MEK Inhibitor-Induced Dropped Head Syndrome in Pediatrics

Abstract Background MEK inhibitors are increasingly used as targeted therapies in several oncologic indications including pediatric neuro-oncology. While these agents are generally well tolerated, rare neuromuscular toxicities have been described in adults. Dropped head syndrome, characterized by severe weakness of the cervical extensor muscles resulting in a chin-on-chest deformity, has been reported in adults receiving MEK inhibitors but has not been described in children. Case Summary A case of dropped head syndrome in a pediatric patient with intracranial neoplasm on MEK inhibitor monotherapy is described. The patient presented with acute, debilitating neck and proximal muscle weakness that significantly impaired activities of daily living. Extensive evaluation revealed no alternative etiology, and imaging showed stable intracranial disease. Laboratory studies demonstrated mild elevations in creatinine phosphokinase. Symptoms improved rapidly following discontinuation of the MEK inhibitor, with complete resolution and return to neurologic baseline. A literature search revealed several adult cases of MEK inhibitor-associated dropped head syndrome, and one suspected pediatric case initially described as myalgia. Similarities among reports include functional impairment, relatively short onset from drug initiation (with notable exceptions), mild elevation in creatinine phosphokinase, and prompt resolution with drug discontinuation. Conclusion Dropped head syndrome is a rare but potentially severe toxicity associated with MEK inhibitor therapy and can occur in pediatric patients. Prompt recognition and discontinuation of the offending agent may lead to rapid and complete recovery. As the use of MEK inhibitors continues to expand in children, awareness of this toxicity is essential to facilitate timely diagnosis and management.