LMOD2-related dilated cardiomyopathy presenting in late infancy

Area of Science:

• Cardiovascular Biology
• Genetics
• Muscle Physiology

Background:

• Leiomodin-2 (LMOD2) is crucial for regulating thin filament length in muscle, primarily through actin polymerization.
• Lmod2 deficiency in mice leads to dilated cardiomyopathy (DCM) and premature death due to impaired cardiac contractility from shortened thin filaments.
• Previously, biallelic LMOD2 variants causing perinatal onset DCM were reported in three infants from two families.

Observation:

• This report details a third family with a child diagnosed with DCM at nine months of age.
• The affected child presented with a previously identified homozygous frameshift variant (c.1243_1244delCT, p.L415Vfs*108) in the LMOD2 gene.
• A relevant family history included a sibling who died at one year of age with cardiomegaly.

Findings:

• The study expands the clinical spectrum of LMOD2-related cardiomyopathy, demonstrating a later infantile presentation.
• The findings confirm the homozygous frameshift variant's association with DCM and highlight potential autosomal recessive inheritance.
• This case underscores the impact of LMOD2 variants on cardiac structure and function, even with later onset.

Implications:

• LMOD2-related cardiomyopathy is a rare but significant cause of inherited cardiomyopathy linked to thin filament dysregulation.
• Genetic evaluation for LMOD2 variants should be considered in infants with early-onset cardiomyopathy, particularly those with suspected autosomal recessive inheritance.
• Early diagnosis and understanding of LMOD2's role can inform genetic counseling and potential therapeutic strategies for affected individuals.