De novo DNM1L variant presenting with severe muscular atrophy, dystonia and sensory neuropathy

DNM1L encodes dynamin-related protein 1 (DRP1), a multi-domain GTPase essential for mitochondrial and peroxisomal division. Autosomal dominant and recessive variants in DNM1L cause encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1), which presents as a complex and clinically heterogeneous neurological disorder of variable severity, often accompanied by seizures. Clinical features are diverse, and no clear phenotype-genotype correlations were drawn to date. DNM1L-related sensory neuropathy has recently been reported as a predominant feature in one case with a de novo variant in the GTPase domain. Herein we present a second case with DNM1L-related sensory neuropathy as the predominant underlying feature without motor neuron involvement, which resulted in severe muscular atrophy and generalized dystonia.

Automated summary

Variants in the DNM1L gene cause a complex and clinically heterogeneous neurological disorder often accompanied by seizures, with no clear phenotype-genotype correlations drawn to date. Sensory neuropathy has been reported as a predominant feature in some cases, leading to severe muscular atrophy and generalized dystonia.