Qualitative or quantitative defects of selenoprotein N1

Qualitative or quantitative defects of selenoprotein N1 (SELENON, formerly SEPN1) refer to a group of neuromuscular disorders caused by mutations in the SELENON gene (previously known as SEPN1), which encodes selenoprotein N, a protein involved in oxidative stress protection and calcium homeostasis in muscle cells. These defects underlie several overlapping clinical entities historically described as SEPN1-related myopathy, including rigid spine muscular dystrophy (RSMD1), multiminicore disease (classical form), desmin-related myopathy with Mallory body-like inclusions, and congenital fiber-type disproportion. The condition primarily affects skeletal muscles and the respiratory system. Key clinical features include early-onset axial muscle weakness, progressive rigidity of the spine (particularly the cervical and thoracic segments), scoliosis, and early and severe respiratory insufficiency that is often disproportionate to the degree of limb weakness. Affected individuals typically present in infancy or early childhood with poor head control, hypotonia, and delayed motor milestones. Limb weakness tends to be mild to moderate, and many patients retain the ability to walk. However, nocturnal hypoventilation and restrictive lung disease are major concerns and frequently require non-invasive ventilatory support. Feeding difficulties and failure to thrive may also occur in early life. There is currently no curative treatment for SELENON-related myopathies. Management is supportive and multidisciplinary, focusing on respiratory monitoring and ventilatory support (often nocturnal non-invasive ventilation), orthopedic management of spinal rigidity and scoliosis, physical therapy to maintain mobility and prevent contractures, and nutritional support when needed. Early recognition of respiratory compromise is critical, as it is the primary determinant of morbidity and mortality. Genetic counseling is recommended for affected families.

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