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Neurofibromatosis

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Topic updated on 06/12/16 10:36am
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
    • 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
      • decompressionASF & 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  

 

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Qbank (10 Questions)

TAG
(OBQ10.142) All of the following are associated with neurofibromatosis EXCEPT: Topic Review Topic

1. Smooth bordered café-au-lait spots
2. Posterior-medial bowing of the tibia
3. Short, sharp dystrophic scoliosis
4. Cutaneous neuromas
5. Autosomal dominant transmission from mutated neurofibromin gene

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TAG
(OBQ08.25) A 3-year-old boy presents with a leg deformity and multiple skin lesions. Lisch nodules were found on ophthalmologic exam. A clinical photograph and radiographs are shown in Figure A and B. What is the inheritance pattern and mutation that encodes for this condition. Topic Review Topic
FIGURES: A   B        

1. autosomal dominant; mutation in NF1 gene that codes for neurofibromin protein
2. autosomal recessive; mutation in NF1 gene that codes for neurofibromin protein
3. autosomal dominant; mutation of FGFR3 (fibroblast growth factor recepter)
4. autosomal recessive; mutation of FGFR3 (fibroblast growth factor recepter)
5. autosomal dominant; mutation of GS alpha protein

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TAG
(OBQ08.37) A 3-year-old boy presents with a forearm deformity. Radiographs are shown in Figure A. Ophthalmologic exam shows the lesion seen in Figure B. These finding are most consistent with which of the following conditions? Topic Review Topic
FIGURES: A   B        

1. Achondroplasia
2. Fibrous dysplasia
3. Osteogenesis imperfecta
4. Neurofibromatosis Type 1
5. Ollier's disease

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TAG
(OBQ08.226) A 60-year-old man presents with the hand condition shown in Figure A. The mass is resected with gross pathology and histopathology representations displayed in Figures B and C, respectively. What is the altered genetic etiology of this condition? Topic Review Topic
FIGURES: A   B   C      

1. COMP
2. Fibrillin
3. Neurofibromin
4. COL2A1
5. RUNX2/CBFA1

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TAG
(OBQ06.202) A 3-year-old boy presents with the skin lesion seen in Figure A and a leg deformity. Radiographs are shown in Figure B. What is the most appropriate first step in treatment? Topic Review Topic
FIGURES: A   B        

1. observation
2. bracing in total contact orthosis
3. intramedullary nailing with bone grafting
4. free fibular graft from contralateral side
5. external fixation using Illizarov techniques

PREFERRED RESPONSE ▶
TAG
(OBQ05.43) The diagnostic criteria for neurofibromatosis type I includes all of the following EXCEPT: Topic Review Topic

1. 2 or more neurofibromas
2. 6 or more cafe-au-lait macules
3. 2 or more Lisch nodules
4. freckling on the plantar surface of the feet
5. optic glioma

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TAG
(OBQ04.74) All of the following are clinical features of neurofibromatosis type I (NF-I) EXCEPT? Topic Review Topic

1. freckling in the axillae
2. optic glioma
3. 2 or more Lisch nodules
4. talipes equinus
5. cafe' au lait spots

PREFERRED RESPONSE ▶
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