COGNITIVE PROFILES AND THEIR ASSOCIATION WITH BRAIN ABNORMALITIES, EPILEPSY, AND GENETICS IN CHILDREN, ADOLESCENTS, AND ADULTS WITH LAMA2-ASSOCIATED MUSCULAR DYSTROPHY (LAMA2-RD)

LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive congenital muscular dystrophy caused by mutations in the LAMA2 gene, which encodes laminin α2 (merosin), a key protein stabilizing muscle fibers. Around 60–80% of cases involve single nucleotide variants, while 20–40% have exon deletions. Laminin-211 is also expressed in the brain, and its deficiency can disrupt neuronal migration, leading to cortical malformations and white matter changes.
About 10–30% of patients develop epilepsy with variable seizure types, sometimes associated with cognitive decline. Case reports indicate that cognitive abilities in patients with LAMA2-RD range widely, and some show attention and executive function problems even with an IQ within normal range.
However, cognitive function in LAMA2-RD remains poorly studied, with limited data linking cognitive outcomes to brain malformations, epilepsy, and genetics. Often only screening tests have been used to diagnose intellectual disabilities and measure cognitive abilities, which should be done by standardized neuropsychological assessments. The current project therefore aims to better characterize IQ and other cognitive domains (attention, visuospatial skills, EF and memory) in these patients using neuropsychological assessments and determine factors that influence them. A better understanding of the cognitive profile and its determinants in LAMA2-RD may have important implications for clinical management, educational support, and prognosis, as well as for patient stratification and outcome selection in future clinical trials. The study is ongoing and preliminary results will be presented.