Impaired Bone Healing and Fracture Complications during Limb Lengthening in a Neurofibromatosis Type 1 Patient Receiving Selumetinib: Case Report and Literature Review.

INTRODUCTION: Neurofibromatosis Type 1 (NF1) is a genetic disorder that may lead to the development of plexiform neurofibromas (Pns). Selumetinib, a selective mitogen-activated protein kinase (MEK1/2) inhibitor, has shown clinical benefit in shrinking inoperable PNs. However, its long-term effects on the skeleton remain unclear. This case describes impaired bone healing and pathological fractures following limb lengthening in a child with NF1 receiving prolonged selumetinib therapy.

CASE REPORT: A 5-year-old boy with genetically confirmed NF1 and left lower limb PN-induced overgrowth presented with a 4.5 cm limb length discrepancy. The patient had been receiving selumetinib (20 mg twice daily) without a clinically significant reduction in the size of the PNs. Lengthening was performed on a short healthy lower leg with an external fixator that did not include the femur. A distal femoral fracture occurred 3 weeks postoperatively on the same side as the lower leg lengthening was performed, and was treated with K-wire fixation. Despite healing, a refracture occurred 2 months later. In addition, delayed bone healing was observed for the tibial lengthening regenerate, and progressive valgus deformity and fibular migration developed. Selumetinib was discontinued due to adverse effects and suspected contribution to impaired bone healing.

CONCLUSION: In pediatric NF1 patients treated with selumetinib, fracture and impaired bone healing may be rare side effects, especially during limb lengthening. These findings highlight the importance of closely monitoring bone health in NF1 patients on MEK inhibitors, particularly when undergoing orthopedic procedures.