Purpose or Case Report: Leigh disease is a mitochondrial encephalopathy characterized by bilateral symmetric involvement of the brainstem and basal ganglia. SURF1 variants demonstrate restricted diffusion and symmetric T2/FLAIR hyperintensity of the substantia nigra, periaqueductal gray, and inferior olivary nuclei. MORC2 mutations, though primarily affecting the peripheral nervous system (causing Charcot–Marie–Tooth disease, spinal muscular atrophy–like features, and DIGFAN syndrome), can present with Leigh-like MRI patterns, leading to diagnostic uncertainty. Distinguishing these entities on MRI is essential for targeted genetic testing and counseling.
The purpose of this study is to compare MRI findings of a child with a confirmed MORC2 mutation to those of SURF1-variant Leigh disease, highlighting overlapping and distinguishing brainstem features that aid differential diagnosis.
Methods & Materials: Brain MRI sequences (T2-weighted, DWI, and ADC maps) were analyzed for a 2-year-old female with genetically confirmed MORC2 mutation and compared with SURF1-variant Leigh disease reference cases. Lesions were evaluated for symmetry, anatomic level, and diffusion behavior. Both supratentorial and infratentorial findings were assessed to identify imaging patterns distinguishing hypomyelination from mitochondrial energy failure.
Results: MORC2 mutation demonstrated supratentorial hypomyelination, asymmetric medullary signal, and facilitated diffusion in the substantia nigra and periaqueductal gray matter, findings atypical for Leigh disease. SURF1 cases showed symmetric T2 hyperintensity and restricted diffusion in the brainstem nuclei and cerebellar peduncles. Diffusion behavior and lesion symmetry differentiated the two entities.
Conclusions: MORC2-related neuroimaging changes can closely mimic SURF1-variant Leigh disease, but white-matter hypomyelination, asymmetry, and diffusivity changes distinguish them. Recognizing these patterns enhances diagnostic precision in pediatric neurogenetic disorders.