatosis should be evaluated with scoliosis screening, or the bend test, to exclude a spinal deformity, which usually occurs earlier in children with neurofibromatosis.

Two primary types of scoliosis are observed in persons with neurofibromatosis. Dystrophic scoliosis is the short-segmented, sharply angulated type that includes fewer than 6 spinal segments. It has a tendency to progress to a severe deformity.^13,14 The second type of curvature, the nondystrophic, is similar to the idiopathic curvature observed in adolescents. This form usually involves 8-10 spinal segments. The deformity is most often convex to the right; however, this is not consistent.

Meningoceles, pseudomeningoceles, dural ectasia, and dumbbell lesions are all related to the presence of neurofibroma or abnormal pressure phenomena in and around the spinal canal neuraxis. High-volume myelography or MRI should be used in the investigation of all dystrophic curves prior to treatment. Occasionally, these intraspinal elements may directly compromise the cord when instrumentation and stabilization are attempted, or they may cause erosive changes in the bone, preventing primary fusion.

Dystrophic curvatures of less than 20° should be observed for progression at 6-month intervals. For persons with curvature greater than 20-40° of angulation, a posterior spinal fusion with some form of segmental spinal instrumentation is recommended.¹⁵ Curves greater than 50° should be treated with anterior and posterior fusion. Oblique radiographs are obtained every 6 months to exclude pseudarthrosis. Brace treatment has not been effective. For the very young child, early fusion causes minimal stunting of growth. Nondystrophic curvatures of less than 20° should be observed, 20-35° should be braced, and 35° and greater should be stabilized.

Kyphosis

Kyphosis observed in individuals with NF1 is distinguished by acute anteroposterior angulation. Vertebral bodies may be deformed so severely that they are confused with congenital deformities. Bracing is recommended for those patients with kyphosis less than 50°. In those with curvatures greater than 50°, anterior surgery (intervertebral diskectomy, rib strut grafting, and bone chip grafting) is recommended, followed by posterior segmental instrumentation.

Once a curvature exceeds 70°, indefinite bracing may be required, even after spinal surgery, until solid union is achieved. Because of the association of paraplegia with kyphosis, physicians have tended to perform laminectomy. Laminectomy alone for kyphotic cord compression is absolutely contraindicated. The offending neurofibromas are usually anterior, and decompression should be performed anteriorly. The removal of the posterior element predisposes the spine to instability by removing valuable bone stock required for fusion. Spinal fusion should be performed after laminectomy.

Cervical spine involvement

The cervical spine should be evaluated with the initial scoliosis investigation. Evidence of dystrophic changes may be present on a true lateral view. Progressive cervical kyphosis is usually apparent after excision of the posterior elements. The patient presents with a neck deformity after anterior and posterior excision of a neck mass. If any suspicious area is noted on plain radiographs, right and left oblique views should be obtained to look for widening of the neuroforamina. These may represent dumbbell lesions (ie, widening of the neuroforamina caused by the exit of a neurofibroma from the spinal canal).

Spondylolisthesis

Spondylolisthesis is a rare disorder that is most often associated with a pathologic luxation of the vertebra because of erosions of the pedicles or pars from foraminal neurofibroma or dural ectasia. Surgery is indicated with the progression of the spondylolisthesis from grade II to grade III or with the presence of pathologically elongated pedicles with or without pain. Anterior and posterior stabilization is recommended for the treatment of a progressive deformity.

Tibial dysplasia

Tibial bowing occurs in 1 per 140,000 live births. The bowing associated with NF1 is always anterolateral. The deformity may appear before other protean manifestations such as café-au-lait spots. It is usually evident within the first year of life, with a fracture not uncommonly occurring by the time the child is aged 2-2.5 years. Conversely, posteromedial congenital bowing, or kyphoscoliosis tibia, is a benign condition.

