Introduction: Neurofibromatosis type 2 (NF2) is autosomal-dominant tumor predisposition syndrome characterized by various multiple tumors, considerable functional disability and reduced life expectancy. NF2 patients` functional disability is mainly caused by hearing impairment, difficulty of swallowing, and gait disturbance. To the moment, clinical-genotype correlation analysis in NF2 have been reported regarding their mortality, the number of interventions, and the number of tumors. This study analyzes clinical-genotype correlation focusing on NF2 patients` functional disability, and clarify the clinical and genetic predictors of functional disability.
Methods: We conducted a retrospective analysis of 48 patients. Mutation analysis of germline DNA was performed with Sanger sequence and multiple ligation-dependent probe amplification (MLPA). By questioning when and how major functions impaired in each patient directly in the outpatient clinic, we analyze their functional outcome with respect to “disabled hearing or deafness”, “tube feeding”, and “complete dependence or bedridden”. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of functional disability.
Results: An NF2 gene alteration was identified in 31 patients (63.3 %) including truncating mutation (13:27.1 %), large deletion (4:8.3 %), splice site mutation (8:16.6%), missense mutation (5:10.4%), and somatic mosaic and undetected cases (18:37.5 %). In all clinical / genetic factors, “truncating mutation” (OR:3.712, 95%CI:1.02-13.39, p=0.045), “Somatic mosaic and Undetected case” (OR:0.007781, 95%CI:0.008-0.72, p=0.02521), and “Onset age?26 (OR:0.02186, 95%CI:0.001-0.39, p=0.009722)” had significant effects on each functional disability.
Conclusions: Functional outcomes in NF2 patients are predictable by considering age at diagnosis NF2, and germline mutation of NF2 gene.
Patient Care: Predicting functional outcomes in NF2 patients can improve their life long management.
Learning Objectives: By the conclusion of this session, participants should be able to 1)Describe the functional disability in NF2 patients, 2)Discuss about clinical-genetic correlation focusing on NF2 patients` functional disability, 3)Identify the clinical and genetic predictors of functional outcome in NF2 patients.