Lecture on the orthopaedic aspects of neurofibromatosis by Dr Muhammad Abdelghani

1. Neurofibromatosis
Muhammad Abdelghani

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

3. Types
• Two types are recognized:
– Type 1 (NF-1): Von Recklinghausen’s
disease.
– Type 2 (NF-2): The less common type

4. 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.

5. 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).

6. 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.

7. 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.

8. 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.

9. Clinical features of NF-1
• Malignant change occurs in 2-5% of
affected individuals and is the most
common complication in older patients.

10. 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

11. 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.

12. 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.

13. 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.

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

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

16. 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’).

17. 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.

18. Nondystrophic-
appearing changes
in the vertebral body
associated with
spinal deformities.
The appearance is
very similar to that
of idiopathic
scoliosis.

19. Myelogram shows
widening of the
spinal canal and
the characteristic
short, segmented,
sharply angulated
deformity
associated with
neurofibromatosis.

20. 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.

21. 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.

22. Treatment
• Limb overgrowth
– Treatment is extremely empirical and
individualized.
– Some combination of epiphysiodesis,
debulking, and neurofibroma resection
is recommended