LMNA-Related Muscular Dystrophy with Clinical Intrafamilial Variability

Area of Science:

• Genetics
• Neurology
• Cardiology

Background:

• The LMNA gene mutations are linked to diverse muscular dystrophies, including Emery-Dreifuss muscular dystrophy and late-onset forms.
• These conditions often manifest with muscle weakness, contractures, and cardiac issues.

Observation:

• A heterozygous c.1129C>T p.Arg377Cys variant in exon 6 of the LMNA gene was identified in three affected individuals within an autosomal dominant family.
• Clinical presentations varied significantly, ranging from subclinical imaging findings to cardiac arrhythmias, muscle weakness, contractures, and muscle biopsy pseudoinclusions.

Findings:

• The identified LMNA variant exhibited variable expressivity and incomplete penetrance, as evidenced by differing clinical severity among affected family members.
• Two brothers with myalgia and cramps were negative for the LMNA mutation, highlighting the complexity of genotype-phenotype correlations.

Implications:

• Early and accurate diagnosis of LMNA-related muscular dystrophy is essential for effective genetic counseling.
• Proactive cardiac monitoring and tailored rehabilitation strategies are critical for managing patients with this condition.