Sleep phenotypes and respiratory disturbances in spinal muscular atrophy: A systematic review of clinical evidence

Background 5q Spinal Muscular Atrophy (SMA) is a rare neuromuscular disorder in which sleep-related respiratory disturbances are common and may worsen morbidity and quality of life. However, systematic evidence on sleep architecture, sleep-disordered breathing (SDB), and treatment outcomes in SMA is limited. Objective To provide a comprehensive synthesis of the existing evidence on sleep characteristics, respiratory disturbances, and the impact of non-invasive ventilation (NIV) in patient with 5q-SMA treated with disease-modifying therapied (DMTs) across lifespan. Methods A systematic literature search identified 233 records, of which 20 studies met inclusion criteria. Data were extracted regarding study design, SMA phenotype, sleep assessment, apnea type, apnea–hypopnea index (AHI), oxygen saturation, sleep architecture, and clinical outcomes. Results Twenty studies (ranging from single case reports to cohorts of >100 patients) revealed that SDB, particularly obstructive and central apneas, is highly prevalent in SMA types 1–3. Sleep architecture abnormalities include reduced REM sleep, increased N1, and abnormal cyclic alternating pattern (CAP) indices, suggesting impaired arousability. Nocturnal hypoventilation may occur even without overt hypoxemia. Interventions with NIV consistently reduced AHI and improved nocturnal oxygenation. DMTs showed potential benefits in stabilizing or improving sleep outcomes, though residual SDB remains common. Conclusions Sleep disturbances in SMA are multifactorial, reflecting both respiratory muscle weakness and central nervous system involvement. NIV remains essential in managing SDB, while DMTs hold promise for improving long-term outcomes. Regular polysomnography and respiratory assessments are recommended in the follow-up of all type of SMA patients.