Severe Headbanging Responsive to Levodopa in a Child With FOXP1 Syndrome

We report a 9-year-old female with FOXP1 syndrome due to a de novo in-frame deletion in the FOXP1 gene. The child has a severe neurodevelopmental disorder including global developmental delay and autism spectrum disorder. At age 2, she developed severe headbanging, which was progressive and did not respond to multidisciplinary, behavioral management strategies or to multiple medication treatments. Although repetitive behaviors are frequent in patients with FOXP1 variants, severe and intractable headbanging has not been reported to date. Levodopa/carbidopa was prescribed at age 7 due to progressive foot dystonia and contracture development. This treatment was not clearly beneficial for the dystonia and foot position, but immediate improvement in headbanging was observed and the response sustained for over 19 months. The FOXP1 gene codes for a transcriptional regulator protein that has been shown to regulate the development of brain and spinal motor neurons, and some evidence has linked FOXP1 to the differentiation of midbrain dopaminergic neurons via the homeobox protein PITX3, thus providing a potential mechanism for the observed benefit. This case report may provide expansion of the behavioral phenotype associated with FOXP1 variants and suggests avenues for further animal research and/or clinical trial of levodopa in individuals with FOXP1 variants.