Movement Disorders in Two Children with DNM1L-related Mitochondrial Cytopathy
Manasa Sudheendra1, Haleigh Stafford1, Naomi Kass1, Mered Parnes1, Mariam Hull1
1Texas Children's Hospital/ Baylor College of Medicine
Objective:
We describe two patients who presented with dystonia and were found to have DNM1L mutations. We describe their presentation, clinical course and management with accompanying video.
Background:
Dynamin like protein (DNM1L) is a member of the dynamin superfamily of GTPases and encodes proteins that mediate mitochondrial and peroxisomal division. Mutations in DNM1L have been implicated in various neurological phenotypes including encephalopathy, epilepsy, hemiparesis, ophthalmoplegia and peripheral neuropathy, however few cases have been published, thus the phenotypic spectrum is not well understood.
Design/Methods:
We describe an 8-year-old boy with history of developmental regression at 3 months, and further regression with illness. He had irregular distal hand postural and kinetic tremor, mostly but also some proximal component, stiff-legged gait with equinovarus posturing, and painful toe flexion dystonia. Trio-WES revealed a de-novo variant in DNM1L. He was treated with carbidopa/levodopa with significant improvement in dystonia, tremor, balance and gait.
We describe a 12-year-old girl with history of developmental delay noted at 9 months of age, developmental regression with loss of ability to walk around 2 years of age due to weakness, action tremor, strabismus, rigidity, and chorea. MRI brain showed asymmetric, irregular round areas of T1 hyperintensity in the bilateral thalami. Muscle biopsy was consistent with metabolic myopathy. Trio-WES revealed a novel, de novo pathogenic variant and one variant of unknown significance in DNM1L. She was treated with carbidopa/levodopa resulting in improved gait and ability to ambulate with a walker.
Results:
DNM1L mutations present with a variety of neurologic symptoms. These patients showed significant improvement with levodopa-carbidopa in gait, tremor, and dystonia suggesting some degree of dopa-responsiveness.
Conclusions:
This case series describes several movement disorders seen in two patients with DNM1L mutations. Furthermore, these cases suggest levodopa may provide benefit in treatment of gait abnormalities, painful dystonia, rigidity, and tremor that may be present within this condition.
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