To describe a patient with a unique phenotype reflecting a progressive neurologic disorder associated with a novel, de novo mutation in the DNM1L gene.

The dynamin 1-like gene (DNM1L, formerly DRP1, DLP1) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. Several reports have described pathogenic variants (mutations) in DNM1L associated with hypotonia, cognitive impairment and refractory epilepsy. More recent reports have expanded the phenotype and include movement disorders, such as severe juvenile parkinsonism and dystonia. 

We describe a 12-year-old girl with cognitive deficits, bradykinesia, muscle weakness, gait impairment, and progressive ophthalmoparesis, in addition to mild dystonia, tremor, chorea, and ataxia. Muscle biopsy was consistent with mitochondrial myopathy. MRI brain showed asymmetric, irregular round areas of T1 hyperintensity in both thalami, also suggestive of mitochondrial disease. Her course has been marked by periods of acute exacerbation of weakness necessitating hospital admission. Bradykinesia improves with levodopa on examination. By history, generalized stiffness improved markedly at age 3 after treatment with levodopa was initiated, leading to a presumptive diagnosis of dopa-responsive dystonia at that time.

Recent reanalysis of prior whole exome sequencing revealed a novel, de novo pathogenic variant (c.762_763insAA, p.N254fs) and one variant of unknown significance (c.1778T>C, p.L593P) in the DNM1L gene.

This case illustrates a new phenotype associated with mutations in DNM1L manifested by a childhood-onset movement disorder associated with other debilitating neurologic symptoms.