LMNA-Related Muscular Dystrophy with Clinical Intrafamilial Variability
The LMNA gene is associated to a huge broad of phenotypes, including congenital Emery-Dreifuss muscular dystrophy and late-onset LMNA-related muscular dystrophy. In these forms, muscle weakness, contractures, and cardiac impairment are common. In an autosomal dominant pedigree including 5 affected patients, NGS molecular analysis performed in 6 relatives identifies the heterozygous c.1129C>T p.Arg377Cys variant in the exon 6 of the LMNA gene in three of them. Clinical, laboratorial, imaging investigation of these affected patients showed a significant clinical variability: the father presented subclinical imaging muscular dystrophy masqueraded as radiculopathy. One of his sons presented cardiac arrhythmia, muscular weakness, elbow contractures, and intranuclear pseudoinclusions on muscle biopsy. A second son presented only decreased tendon reflexes. Two other brothers presenting myalgia and cramps were not carriers of the same mutation in the LMNA gene. Early diagnosis, considering these variable phenotype and genotype, is important for genetic counseling, as well as cardiac, and rehabilitation management.
KeywordsMuscular dystrophy LMNA Imaging Radiculopathy Electron microscopy Muscle biopsy
- LMNA gene
Lamin A/C gene
We would like to thank Cleides Campos de Oliveira and Simone Ferreira Inacio for technical assistance.
This work received financial support from the NGS Diagnostic Laboratory of the Human Genome Research Center and from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-CEPID), Conselho Nacional de Pesquisa (CNPq-INCT), and Financiadora de Projetos (FINEP) for the molecular studies.
Compliance with Ethical Standards
Ethical Publication Statement
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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