Dados do Trabalho

Título

Laminopathy presenting autophagic vacuolar histopathology.

RESUMO

Case report
A 17-year-old patient, with no consanguinity and normal motor development in childhood presented with difficulty in walking at the age 10, with gait on tiptoe. On examination, he had distal weakness MRC grade 3 for anterior tibialis and finger extensors and MRC 4 for gastrocnemius. Deep tendon reflexes were hypoactive and Achilles abolished. Contractures were observed in cervical, elbows and Achilles tendons, characterizing Emery-Dreifuss phenotype.
On investigation, we found elevated CK levels (1901 U/L). EMG showed myopathic changes on distal muscles. Muscle biopsy revealed dystrophic myopathic histological pattern and abundant rimmed vacuoles with autophagic characteristics. Additional evaluation revealed no cardiopathy nor respiratory damage. The whole-exome sequencing showed a likely pathogenic variant in LMNA (c.946A>C;p.Lys316Gln)
Discussion
Variants in heterozygosis in the LMNA can cause a wide spectrum of clinical manifestations known as laminopathy. There may be distal muscle weakness, with phenotype similar to Emery–Dreifuss muscular dystrophy, or due to peripheral nerve involvement, resembling Charcot-Marie-Tooth phenotype. Other patients present a congenital muscular dystrophy with severe axial involvement or, even, isolated cardiomyopathy. Described myopathological findings in skeletal muscle laminopathies typically manifest as nonspecific myopathic changes or dystrophic features.
Altered autophagy accompanied by rimmed vacuoles is a common denominator of many muscle diseases. When it is combined with protein aggregates the definition is of myofibrillar myopathy (MFM). Classical MFM pathology in skeletal muscle laminopathies has been reported in a few patients, however isolated autophagic vacuolar myopathy has not been described associated to LMNA. It was speculated that the mutated lamin A/C may disrupt nuclear lamina integrity, unanchor desmin from the nuclear envelope and cause disorganization of myofibrils linked to desmin. This process could lead to MFM pathology.
Conclusion
Vacuolar myopathies remain diagnostically challenging. Our case highlights the occurrence of this pathologic finding in patients with LMNA-related myopathy. We suggest including pathogenic variants in LMNA as a causative gene in the groups of vacuolar and myofibrillar myopathies. Identification of this condition means a high risk of ventricular arrhythmias in these patients and its importance is to prevent lethal cardiac events.

Palavras Chave

LMNA, vacuolar myopathies, miofibrillar myopathies