Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1

Abstract

Five percent of individuals with neurofibromatosis type 1 (NF1) present with congenital long bone pseudarthrosis (PA). In large series, 50-80% of patients with congenital long bone PA also have NF1. Very little information exists on the natural history and pathogenesis of PA in NF1. This report is a descriptive analysis of a large series of patients with NF1 and tibial bowing or PA. Study A is a case-control study using the National Neurofibromatosis Foundation International Database (NNFFID). Eighty-five patients with PA were compared to a control group from the same database. There was a statistically significant male predominance of NF1 cases with PA (54 males to 31 females), compared to controls (85 males to 87 females) (chi2 = 4.0, P = 0.046, using a two-tailed test with Yates' correction). There was no significant difference in the clinical presentation of NF1 manifestations in NF1 patients with PA than in NF1 patients without PA. Of the affected individuals with PA, there were 24 de novo cases and 21 familial cases (9 through maternal and 12 through paternal inheritance). Questions that could not be answered by Study A were addressed by a partially overlapping case-series report, Study B, in which data on 75 cases ascertained through questionnaires completed by NF center directors were collected. From Study B we determined that half of the patients who had a fracture sustained it before age 2, and approximately 16% of the pseudarthrosis patients had an amputation. Our data indicate a male predominance and no parent-of-origin effect. Male gender may be a susceptibility factor for pseudarthrosis in NF1.

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

“…Treatment for long bone pseudarthrosis is often unsatisfactory, requiring multiple surgeries or ultimately amputation [Coleman and Coleman, 1994;Stevenson et al, 1999;Traub et al, 1999;Wientroub and Grill, 2000]. The Consortium members thought that bracing after fracture should continue, delaying surgery until mid-childhood (%5-8 years of age).…”

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells

“…(6)(7)(8) The bone and orthopedic manifestations of NF1 can have a significant negative impact on patient quality of life. Generalized osteopenia and/or osteoporosis, scoliosis, compromised bone repair and pseudarthrosis, (9) and other bony manifestations can affect up to 50% of individuals with NF1. In particular, the orthopedic complications have a poor prognosis and can be recalcitrant to current medical interventions.…”

The use of anterolateral bowing of the lower leg in the diagnostic criteria for neurofibromatosis type 1

“…4 -6 The terminology used to describe the clinical and radiographic findings is often confusing, and the skeletal abnormalities exist along a continuum. Most commonly, the characteristic long bone dysplasia of NF1 is incorrectly de-scribed as "congenital tibial pseudarthrosis," although the process often involves the ipsilateral fibula as well and may affect the radius and/or ulna rather than the bones of the lower leg, 6 which we define as the portion of the body delimited by the knee and ankle. Reports of bowing and pseudarthrosis of the humerus and clavicle are rare but have also been published.…”