Neurofibromatosis -

Reviewed by

Dr Andrew Mattin
MBBS | Accredited Orthopaedic Registrar

1:3000 newborns
Equal in sex and race
NF 1 – longarm of chromosome 17
- Gene product can be thought of as a tumor suppressor for cellular oncogene
- A neural crest disorder
- Cells migrate to parts of skin, brain, cord, nerves & adrenal glands
- Von Recklinghausen disease. (1882)
- Autosomal dominant disease. (Chromosome 17q11)
- Gene that codes for neurofibromin.
NF 2 – Chromosome 22.( Schwannomin.)
- Less common (1 in 50,000) but also autosomal dominant.
- Mosaics of the 1 and 2 do not demonstrate orthopaedic manifestations

Classification

NF 1
- 2 or more of – National Institute of Health Criteria.
  - at least 6 café au lait spots:
    - > 5mm in children,
    - > 15 mm in adults
  - 2 neurofibromas or 1 plexiform neurofibroma
  - freckling of the inguinal or axillary region
  - optical glioma
  - at least 2 lisch nodules (Iris condensations / hamartoma of the Iris)
  - a first degree relative with NF
  - a distinctive osseous lesion
    - sphenoid dysplasia
    - thinning of long bone cortex, with or without pseudarthrosis
NF 2
- Bilateral acoustic neuromas
  - Bilateral vestibular schwannomas.
- Paucity of peripheral findings
Diagnosis
- may be delayed due to variable age of presentation of signs

Clinical

Café au lait spots – discrete tan spots
- May take up to 1 year to appear
- Smooth
- Café au lait macules.
  - 99% have 6 or more that are >5cm in diameter by age of 1
  - Skin fold freckling. Axillary, inguinal, upper eye lids. 90% at 7 years
Neurofibroma
- Cutaneous – benign schwann cells with fibrous tissue
- Rapidly increasing numbers at puberty
- >80% at 20 years
- Plexiform neurofibromas
  - present at birth, highly infiltrative, darkly pigmented, limb gigantism or facial dysfigurement
  - prone to haemorrhage, pain, dysfiguration and malignant transformation.
  - 10-24%.
- NF-1 lifetime risk of malignant transformation 5%.
Axillary or inguinal freckling
Optic pathway glioma
Neurological delayed development
HTN, CVA, congenital heart disease, vasculopathy.

Orthopaedic Manifestations

Unusual scoliosis
- Scoliosis (Dystrophic, Non dystrophic)
Nonunion of a long bone
- congenital pseudoarthrosis of the tibia
Overgrowth of a part
Soft tissue tumors

General

Osteopaenia complicates treatment
Osteomalacia,
Effects cellular growth of neural tissue

Spine

Spinal deformity. 49% patients.
- intraspinal neurofibromatosis
- Dystrophic changes.
- Rib penciling,
- Dumbbell lesions
- Spindling of transverse process
- vertebral wedging
- foraminal enlargement
- widened interpedicular distance
- Dural ectasia
  - Circumferential dilation of the thecal sac and erodes surrouding bony structures.
  - Instability and deformity.
  - T2 MRI
- Vertebral scalloping
  - Anterior and posterior vertebral scalloping
  - >3mm in thoracic spine, >4mm in lumbar spine.
  - Posterior is most common
  - 63% scalloped vertebrae have associated dual ectasia or intraspinal neurofibroma.
- Cervical spine
  - 30% of NF-1 patients.
  - Cervical kyphosis, rotatory subluxation, dysplastic changes.
  - More common in dysplastic curves.
  - Spondylolisthesis, spondyloptosis.
  - Many are asymptomatic.
- Scoliosis
  - Dystrophic
    - Less common but more severe.
    - Short sharp angulated scoliosis.
    - Odd shaped vertebrae, codfish vertebrae
      - Scalloped posterior body
      - Eleveated neural foramen
      - Defective pedicles
      - Dural abnormality on MRI
      - Ribboned ribs
    - Relentless progression
    - Kyphosis common & can lead to neurologic dysfunction
  - Non dystrophic
    - Treat as idiopathic
    - Progresses at same rate as adolescent idiopathic scoliosis and same clinic appearance.
    - Earlier onset the worse prognosis.
    - Must monitor due to progression.
  - Management
    - All should be assessed with an MRI and CT.
      - Look for
        Intra/extra spinal neoplasm.
      - Repeat if any rapid progression.
    - Treatment according to deformity
      - Observation <20°
      - Bracing 20-40°
      - Fusing >40°
    - Dystrophic scoliosis.
      - High risk of progression and neurological compromise.
      - Early and aggressive surgical intervention has been advocated to prevent dystrophic curve progression.
      - Bracing has not been effective.
      - 6 monthly monitoring <20°.
      - 20-40° surgery.

Nonunion

May affect Tibia & fibula, radius, ulna, femur & clavicle
Congenital pseudoarthrosis of the tibia (CPT)
- CPT 1 in 250,000 births.
- 5% NF-1 have CPT.
- Anterolateral bowing of tibia that presents in the first year of life.
- Cortical thickening with narrowed intramedullary canal.
- Spontaneous fracture followed by pseudarthrosis.
- Treatment
  - Non operative.
    - Knee-ankle-foot orthosis to prevent fracture in dysplastic bone.
  - Operative
    - Principles
      - Variable union rates post operatively.
      - High refracture rate.
      - Common complication is non union, limb length discrepancy, refracture and valgus deformity.
    - Options
      - Bone grafting with IM fixation
        Telescoping nails
      - EXFIX,
        Ring external fixator
      - free vascularized fibular graft.
      - Resection of pseudarthrosis site.
      - Bone morphogenic proteins

Overgrowth

Any child with local gigantism has NF until proven otherwise
Overgrowth of some or all tissues in one region.
Unilateral segmental hypertrophy or gigantism.

Other lesions of bone:

Benign scalloping of the cortex
Cystic lesions
Permeative bone destruction

Malignancy

~ 5%
usually CNS
neurofibrosarcoma can occur

Other

Lisch nodules
HTN secondary to renal artery stenosis
50% have cognitive impairment
short big heads

Take home message

NF-1 autosomal dominant. 1 in 3,000.
Common orthopaedic manifestations which are challenging to manage.
Multidisciplinary approach is warranted as multi-organ involvement