Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy - a Genotype/Phenotype Correlation

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2023 May 14

PMID 37182895

Authors

Clara Gontijo Camelo

Mariana Cunha Artilheiro

Cristiane Araujo Martins Moreno

Suely Fazio Ferraciolli

Andre Macedo Serafim Silva

Tatiana Ribeiro Fernandes

Leandro Tavares Lucato

Antonio Jose Rocha

Umbertina Conti Reed

Edmar Zanoteli

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy.

Enzmann C, Steiner L, Pospieszny K, Zweier C, Plattner K, Baumann D J Neuromuscul Dis. 2024; 11(5):1021-1033.

PMID: 39213089 PMC: 11380305. DOI: 10.3233/JND-240023.

Exploring Splice-Site Mutations in LAMA2-Related Muscular Dystrophies: A Comprehensive Analysis of Genotypic and Phenotypic Patterns.

Nmer S, Ameli A, Trhanint S, Chaouki S, Bouguenouch L, Ouldim K Cureus. 2024; 16(6):e61599.

PMID: 38962616 PMC: 11221619. DOI: 10.7759/cureus.61599.

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