Tibial bowing associated with bilateral skin dimples, ring constrictions, and foot deformities is rarely associated with NF1. The management of this anterolateral bowing deformity is most frustrating. Unlike scoliosis, treatment of congenital pseudarthrosis of the tibia does not appear to be more successful when it is initiated early.

The 2 basic types of bowing are the nondysplastic type and the dysplastic type.

• Nondysplastic, type I
  • Anterolateral bowing with increased bony density
  • Sclerosis of the medullary canal
  • Possibility of this type converting to dysplastic after osteotomy to correct the angulation
• Dysplastic, type II
  • Anterolateral bowing with a failure of tubulation
  • Anterolateral bowing with cystic prefracture or canal enlargement from previous fracture
  • Frank pseudarthrosis and atrophy with "sucked candy" narrowing of the ends of the 2 fragments

Frequency

NF1 is common and affects 1 in 4,000 individuals. NF2 occurs more rarely, with an estimated incidence of 1 case in 100,000 individuals.

Etiology

NF1 is one of the most common single-gene disorders known to humans. Approximately 50% of all NF1 cases are the result of new mutations; this is 100-fold higher than the usual mutation rate for a single locus and may reflect the huge size of the NF1 locus (estimated to be 350,000 base pairs). Most genes are several tens of thousands of base pairs, and the largest known, the gene for Duchenne muscular dystrophy, encompasses 2.5 million base pairs.

Prenatal testing is now possible in some families, but its use is minimal because, in most patients, mutations have not been easy to identify. The manifestations of NF1 vary from one person to another; however, each individual who carries the gene eventually exhibits some clinical features of the disease. The penetrance for NF1 nears 100%. Cloning of the gene has allowed the creation of animal models that ultimately may be used to develop more-effective therapy against the disease.

Pathophysiology

Currently, exactly how the genetic defect causes the formation of the lesions is not known.

Presentation

In 1987, the Consensus Development Conference on Neurofibromatosis at the National Institutes of Health concluded that the diagnosis of NF1 can be assigned to a person with 2 or more of the following criteria:

• More than 6 café-au-lait spots measuring at least 15 mm in adults and 5 mm in children (Café-au-lait spots are found in more than 50% of individuals with NF1.)
• At least 2 or more neurofibroma of any type or at least 1 plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Optic glioma¹⁶
• Two or more Lisch nodules (iris hamartomas)
• A distinctive bony lesion, such as sphenoid wing dysplasia or thinning of a long bone with or without pseudoarthrosis
• A first-degree relative with NF1, as suggested by these criteria

These criteria are useful, even in young children. Since the consensus panel meeting, specific learning disabilities and abnormal findings, as shown on MRI, have also been specifically associated with NF1, especially in children. Other disorders of pigmentation, such as McCune-Albright syndrome or Watson syndrome, can be confused with von Recklinghausen disease.

NF1 can be clearly distinguished from central neurofibromatosis or NF2, which is also an autosomal dominant disorder. However, NF2 occurs more rarely, affecting an estimated 1 in 100,000 individuals. Characteristically, in individuals with NF2, bilateral schwannomas of the vestibular portion of the eighth cranial nerve are present, but schwannomas of other peripheral nerves, meningiomas, and ependymomas are also common.¹⁷ None of the eighth cranial nerve tumors is found in persons with NF1. NF2 has been localized on the long arm of chromosome 22, and the gene was recently cloned.

Indications

Scoliosis

For persons with curvature greater than 20-40° of angulation, a posterior spinal fusion with some form of segmental spinal instrumentation is recommended. Curves greater than 50° should be treated with anterior and posterior fusion. For the very young child, early fusion causes minimal stunting of growth. Nondystrophic curvatures of less than 20° should be observed, those of 20-35° should be braced, and those of 35° and greater should be stabilized by means of anterior and posterior fusion with segmental spinal instrumentation.

Kyphosis

In patients with curvatures greater than 50°, anterior surgery (intervertebral diskectomy, rib strut grafting, and bone chip grafting) is recommended, followed by posterior segmental instrumentation. Once a curvature exceeds 70°, indefinite bracing is required, even after spinal surgery.

