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Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation
BACKGROUND: LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and varies in severity, from a severe, congenital type to a milder, late-onset form. However, the disease does not only affect the muscles, but has systemic involvement and can lead to alterations such as brain ma...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357150/ https://www.ncbi.nlm.nih.gov/pubmed/37182895 http://dx.doi.org/10.3233/JND-221638 |
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author | Camelo, Clara Gontijo Artilheiro, Mariana Cunha Martins Moreno, Cristiane Araújo Ferraciolli, Suely Fazio Serafim Silva, André Macedo Fernandes, Tatiana Ribeiro Lucato, Leandro Tavares Rocha, Antônio José Reed, Umbertina Conti Zanoteli, Edmar |
author_facet | Camelo, Clara Gontijo Artilheiro, Mariana Cunha Martins Moreno, Cristiane Araújo Ferraciolli, Suely Fazio Serafim Silva, André Macedo Fernandes, Tatiana Ribeiro Lucato, Leandro Tavares Rocha, Antônio José Reed, Umbertina Conti Zanoteli, Edmar |
author_sort | Camelo, Clara Gontijo |
collection | PubMed |
description | BACKGROUND: LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and varies in severity, from a severe, congenital type to a milder, late-onset form. However, the disease does not only affect the muscles, but has systemic involvement and can lead to alterations such as brain malformation, epilepsy and intellectual disability. OBJECTIVE: Describe the frequency of cortical malformations, epilepsy and intellectual disability in LAMA2-RD in a Brazilian cohort and correlate the neurological findings to genetic and motor function. METHODS: This is an observational study of 52 LAMA2-RD patients, who were divided into motor function subgroups and compared based on brain MRI findings, epilepsy, intellectual disability, and type of variants and variant domains. RESULTS: 44 patients (84.6%) were only able to sit, and 8 patients (15.4%) were able to walk. 10 patients (19.2%) presented with cortical malformations (polymicrogyria, lissencephaly-pachygyria, and cobblestone),10 patients (19.2%) presented with epilepsy, and 8 (15.4%) had intellectual disability. CNS manifestations correlated with a more severe motor phenotype and none of the patients able to walk presented with cortical malformation or epilepsy. There was a relation between gene variants affecting the laminin-α2 LG-domain and the presence of brain malformation (P = 0.016). There was also a relation between the presence of null variants and central nervous system involvement. A new brazilian possible founder variant was found in 11 patients (21,15%) (c.1255del; p. Ile419Leufs(*)4). CONCLUSION: Cortical malformations, epilepsy and intellectual disability are more frequent among LAMA2-RD patients than previously reported and correlate with motor function severity and the presence of variants affecting the laminin-α2 LG domain. This brings more insight fore phenotype-genotype correlations, shows the importance of reviewing the brain MRI of patients with LAMA2-RD and allows greater attention to the risk of brain malformation, epilepsy, and intellectual disability in those patients with variants that affect the LG domain. |
format | Online Article Text |
id | pubmed-10357150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103571502023-07-21 Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation Camelo, Clara Gontijo Artilheiro, Mariana Cunha Martins Moreno, Cristiane Araújo Ferraciolli, Suely Fazio Serafim Silva, André Macedo Fernandes, Tatiana Ribeiro Lucato, Leandro Tavares Rocha, Antônio José Reed, Umbertina Conti Zanoteli, Edmar J Neuromuscul Dis Research Article BACKGROUND: LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and varies in severity, from a severe, congenital type to a milder, late-onset form. However, the disease does not only affect the muscles, but has systemic involvement and can lead to alterations such as brain malformation, epilepsy and intellectual disability. OBJECTIVE: Describe the frequency of cortical malformations, epilepsy and intellectual disability in LAMA2-RD in a Brazilian cohort and correlate the neurological findings to genetic and motor function. METHODS: This is an observational study of 52 LAMA2-RD patients, who were divided into motor function subgroups and compared based on brain MRI findings, epilepsy, intellectual disability, and type of variants and variant domains. RESULTS: 44 patients (84.6%) were only able to sit, and 8 patients (15.4%) were able to walk. 10 patients (19.2%) presented with cortical malformations (polymicrogyria, lissencephaly-pachygyria, and cobblestone),10 patients (19.2%) presented with epilepsy, and 8 (15.4%) had intellectual disability. CNS manifestations correlated with a more severe motor phenotype and none of the patients able to walk presented with cortical malformation or epilepsy. There was a relation between gene variants affecting the laminin-α2 LG-domain and the presence of brain malformation (P = 0.016). There was also a relation between the presence of null variants and central nervous system involvement. A new brazilian possible founder variant was found in 11 patients (21,15%) (c.1255del; p. Ile419Leufs(*)4). CONCLUSION: Cortical malformations, epilepsy and intellectual disability are more frequent among LAMA2-RD patients than previously reported and correlate with motor function severity and the presence of variants affecting the laminin-α2 LG domain. This brings more insight fore phenotype-genotype correlations, shows the importance of reviewing the brain MRI of patients with LAMA2-RD and allows greater attention to the risk of brain malformation, epilepsy, and intellectual disability in those patients with variants that affect the LG domain. IOS Press 2023-07-04 /pmc/articles/PMC10357150/ /pubmed/37182895 http://dx.doi.org/10.3233/JND-221638 Text en © 2023 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Camelo, Clara Gontijo Artilheiro, Mariana Cunha Martins Moreno, Cristiane Araújo Ferraciolli, Suely Fazio Serafim Silva, André Macedo Fernandes, Tatiana Ribeiro Lucato, Leandro Tavares Rocha, Antônio José Reed, Umbertina Conti Zanoteli, Edmar Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title | Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title_full | Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title_fullStr | Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title_full_unstemmed | Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title_short | Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation |
title_sort | brain mri abnormalities, epilepsy and intellectual disability in lama2 related dystrophy – a genotype/phenotype correlation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357150/ https://www.ncbi.nlm.nih.gov/pubmed/37182895 http://dx.doi.org/10.3233/JND-221638 |
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