Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1

Five percent of individuals with neurofibromatosis type 1 (NF1) present wit h congenital long bone pseudarthrosis (PA), In large series, 50-80% of pati ents with congenital long bone PA also have NF1, Very little information ex ists 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 bow ing or PA, Study A is a case-control study using the National Neurofibromat osis Foundation International Database (NNFFID), Eighty-five patients with PA were compared to a control group from the same database. There was a sta tistically significant male predominance of NF1 cases with PA (54 males to 31 females), compared to controls (85 males to 87 females) (chi(2) = 4.0, P = 0.046, using a two-tailed test with Yates' correction). There was no sig nificant difference in the clinical presentation of NF1 manifestations in N F1 patients with PA than in NF1 patients without PA, Of the affected indivi duals 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 questionnair es completed by NF center directors were collected. From Study B we determi ned that half of the patients who had a fracture sustained it before age 2, and approximately 16% of the pseudarthrosis patients had an amputation. Ou r data indicate a male predominance and no parent-of-origin effect, Male ge nder may be a susceptibility factor for pseudarthrosis in NF1, Am. J, Med, Genet, 84:413-419, 1999, (C) 1999 Wiley-Liss, Inc.