Burden of disease and unmet needs associated with scoliosis in neurofibromatosis type 1: a systematic literature review.

A subset of patients with neurofibromatosis 1 (NF1), a rare autosomal dominant genetic condition, can develop skeletal manifestations. Scoliosis secondary to NF1 (hereafter referred to as NF1 scoliosis) is the most common and is expected to add substantial burden for patients with underlying NF1 due to its early age at onset, potentially rapidly progressive nature, and interplay with other NF1-related pathology (eg, spinal tumor development). Despite this, there are limited studies comprehensively evaluating the burden of NF1 scoliosis to help better characterize unmet need. To address this evidence gap, a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted to summarize current evidence around the epidemiology and natural history, clinical burden, humanistic burden, and management strategies in NF1 scoliosis. The prevalence of scoliosis among the patients with NF1 ranged widely (1.4%-70.6%) across 15 identified studies across 9 countries; this large range may in part be due to small cohort sizes and age range differences. Patients who were younger at NF1 scoliosis onset frequently had more rapid acquisition of dystrophic changes ("modulation") and experienced pronounced disease burden compared with those with later onset or non-dystrophic subtypes. Indeed, the clinical burden was pronounced in dystrophic NF1 scoliosis, where post-surgical spinal curve correction (most commonly measured using Cobb and kyphosis angles) was lost over a longer follow-up (range of 1.2%-5.8% correction loss over a mean range of 2.3-5.2 yr). This was associated with an increased need for revision surgeries and the risk of surgical complications. The PRISMA review suggested the need for additional management options in NF1 scoliosis, as surgery is the current standard of care. Importantly, this review highlighted evidence gaps among published evidence, emphasizing the need for further studies addressing the epidemiology, humanistic burden, and additional research areas to address unmet needs and improve outcomes in NF1 scoliosis.