Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease that is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, infants with the severe form of the disease die before 2 years of age. SMARD1 is caused by mutations in the IGHMBP2 gene that determine a deficiency in the encoded IGHMBP2 protein, which plays a critical role in motor neuron survival because of its functions in mRNA processing and maturation. Although it is rare, SMARD1 is the second most common motor neuron disease of infancy, and currently, treatment is primarily supportive. No effective therapy is available for this devastating disease, although multidisciplinary care has been an essential element of the improved quality of life and life span extension in these patients in recent years. The objectives of this review are to discuss the current understanding of SMARD1 through a summary of the presently known information regarding its clinical presentation and pathogenesis and to discuss emerging therapeutic approaches. Advances in clinical care management have significantly extended the lives of individuals affected by SMARD1 and research into the molecular mechanisms that lead to the disease has identified potential strategies for intervention that target the underlying causes of SMARD1. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to halt or possibly prevent neurodegenerative disease in SMARD1 patients. The recent approval of the first gene therapy approach for SMA associated with mutations in the SMN1 gene may be a turning point for the application of this strategy for SMARD1 and other genetic neurological diseases.

脊髓性肌萎缩症 (SMA) 伴呼吸窘迫 1 型 (SMARD1) 是一种常染色体隐性遗传运动神经元疾病，其特征是远端和近端肌肉无力以及膈肌麻痹，导致呼吸窘迫。如果不进行干预，患有严重疾病的婴儿会在 2 岁之前死亡。 SMARD1 是由IGHMBP2基因突变引起的，该突变决定了所编码的 IGHMBP2 蛋白的缺陷，该蛋白由于其在 mRNA 加工和成熟中的功能，在运动神经元的存活中发挥着关键作用。尽管很少见，但 SMARD1 是婴儿期第二常见的运动神经元疾病，目前的治疗主要是支持性的。尽管近年来多学科护理已成为改善这些患者的生活质量和延长寿命的重要因素，但对于这种毁灭性的疾病尚无有效的治疗方法。本综述的目的是通过总结目前已知的有关 SMARD1 临床表现和发病机制的信息来讨论目前对 SMARD1 的理解，并讨论新兴的治疗方法。临床护理管理的进步显着延长了受 SMARD1 影响的个体的生命，并且对导致该疾病的分子机制的研究已经确定了针对 SMARD1 根本原因的潜在干预策略。通过基因替换或基因校正进行的基因治疗为变革性疗法提供了可能，以阻止或可能预防 SMARD1 患者的神经退行性疾病。 最近批准的第一个针对与SMN1基因突变相关的 SMA 的基因治疗方法可能是将该策略应用于 SMARD1 和其他遗传性神经系统疾病的转折点。