summary Neurofibromatosis is an autosomal dominant disorder caused by a mutation in the NF1 gene that codes for the neurofibromin protein that typically presents with skin lesions, lower and upper extremity deformities, and spinal involvement. Diagnosis is made with the NIH Consensus Development Conference Statement criteria with the presence of a combination of cafe-au-lait spots, neurofibromas, freckling in axillary/inguinal region, optic glioma, lisch nodules, and the presence of a 1st degree relative with NF-1. Treatment depends on presence and severity of forearm, lower extremity or spinal deformity. Epidemiology Incidence 1:3,000 births for NF1 Anatomic location extremity deformities congenital anterolateral bowing and pseudoarthrosis of tibia/ fibula and forearm hemihypertrophy spine involvement scoliosis & kyphosis atlantoaxial instability Etiology Genetics autosomal dominant (AD) mutation in NF1 gene on chromosome 17q11.2 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 anterolateral bowing of tibia bowing of forearm bones with obliteration of medullary cavity ulnar pseudoarthrosis radius pseudoarthrosis neoplasias Diagnosis 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 Inoperable tumors may be treated with selumetinib 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 Prognosis Studies show between 8-10 years of decreased life expectancy compared to general population High incidence of malignancy and hypertension