Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children
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 fib...
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doaj-28280d649a48460db92cd7f9728efcb12021-03-02T22:33:19ZengSAGE PublishingChild Neurology Open2329-048X2021-03-01810.1177/2329048X21991382Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in ChildrenSam Nicholas Russo MD0Amy Goldstein MD1Amel Karaa MD2Mary Kay Koenig MD3Melissa Walker MD, PhD4 Division of Child and Adolescent Neurology, Department of Pediatrics, The University of Texas McGovern Medical School, Houston, TX, USA Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Mitochondrial Disease Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA The University of Texas Mitochondrial Center of Excellence, Houston, TX, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAIn 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.https://doi.org/10.1177/2329048X21991382 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sam Nicholas Russo MD Amy Goldstein MD Amel Karaa MD Mary Kay Koenig MD Melissa Walker MD, PhD |
spellingShingle |
Sam Nicholas Russo MD Amy Goldstein MD Amel Karaa MD Mary Kay Koenig MD Melissa Walker MD, PhD Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children Child Neurology Open |
author_facet |
Sam Nicholas Russo MD Amy Goldstein MD Amel Karaa MD Mary Kay Koenig MD Melissa Walker MD, PhD |
author_sort |
Sam Nicholas Russo MD |
title |
Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children |
title_short |
Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children |
title_full |
Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children |
title_fullStr |
Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children |
title_full_unstemmed |
Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A>G Variant in Children |
title_sort |
leigh syndrome as a phenotype of near-homoplasmic m.8344 a>g variant in children |
publisher |
SAGE Publishing |
series |
Child Neurology Open |
issn |
2329-048X |
publishDate |
2021-03-01 |
description |
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. |
url |
https://doi.org/10.1177/2329048X21991382 |
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