Epilepsy in LAMA2-related muscular dystrophy: A systematic review of the literature

Salvati, Andrea; Bonaventura, Eleonora; Sesso, Gianluca; Pasquariello, Rossella; Sicca, Federico

doi:10.1016/j.seizure.2021.07.020

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…Variants in LAMA1 cause Poretti–Boltshauser syndrome (OMIM #615960), characterized by delayed motor development, speech delay, and cognitive function; and seizures, tics, and spasticity have also been observed ( Aldinger et al, 2014 ; Elmas et al, 2020 ). LAMA2 is the causative gene of autosomal recessive limb-girdle muscular dystrophy-23 (OMIM #618138) and congenital merosin deficient or partially deficient muscular dystrophy (OMIM #607855), in which epilepsy was regarded as one of the core features ( Chan et al, 2014 ; Xiong et al, 2015 ; Salvati et al, 2021 ). The LAMA3 gene is the responsible gene of Herlitz type junctional epidermolysis bullosa (OMIM #226700), generalized atrophic benign epidermolysis bullosa (OMIM #226650), and laryngo-onycho-cutaneous syndrome (OMIM #245660) ( Kivirikko et al, 1995 ; McGrath et al, 1995 ; Vidal et al, 1995 ; Nakano et al, 2002 ; McLean et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

Recessive LAMA5 Variants Associated With Partial Epilepsy and Spasms in Infancy

Luo

Liu

Wang

et al. 2022

Front. Mol. Neurosci.

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ObjectiveThe LAMA5 gene encodes the laminin subunit α5, the most abundant laminin α subunit in the human brain. It forms heterotrimers with the subunit β1/β2 and γ1/γ3 and regulates neurodevelopmental processes. Genes encoding subunits of the laminin heterotrimers containing subunit α5 have been reported to be associated with human diseases. Among LAMAs encoding the laminin α subunit, LAMA1-4 have also been reported to be associated with human disease. In this study, we investigated the association between LAMA5 and epilepsy.MethodsTrios-based whole-exome sequencing was performed in a cohort of 118 infants suffering from focal seizures with or without spasms. Protein modeling was used to assess the damaging effects of variations. The LAMAs expression was analyzed with data from the GTEX and VarCards databases.ResultsSix pairs of compound heterozygous missense variants in LAMA5 were identified in six unrelated patients. All affected individuals suffered from focal seizures with mild developmental delay, and three patients presented also spasms. These variants had no or low allele frequencies in controls and presented statistically higher frequency in the case cohort than in controls. The recessive burden analysis showed that recessive LAMA5 variants identified in this cohort were significantly more than the expected number in the East Asian population. Protein modeling showed that at least one variant in each pair of biallelic variants affected hydrogen bonds with surrounding amino acids. Among the biallelic variants in cases with only focal seizures, two variants of each pair were located in different structural domains or domains/links, whereas in the cases with spasms, the biallelic variants were constituted by two variants in the identical functional domains or both with hydrogen bond changes.ConclusionRecessive LAMA5 variants were potentially associated with infant epilepsy. The establishment of the association between LAMA5 and epilepsy will facilitate the genetic diagnosis and management in patients with infant epilepsy.

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Section: Discussionmentioning

confidence: 99%

Recessive LAMA5 Variants Associated With Partial Epilepsy and Spasms in Infancy

Luo

Liu

Wang

et al. 2022

Front. Mol. Neurosci.

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“…These larger cohorts lead to a much better genotype–phenotype characterization of these syndromes. In the past 2 years, several single-center and multicentric studies have generated new insights into the electrographic and phenotypic spectrum of the following genetic epilepsies: PIGS-associated early-onset developmental and epileptic encephalopathy [6], Angelman syndrome [7], LAMA-2 -related muscular dystrophy [8], Mowat–Wilson syndrome [9], neurofibromatosis type 1 [10], CLCN4 -related epilepsy [11], Poirier–Bienvenu syndrome [12], and familial cortical myoclonic tremor with epilepsy type 1 [13].…”

Section: Genotype–phenotype Correlationmentioning

confidence: 99%

Updates on the diagnostic evaluation, genotype–phenotype correlation, and treatments of genetic epilepsies

Zimmern

Korff

2022

Current Opinion in Pediatrics

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Purpose of reviewThis article reviews the latest publications in genetic epilepsies, with an eye on publications that have had a translational impact. This review is both timely and relevant as translational discoveries in genetic epilepsies are becoming so frequent that it is difficult for the general pediatrician and even the general child neurologist to keep up.Recent findingsWe divide these publications from 2021 and 2022 into three categories: diagnostic testing, genotype–phenotype correlation, and therapies. We also summarize ongoing and upcoming clinical trials.SummaryTwo meta-analyses and systematic reviews suggest that exome and genome sequencing offer higher diagnostic yield than gene panels. Genotype–phenotype correlation studies continue to increase our knowledge of the clinical evolution of genetic epilepsy syndromes, particularly with regards to sudden death, auditory dysfunction, neonatal presentation, and magnetoencephalographic manifestations. Pyridoxine supplementation may be helpful in seizure management for various genetic epilepsies. There has been interest in using the neurosteroid ganaxolone for various genetic epilepsy syndromes, with clear efficacy in certain trials. Triheptanoin for epilepsy secondary to glucose transporter 1 (GLUT1) deficiency syndrome is not clearly effective but further studies will be needed.

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“…The occurrence of cortical malformations was not associated with an earlier epilepsy onset. The electrophysiological and neurodevelopmental features are unclear, however epileptic seizures may be one of the core features of LAMA2-MD [4] . SELENON-RM patients were reported to exhibit a remarkably consistent and recognizable phenotype.…”

Section: Introductionmentioning

confidence: 99%