Hereditary myopathy with early respiratory failure

Hereditary myopathy with early respiratory failure (HMRF), also known as Edström myopathy or myosin storage myopathy with respiratory failure, is a rare inherited muscle disorder primarily caused by mutations in the TTN gene encoding the giant sarcomeric protein titin. The disease is characterized by progressive skeletal muscle weakness that notably involves the respiratory muscles at an early stage, often before limb weakness becomes severely disabling. This early respiratory involvement distinguishes HMRF from many other hereditary myopathies and can lead to respiratory insufficiency requiring ventilatory support. The condition typically presents in adulthood, most commonly between the third and fifth decades of life. Key clinical features include proximal and distal limb muscle weakness, with particular involvement of the lower limbs (especially the tibialis anterior and quadriceps muscles), neck flexor weakness, and progressive respiratory muscle weakness leading to nocturnal hypoventilation and eventual respiratory failure. Muscle biopsy characteristically shows cytoplasmic bodies and myofibrillar pathology. Some patients may also exhibit cardiac involvement, though this is less consistent. There is currently no curative treatment for HMRF. Management is supportive and multidisciplinary, focusing on monitoring and treating respiratory insufficiency with non-invasive ventilation (such as BiPAP), physical therapy to maintain mobility and muscle function, and cardiac surveillance when indicated. Early recognition of respiratory decline is critical, as timely initiation of ventilatory support can significantly improve quality of life and survival. Genetic counseling is recommended for affected families.

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