Clinical Phenotypic Spectrum and Multisystem Burden in Neurofibromatosis Type 1: A Retrospective Regional Cohort Study

Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder characterized by marked phenotypic heterogeneity. This study aimed to describe the clinical spectrum and multisystem burden of NF1 in a regional retrospective cohort. Methods: We retrospectively analyzed 77 unique patients with NF1 after removal of duplicate records. Demographic characteristics, cutaneous manifestations, extracutaneous involvement, therapeutic interventions, and disease evolution were evaluated. An exploratory multisystem burden score was calculated using six extracutaneous clinical domains. Results: Café-au-lait macules were present in all patients, axillary/inguinal freckling in 93.5%, cutaneous neurofibromas in 63.6%, and plexiform tumors in 28.6%. Psychiatric/behavioral (67.5%), skeletal (57.1%), ophthalmological (51.9%), and neurological (45.5%) involvement were common. More than half of the cohort had involvement of at least three extracutaneous domains. Plexiform tumors were more common in patients with progressive or unfavorable disease compared to those with stationary disease. Progressive or unfavorable evolution was associated with a higher frequency of plexiform tumors. Therapeutic interventions were reported descriptively. Conclusions: NF1 showed substantial multisystem involvement beyond its characteristic cutaneous manifestations. Plexiform tumors were associated with a more complex clinical course. The proposed exploratory multisystem burden score may facilitate descriptive assessment of disease breadth but requires prospective validation.