LAMA2 variants associated with muscular dystrophy, brain structural abnormalities, and epilepsy: a genotype-phenotype...

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• LAMA2-related congenital muscular dystrophy (LAMA2-MD) is a complex genetic disorder.
• It is characterized by progressive muscle weakness, brain abnormalities, epilepsy, and multisystem involvement.

Purpose of the Study:

• To characterize the clinical features of LAMA2-MD.
• To understand the temporal progression of the disease.
• To establish genotype-phenotype correlations in LAMA2-MD.

Main Methods:

• Retrospective analysis of medical records from genetically confirmed LAMA2-MD patients.
• Systematic review of clinical manifestations, laboratory findings, and neuroimaging.
• Comprehensive genetic analyses including variant data retrieval from public databases.

Main Results:

• Five patients (2 males, 3 females) were studied, presenting with delayed motor milestones and persistent motor impairment.
• Elevated creatine kinase (CK) levels and symmetrical white matter abnormalities on MRI were observed.
• All patients had compound heterozygous variants in the LAMA2 gene, with stop-gain variants linked to MDC1A and missense variants to late-onset limb-girdle muscular dystrophy.

Conclusions:

• LAMA2-MD displays a wide spectrum of phenotypes and a progressive course.
• Early signs include muscle weakness, developmental delays, contractures, seizures, and intracranial abnormalities.