Neurofibromatosis - Pediatrics

Introduction

Neurofibromatosis is an autosomal dominant disorder of neural crest origin characterized by
- extremity deformities
  - congenital anterolateral bowing and pseudoarthrosis of tibia/ fibula and forearm
  - hemihypertrophy
- spine involvement
  - scoliosis & kyphosis
  - atlantoaxial instability
Epidemiology
- 1:3,000 births for NF1
Genetics
- autosomal dominant (AD)
- mutation in NF1 gene on chromosome 17q21
  - codes for neurofibromin protein
    - negatively regulates Ras signaling pathway
    - neurofibromin deficiency leads to increased Ras activity
    - affects Ras-dependent MAPK activity which is essential for osteoclast function and survival
- neurofibromatosis is the most common genetic disorder caused by a new mutation of a single gene
Associated conditions
- scoliosis (see below)
- anterolateral bowing of tibia
- bowing of forearm bones with obliteration of medullary cavity
  - ulnar pseudoarthrosis
  - radius pseudoarthrosis
- neoplasias
Prognosis
- normal life expectancy
- high incidence of malignancy and hypertension
Diagnostic criteria
- according to the NIH Consensus Development Conference Statement (1987) the diagnostic criteria for NF-1 are met in an individual if two or more of the following are found
  - six or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in postpubertal individuals.
  - two or more neurofibromas of any type or one plexiform neurofibroma.
  - freckling in the axillary or inguinal region.
  - optic glioma.
  - two or more Lisch nodules (iris hamartomas).
  - a distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis.
  - a first-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.is based on presence of both

Classification

NF1 (von Recklinghaussen disease)
- most common
NF2
- associated with bilateral vestibular schwannomas
Segmental NF
- features of NF1 but involving a single body segment

Presentation General

Presentation
- often presents with anterolateral bowing of tibia
- often presents with radial bowing
Physical exam
- verrucous hyperplasia
- hemihypertrophy
- cafe-au-lait spots
- axillary freckling
- scoliosis
- anterolateral bowing or pseudoarthrosis of tibia
- dermal Plexiform-type neurofibroma may be seen
- Lisch nodules are benign pigmented hamartomas of the iris

Neoplasias (Neurofibromatosis)

Neurofibromas (plexiform-type)
- is pathognomonic for NF1
- present in 4% of NF1
- may be dermal or in deep tissues
- often associated with limb overgrowth
- can undergo malignant transformation to neurofibrosarcoma
Wilms Tumor

Scoliosis (Neurofibromatosis)

Introduction
- spine is most common site of skeletal involvement in NF-1
  - scoliosis is NOT associated with NF-2
- can take two forms
  - idiopathic-like form (nondystrophic)
    - longer curve and treatment resembles that for idiopathic scoliosis
  - dystrophic form
    - curve is typically thoracic kyphoscoliosis with a short segmented and sharp curve with distorted ribs and vertebrae
    - usually recognized earlier than nondystrophic form
    - generally characterized by a sharp angular curve involving 4 to 6 vertebrae
Imaging
- radiographs show
  - vertebral scalloping
  - penciling of ribs (penciling of 3 or more ribs is a poor prognostic finding and associated with rapid curve progression)
  - enlarged foramina
- MRI
  - always obtain preoperative MRI to identify dural ectasia and dumbbell lesion (neurofibroma on nerve root)
  - paraspinal masses are useful to distinguish from idiopathic scoliosis
Treatment
- nonoperative
  - observation vs. bracing
    - bracing is not effective for dystrophic form
    - nondystrophic scoliosis in NF is treated like adolescent idiopathic scoliosis
- operative
  - decompression, anterior spinal fusion (ASF) & posterior (PSF) with instrumentation
    - indications
      - dystrophic scoliosis
        
        perform early in young children (< 7 yrs) with dystrophic curves
    - complications
      - high rate of pseudoarthrosis with PSF alone (40%)
        
        pseudoarthrosis rate still high with ASF&PSF (10%)
        
        some recommend augmenting the PSF with repeat iliac crest bone grafting 6 months after the primary surgery

Anterolateral Tibial Bowing (Neurofibromatosis)

Introduction
- epidemiology
  - anterolateral bowing is often associated with neurofibromatosis (NF1)
  - 50% with anterolateral bowing have NF1
  - 10% of NF1 have anterolateral bowing
- pathophysiology
  - may progress to pseudoarthrosis
- differentials for tibia bowing
  - anteromedial
    - associated with fibular hemimelia and congenital loss of lateral rays of the foot
  - posteromedial
    - usually congenital due to
      - abnormal intrauterine positioning
      - dorsiflexed foot pressed against anterior tibia
      - will develop leg length discrepancy
      - associated with calcaneovalgus deformity
Imaging
- radiographs
  - obtain AP and lateral of tib/fib

Treatment
- nonoperative
  - bracing in total contact orthosis
    - indications
      - bowing without pseudoarthrosis or fracture (goal is to prevent further bowing and fractures)
      - spontaneous remodeling is not expected
      - osteotomy for bowing alone is contraindicated
- operative
  - bone grafting with surgical fixation
    - indications
      - in bowing with pseudoarthrosis or fracture
  - amputation with prosthesis fitting
    - indications
      - three failed surgical attempts
      - Syme's often superior to BKA due to atrophic and scarred calf muscle in these patients
Techniques
- intramedullary nailing with bone grafting
  - resect pseudoarthrosis
  - insert Charnley-Williams rod
  - antegrade through resection site, then retrograde through the heel
  - < 4 y.o., extend fixation to calcaneus
  - 5-10 y.o., extend fixation to talus
    - 2 yrs. postop, typically a 2nd surgery to push rod proximally to free the ankle joint
- free fibular graft
  - often need to take fibula from contralateral side because ilpsilateral fibula is not normal
  - Illizarov's external fixation