# Prevalence and management of lower limb segmental overgrowth in patients with NF1: an observational study

## TL;DR

This study examines how often and how lower limb overgrowth occurs in children with NF1, and how it affects their quality of life and treatment outcomes.

## Contribution

The study provides insights into the prevalence, management, and outcomes of lower limb segmental overgrowth in NF1 patients.

## Key findings

- Seven out of 553 NF1 patients had segmental lower limb overgrowth with discrepancies ranging from 0.5 to 6 cm.
- Five patients underwent surgery, while two were treated conservatively with lifted insoles.
- GOAL-LD scores indicated poor quality of life across multiple domains in affected children.

## Abstract

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.

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).

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.