Background Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder characterized by a potential multisystemic involvement. The musculoskeletal system is frequently affected (i.e.: scoliosis, thorax anomalies, tibial dysplasia). The segmental overgrowth of lower limb (SOLL) is rarely reported, albeit it severely affects patients’ wellbeing. The resulting leg length discrepancy (LLD) negatively impacts the development of the musculoskeletal system and may require appropriate correction, which could include surgery. Our objective was to evaluate the prevalence, the management, and the outcomes in patients with SOLL and NF1. We retrospectively evaluated 553 pediatric patients seen between 1992 and 2024 with a diagnosis of NF1. All patients presenting with SOLL were included in the study. For each patient, we assessed the degree of LLD at the initial evaluation, at the time of surgery (if any), at the point of maximum discrepancy, and at last visit. Demographic data, associated deformities, presence and location of plexiform neurofibroma (PN) were registered. Each patient and/or their parents were also evaluated using the Gait Outcome Assessment List for lower-limb differences (GOAL-LD) questionnaire to assess the health-related quality of life of pediatric patients with LLD. Results 7 patients (4 males) with a mean age at diagnosis of SOLL of 4.67 years met our inclusion criteria. The detected discrepancies ranged from 0.5 cm to 6 cm (mean 4.30). Five children underwent surgery for the discrepancy (3 with epiphysiodesis and 2 with external fixation limb lengthening). All patients but one presented a plexiform neurofibroma in the district of SOLL that has been treated by selumetinib in 3 cases. Two patients were treated conservatively using lifted insoles. The GOAL-LD questionnaire revealed low scores in all the domains evaluated (function and mobility, pain and fatigue, physical and recreational activity, gait appearance, use of braces and walking aids, body image, and self-esteem). Conclusions SOLL-related LLD in patients with NF1 is a complex condition with significant impact on quality of life. Outcomes are often suboptimal, underlying the need for individualized, multidisciplinary management and structured follow-up. Early detection of progression is crucial to guide timely therapeutic decisions. Further prospective, multicenter studies are needed to better clarify pathogenic mechanisms and to develop standardized treatment protocols.
Prevalence and management of lower limb segmental overgrowth in patients with NF1: an observational study
Santoro, Claudia;Martin, Gabriele;Itro, Annalisa;Piluso, Giulio;Paoletta, Marco;Liguori, Sara;Moretti, Antimo;Perrotta, Silverio;Toro, Giuseppe
2026
Abstract
Background Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder characterized by a potential multisystemic involvement. The musculoskeletal system is frequently affected (i.e.: scoliosis, thorax anomalies, tibial dysplasia). The segmental overgrowth of lower limb (SOLL) is rarely reported, albeit it severely affects patients’ wellbeing. The resulting leg length discrepancy (LLD) negatively impacts the development of the musculoskeletal system and may require appropriate correction, which could include surgery. Our objective was to evaluate the prevalence, the management, and the outcomes in patients with SOLL and NF1. We retrospectively evaluated 553 pediatric patients seen between 1992 and 2024 with a diagnosis of NF1. All patients presenting with SOLL were included in the study. For each patient, we assessed the degree of LLD at the initial evaluation, at the time of surgery (if any), at the point of maximum discrepancy, and at last visit. Demographic data, associated deformities, presence and location of plexiform neurofibroma (PN) were registered. Each patient and/or their parents were also evaluated using the Gait Outcome Assessment List for lower-limb differences (GOAL-LD) questionnaire to assess the health-related quality of life of pediatric patients with LLD. Results 7 patients (4 males) with a mean age at diagnosis of SOLL of 4.67 years met our inclusion criteria. The detected discrepancies ranged from 0.5 cm to 6 cm (mean 4.30). Five children underwent surgery for the discrepancy (3 with epiphysiodesis and 2 with external fixation limb lengthening). All patients but one presented a plexiform neurofibroma in the district of SOLL that has been treated by selumetinib in 3 cases. Two patients were treated conservatively using lifted insoles. The GOAL-LD questionnaire revealed low scores in all the domains evaluated (function and mobility, pain and fatigue, physical and recreational activity, gait appearance, use of braces and walking aids, body image, and self-esteem). Conclusions SOLL-related LLD in patients with NF1 is a complex condition with significant impact on quality of life. Outcomes are often suboptimal, underlying the need for individualized, multidisciplinary management and structured follow-up. Early detection of progression is crucial to guide timely therapeutic decisions. Further prospective, multicenter studies are needed to better clarify pathogenic mechanisms and to develop standardized treatment protocols.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
