Merosin-Deficient Congenital Muscular Dystrophy (MDCMD): A Case Report with MRI, MRS and DTI Findings

Ip, Janice; Hui, Peter Kei Tat; Chau, MT; Lam, Wendy

doi:10.3941/jrcr.v6i8.997

Cited by 4 publications

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“…Examples exist of the possible double involvement of brain and muscle in neuromuscular diseases, demonstrated as white matter abnormalities by DWI tractography. In particular, alterations of white matter projection, association and commissural fibres have been described in myotonic dystrophy type 1 [43][44][45] and alterations of diffusion coefficient of white matter have been revealed for merosin-deficient congenital muscular dystrophy [46,47].…”

Section: Introductionmentioning

confidence: 99%

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging

et al. 2021

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Introduction Cognitive difficulties and neuropsychological alterations in Duchenne and Becker muscular dystrophy (DMD, BMD) boys are not yet sufficiently explored, although this topic could have a relevant impact, finding novel biomarkers of disease both at genetics and neuroimaging point of view. The current study aims to: 1) analyze the neuropsychological profile of a group of DMD and BMD boys without cognitive impairment with an assessment of their executive functions; 2) explore the structural connectivity in DMD, BMD, and age-matched controls focusing on cortico-subcortical tracts that connect frontal cortex, basal ganglia, and cerebellum via the thalamus; 3) explore possible correlations between altered structural connectivity and clinical neuropsychological measures. Materials and methods This pilot study included 15 boys (5 DMD subjects, 5 BMD subjects, and 5 age-matched typically developing, TD). They were assessed using a neuropsychological assessment protocol including cognitive and executive functioning assessment and performed a 1.5T MRI brain exam including advance Diffusion Weighted Imaging (DWI) method for tractography. Structural connectivity measurements were extracted along three specific tracts: Cortico-Ponto-Cerebellar Tract (CPCT), Cerebellar-Thalamic Tract (CTT), and Superior Longitudinal Fasciculus (SLF). Cortical-Spinal Tract (CST) was selected for reference, as control tract. Results Regarding intellectual functioning, a major impairment in executive functions compared to the general intellectual functioning was observed both for DMD (mean score = 86.20; SD = 11.54) and for BMD children (mean score = 88; SD = 3.67). Mean FA resulted tendentially always lower in DMD compared to both BMD and TD groups for all the examined tracts. The differences in FA were statistically significant for the right CTT (DMD vs BMD, p = 0.002, and DMD vs TD, p = 0.0015) and the right CPCT (DMD vs TD, p = 0.008). Concerning DMD, significant correlations emerged between FA-R-CTT and intellectual quotients (FIQ, p = 0.044; ρs = 0.821), and executive functions (Denomination Total, p = 0.044, ρs = 0.821; Inhibition Total, p = 0.019, ρs = 0.900). BMD showed a significant correlation between FA-R-CPCT and working memory index (p = 0.007; ρs = 0.949). Discussion and conclusion In this pilot study, despite the limitation of sample size, the findings support the hypothesis of the involvement of a cerebellar-thalamo-cortical loop for the neuropsychological profile of DMD, as the CTT and the CPCT are involved in the network and the related brain structures are known to be implied in executive functions. Our results suggest that altered WM connectivity and reduced fibre organization in cerebellar tracts, probably due to the lack of dystrophin in the brain, may render less efficient some neuropsychological functions in children affected by dystrophinopathies. The wider multicentric study could help to better establish the role of cerebellar connectivity in neuropsychological profile for dystrophinopathies, identifying possible novel diagnostic and prognostic biomarkers.

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Section: Introductionmentioning

confidence: 99%

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging

et al. 2021

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“…The G domain at the C terminus of merosin (exons 46–64) is responsible in the connection between the dystrophin‐glycoprotein and the extracellular matrix 24 . Deficiency of this domain disrupts the link between subsarcolemmal cytoskeleton and extracellular matrix, which causes muscle degeneration 1 …”

Section: Discussionmentioning

confidence: 99%

“…The merosin‐deficient congenital muscular dystrophy type 1A (MDC1A) with autosomal recessive inheritance affects the peripheral and central nervous system in children 1 2,3 …”

Section: Introductionmentioning

confidence: 99%

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Khorrami

Goleij

Karamad

et al. 2021

Clinical Laboratory Analysis

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Background Merosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES). Methods In the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants. Results We identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis. Conclusions In general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.

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“…However, FA is used as a readout for white matter maturation, as the typical time course in both mice (Mori and Zhang, 2006 ) and humans (Keunen et al, 2018 ) demonstrates that during the perinatal period FA increases in white matter tracts as resident axons become increasingly myelinated. In one case report of a 6-year-old MDC1A patient with gross developmental delay, along with typical diffuse white matter hyperintensities on T2 weighted MRI, diffusion tensor imaging (DTI) revealed a reduced FA (Ip et al, 2012 ).…”

Section: Central Nervous System Involvement In Mdc1amentioning

confidence: 99%

Brain Dysfunction in LAMA2-Related Congenital Muscular Dystrophy: Lessons From Human Case Reports and Mouse Models

Arreguin

Colognato

2020

Front. Mol. Neurosci.

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Laminin α2 gene (LAMA2)-related Congenital Muscular Dystrophy (CMD) was distinguished by a defining central nervous system (CNS) abnormality-aberrant white matter signals by MRI-when first described in the 1990s. In the past 25 years, researchers and clinicians have expanded our knowledge of brain involvement in LAMA2-related CMD, also known as Congenital Muscular Dystrophy Type 1A (MDC1A). Neurological changes in MDC1A can be structural, including lissencephaly and agyria, as well as functional, including epilepsy and intellectual disability. Mouse models of MDC1A include both spontaneous and targeted LAMA2 mutations and range from a partial loss of LAMA2 function (e.g., dy 2J /dy 2J), to a complete loss of LAMA2 expression (dy 3K /dy 3K). Diverse cellular and molecular changes have been reported in the brains of MDC1A mouse models, including blood-brain barrier dysfunction, altered neuro-and gliogenesis, changes in synaptic plasticity, and decreased myelination, providing mechanistic insight into potential neurological dysfunction in MDC1A. In this review article, we discuss selected studies that illustrate the potential scope and complexity of disturbances in brain development in MDC1A, and as well as highlight mechanistic insights that are emerging from mouse models.

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Merosin-Deficient Congenital Muscular Dystrophy (MDCMD): A Case Report with MRI, MRS and DTI Findings

Cited by 4 publications

References 0 publications

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Brain Dysfunction in LAMA2-Related Congenital Muscular Dystrophy: Lessons From Human Case Reports and Mouse Models

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