Neurofibromatosis

Muhammad Abdelghani

Definition

• Neurofibromatosis is one of the commonest single gene disorders affecting the skeleton.

Types

• Two types are recognized:– Type 1 (NF-1): Von Recklinghausen’s

disease.– Type 2 (NF-2): The less common type

Type 1 (Von Recklinghausen’s disease; peripheral NF)

• Incidence: about 1 in 3500 live births• Abnormal gene: The abnormality is

located in the gene that codes for neurofibromin on chromosome 17.

• Pattern of inheritance: Autosomal dominant with 100% penetrance.

• Characteristic lesions: Neurofibromata (Schwann cell tumours) & patches of skin pigmentation (café-au-lait spots).

• Musculoskeletal abnormalities: seen in almost half of thoses affected.

Type 2 (Central NF)

• Incidence: much less common than type 1 (1 in 50000 live births).

• Abnormal gene: The abnormality is associated the gene that codes for schwannomin on chromosome 22.

• Pattern of inheritance: Autosomal dominant (Like NF-1).

• Characteristic lesions: Intracranial lesions (e.g. bilateral acoustic neuromas and meningiomas) are usual (unlike NF-1).

• Musculoskeletal abnormalities: rare (unlike NF-1).

Clinical features of NF-1

• Almost all patients have the typical widespread patches of skin pigmentation and multiple cutaneous neurofibromata (which usually appear before puberty).– Less common is a single

large plexiform neurofibroma, or an area of soft-tissue overgrowth in one of the limbs.

Clinical features of NF-1

• A child or adolescent may present with – Scoliosis (usually a very short, sharp

curve)– Localized vertebral abnormalities (e.g.

scalloping of the posterior aspects of vertebral bodies, erosion of pedicles, intervertebral foraminal enlargement & pencilling of the ribs at affected levels).

– Dystrophic spinal deformities (incl. deformities of cervical spine) are also seen.

Clinical features of NF-1

• Congenital tibial dysplasia and pseudarthrosis are rare conditions, but almost 50% of patients with these lesions have some evidence of neurofibromatosis.– Pseudarthrosis of the tibia starts with

antrolateral bowing of the tibia in infancy with a fracture when the patient begins walking.

Clinical features of NF-1

• Malignant change occurs in 2-5% of affected individuals and is the most common complication in older patients.

Diagnostic criteria for NF-1• The diagnostic criteria are met if 2 or

more of the features listed are present:– Six or more café au lait macules >5 mm in

greatest diameter in prepubertal individuals and those >15 mm in greatest diameter in postpubertal individuals

– Two or more neurofibromas of any type or 1 plexiform neurofibroma

– Freckling in the axillary or inguinal regions– Optic glioma– Two or more Lisch nodules (iris

hamartomas)– A distinctive osseous lesion (e.g. sphenoid

dysplasia or thinning of the long bone cortex with or without pseudoarthrosis).

– A first-degree relative with NF-1 according to the above criteria

Orthopaedic manifestations of NF

• Pseudarthrosis of long bones:– Typically the tibia, but also the ulna, radius

and clavicle.– This is the most common orthopaedic

manifestation of NF.

• Scoliosis• Limb overgrowth:

– Limb overgrowth can range from disproportional growth of a single digit (macrodactyly) to one or more extremity.

Limb overgrowth

– Overgrowth of an extremity may be related to changes in the soft tissues (e.g. hemangiomatosis, lymphangiomatosis, elephantiasis, and beaded plexiform neurofibromas.

– The zones of overgrowth in the bone and soft tissues are usually unilateral, involving the extremities or the head and neck.

– The osseous changes characteristically cause the bone to elongate with wavy irregularity or thickening of the cortex.

The segmental hypertrophy and overgrowth in this

child are related to subperiosteal bone

overgrowth. The patient presented at 2.5 years of

age with trauma and subperiosteal bone

proliferation. The resulting overgrowth and dysplasia progressed over a 3-year period. Attempts at distal

femoral and proximal tibial epiphysiodesis were

unsuccessful.

Spinal deformities

• Spinal deformities noted in NF-1 include both dystrophic and nondystrophic changes in the vertebral bodies.

Spinal deformities

• The radiographic appearance of nondystrophic deformity consists of wedging, angulation, and rotation similar to that seen in idiopathic deformities.

Spinal deformities

• Radiologic appearance of dystrophic changes includes: 1. Scalloping of posterior vertebral margins, 2. Severe rotation of the apical vertebrae, 3. Vertebral wedging, 4. Widening of the spinal canal, 5. Enlargement of the neural foramina, 6. Widened interpediculate distance, 7. Defective pedicles, 8. Presence of a paraspinal mass, 9. Spindling of the transverse process, & 10.Rotation of the ribs resembling a twisted

ribbon (‘penciling’).

Spinal deformities

• Rib penciling is diagnosed when a rib is smaller in diameter than the midportion of the 2nd rib.

• These changes may be due to intraspinal lesions, such as tumors, meningoceles, and dural ectasia.

• However, the changes may occur even if the intraspinal contents are entirely normal.

• In these cases, the dystrophic changes have been explained as a primary bone dysplasia.

Nondystrophic-appearing changes

in the vertebral body associated with

spinal deformities. The appearance is very similar to that

of idiopathic scoliosis.

Myelogram shows widening of the spinal canal and the characteristic short, segmented, sharply angulated

deformity associated with

neurofibromatosis.

Treatment

• Congenital pseuarthrosis of the tibia– Treatment is likely to be prolonged and fraught

with difficulty.– Spontaneous union is rare.– Simple immobilization will certainly fail, and

internal fixation with bone grafting succeeds only very occasionally.

– Better results have been achieved by correcting the deformity, bone grafting the fracture and immobilizing the tibial fragments in a circular external fixator (Ilizarov technique).

– Success has also been claimed for excision of the abnormal segment and replacement by a vascularized fibular graft.

Treatment

• Scoliosis– The severity of spinal deformity associated with

neurofibromatosis varies from very mild (and not requiring any form of treatment) to the most marked manifestations accompanied by skin lesions, multiple neurofibromatosis and bony dystrophy affecting the vertebrae and ribs.

– Mild cases are treated as for idiopathic scoliosis.– More severe deformities will usually need

combined anterior and posterior instrumentation and fusion.

– As with other forms of skeletal neurofibromatosis, graft dissolution and pseudarthrosis are not uncommon.

Treatment

• Limb overgrowth– Treatment is extremely empirical

and individualized. – Some combination of

epiphysiodesis, debulking, and neurofibroma resection is recommended