Clinical and Radiological Characterization of <scp>TEFM</scp>‐Associated Neurological Disorder

Transcription Elongation Factor Mitochondrial (TEFM) is a crucial component of the mitochondrial transcription machinery, playing a key role in regulating mitochondrial RNA (mtRNA) polymerase activity and ensuring efficient mitochondrial DNA transcription. Recent studies have identified pathogenic variations in the TEFM gene as the cause of a childhood-onset neurological disorder with varying severity. To date, only seven cases have been reported in the literature, all from a single study. We report the case of an adolescent male presenting with intellectual disability, behavioral abnormalities, intermittent ataxia, muscle fatigability, lateral rectus ophthalmoplegia, and generalized seizures, along with cerebellar and upper motor neuron signs, as well as unique neuroimaging findings. The intermittent nature of certain symptoms, along with muscle fatigability, resembled a neuromuscular junction (NMJ)-like disorder; however, the repetitive nerve stimulation test (RNST) was normal. Exome sequencing revealed a missense variant (c.469C>G, p.Pro157Ala), which was also observed previously in two Indian siblings. This case expands the phenotypic spectrum of TEFM-related mitochondrial disorders by presenting novel radiological findings not previously described. The identified missense variant may represent a population-specific variant and exhibits a recognizable phenotypic spectrum warranting consideration in individuals presenting with an NMJ-like disorder.