Because of the association of paraplegia with kyphosis, physicians have tended to perform laminectomy. Laminectomy alone for kyphotic cord compression is absolutely contraindicated. The offending neurofibromas are usually anterior, and decompression should be performed anteriorly. The removal of the posterior element predisposes the spine to instability by removing valuable bone stock required for fusion. Spinal fusion should be performed after laminectomy.

Spondylolisthesis

Anterior and posterior stabilization is recommended for progressive deformity. Progression of spondylolistheses from grade II to grade II or the presence of pathologically elongated pedicles with or without pain are indications for surgery.

Tibial dysplasia

Obvious documented fracture is the only current direct indication for surgery in congenital tibial dysplasia. In children older than 5 years, subsequent bracing above the knee and articulated at the knee and ankle has been tremendously successful in managing angular deformities and preventing fractures. The surgical treatments include direct bone grafting, vascularized autogenous grafting, compression and distraction osteogenesis, and amputation.

Relevant Anatomy

The relevant anatomy is related to the diagnostic group, as described below.

Spinal involvement

Subcutaneous plexiform neurofibromas are often overlying the incision area. When posterior spinal fusion surgery is performed, one should be aware of the very thin laminae, which are often eroded by dural ectasia surrounding the spinal cord in the thoracic region. The laminae may be inadequate to accept hooks, and pedicle screws may be necessary. Considerable bleeding may occur with dissection around subcutaneous vascular tumors. The author recommends using monopolar and bipolar electrocautery for subperiosteal exposure of the posterior elements.

Posterior subperiosteal dissection is performed by using Bovie electrocautery dissection rather than subperiosteal elevators because of the potential presence of laminar defects or the possibility of inadvertently plunging through the lamina and directly damaging the spinal cord.

Anterior spinal dissection may be complicated by venous lakes and engorgement of saccular, almost sinusoidal, vessels, which are difficult to control in and around the vertebral bodies. Extensive blood loss from the blood vessels in the cancellous bone of the vertebral bodies is distinctly possible.

Diskectomies should be performed with Bovie dissection and use of a rongeur through the annulus fibrosis instead of sharp dissections of the endplate apophysis. Sharp dissections may cause significant bleeding from the often-friable cancellous matrix of the vertebral bodies.

Congenital tibial dysplasia

Subperiosteal dissection should be performed to expose the pseudoarthrosis site. Both ends are freshened, and a decision is made regarding whether an intermedullary rod or external fixation should be used. Use of an autologous iliac crest bone graft is highly recommended, regardless of the surgical procedure. A vascularized fibular bone graft is another option.

Also see Introduction, Problem.

Contraindications

Spine

Bracing of progressive dystrophic curvatures is contraindicated simply because they have not been found to be effective. The authors' recent investigations have revealed a transition of idiopathic type curves to dystrophic types (modulation). Posterior spinal fusion alone is now believed to be contraindicated in young patients with progressive deformities. An anterior diskectomy and intravertebral fusion followed by posterior spinal fusion is the recommended procedure. The use of segmental fixation with instrumentation as well as postoperative bracing is highly recommended.

Limb-length inequality

Multiple attempts should be made to control growth in the hypertrophic limbs by means of epiphyseal arrest. A shortening osteotomy of the longer side is rarely successful and strongly contraindicated. The healing of the osteotomy may be delayed and nonunion leading to pseudoarthrosis may occur. Stapling of the longer limb has resulted in marginal successes, but a shortening osteotomy is strongly contraindicated. Lengthening the opposite side when the difference is less than 7 cm may be an alternate approach, but this is considered risky.¹⁸

Congenital tibia dysplasia

The elective correction of angular deformities for cosmesis is strongly contraindicated. The risk of pseudoarthrosis is too great. Consequent bracing and protection until skeletal maturity is highly recommended.¹⁸

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