Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children

• Main Authors: Sam Nicholas Russo MD, Amy Goldstein MD, Amel Karaa MD, Mary Kay Koenig MD, Melissa Walker MD, PhD
• Format: Article
• Language: English
• Published: SAGE Publishing 2021-03-01
• Series: Child Neurology Open
• Online Access: https://doi.org/10.1177/2329048X21991382

In the field of mitochondrial medicine, correlation of clinical phenotype with mutation heteroplasmy remains an outstanding question with few, if any, clear thresholds corresponding to a given phenotype. The m.8344A>G mutation is most commonly associated with myoclonus epilepsy and ragged red fiber syndrome (MERRF) at varying levels of heteroplasmy. However, a handful of cases been previously reported in which individuals homoplasmic or nearly homoplasmic for this mutation in the blood have presented with multiple bulbar palsies, respiratory failure, and progressive neurologic decline almost uniformly following a respiratory illness. MRI brain in all affected individuals revealed symmetric T2 hyperintense lesions of subcortical gray matter structures, consistent with Leigh syndrome. Here, we present 3 cases with clinical, biochemical, and neuro-imaging findings with the additional reporting of spinal lesions. This new phenotype supports a heteroplasmy-dependent phenotype model for this mutation and recognition of this can help clinicians with diagnosis and anticipatory clinical guidance.