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Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature

Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal p...

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Autores principales: Frongia, Ivana, Rizzi, Susanna, Baga, Margherita, Ceteroni, Laura Maria, Spagnoli, Carlotta, Salerno, Grazia Gabriella, Frattini, Daniele, Kaare, Milja, Pisani, Francesco, Fusco, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493287/
https://www.ncbi.nlm.nih.gov/pubmed/34630290
http://dx.doi.org/10.3389/fneur.2021.718808
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author Frongia, Ivana
Rizzi, Susanna
Baga, Margherita
Ceteroni, Laura Maria
Spagnoli, Carlotta
Salerno, Grazia Gabriella
Frattini, Daniele
Kaare, Milja
Pisani, Francesco
Fusco, Carlo
author_facet Frongia, Ivana
Rizzi, Susanna
Baga, Margherita
Ceteroni, Laura Maria
Spagnoli, Carlotta
Salerno, Grazia Gabriella
Frattini, Daniele
Kaare, Milja
Pisani, Francesco
Fusco, Carlo
author_sort Frongia, Ivana
collection PubMed
description Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported. Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A>G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders. Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype–phenotype correlation.
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spelling pubmed-84932872021-10-07 Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature Frongia, Ivana Rizzi, Susanna Baga, Margherita Ceteroni, Laura Maria Spagnoli, Carlotta Salerno, Grazia Gabriella Frattini, Daniele Kaare, Milja Pisani, Francesco Fusco, Carlo Front Neurol Neurology Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported. Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A>G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders. Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype–phenotype correlation. Frontiers Media S.A. 2021-09-22 /pmc/articles/PMC8493287/ /pubmed/34630290 http://dx.doi.org/10.3389/fneur.2021.718808 Text en Copyright © 2021 Frongia, Rizzi, Baga, Ceteroni, Spagnoli, Salerno, Frattini, Kaare, Pisani and Fusco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Frongia, Ivana
Rizzi, Susanna
Baga, Margherita
Ceteroni, Laura Maria
Spagnoli, Carlotta
Salerno, Grazia Gabriella
Frattini, Daniele
Kaare, Milja
Pisani, Francesco
Fusco, Carlo
Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title_full Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title_fullStr Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title_full_unstemmed Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title_short Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
title_sort infantile-onset charcot–marie–tooth disease with pyramidal features and white matter abnormalities due to a de novo morc2 gene variant: a case report and brief review of the literature
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493287/
https://www.ncbi.nlm.nih.gov/pubmed/34630290
http://dx.doi.org/10.3389/fneur.2021.718808
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