Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
BMC Neurol. 2024 Oct 23;24(1):409. doi: 10.1186/s12883-024-03852-4.
SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG).
The Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient's age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed.
This study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines.
This study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee ('METC Oost-Nederland'; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland , file number: 2023-16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15).
SELENON 相关肌病（SELENON-RM）是一种罕见的先天性肌病，其特征为进行性轴性肌无力、脊柱僵硬、脊柱侧凸和呼吸功能不全。层粘连蛋白-α2 相关肌病（LAMA2-MD）具有相似的临床表型，范围从严重的早发性先天性肌营养不良 1A 型（MDC1A）到较轻的形式，表现为儿童或成年起病的肢带型肌营养不良。最初的 1.5 年自然病史随访显示，90%的患者骨质量较低，所有 SELENON-RM 和大多数 LAMA2-MD 患者均存在呼吸功能损害，许多患者存在心脏危险因素。然而，为了达到试验准备阶段，还需要进一步广泛了解长期自然病史数据以及临床和功能结局指标。因此，我们通过 3 年和 5 年的随访（扩展 LAST STRONG）扩展了自然病史研究。
扩展 LAST STRONG 是一项针对所有年龄的经基因证实的 SELENON-RM 或 LAMA2-MD 患者的荷兰语自然病史长期研究，于 2023 年 9 月开始。患者在 2 年内两次到我院就诊，以完成最初 LAST-STRONG 研究的 5 年随访。在两次就诊时，他们接受标准化的神经系统检查、手持式测力计（年龄≥5 岁）、功能测量、肌肉超声、呼吸评估（肺活量测定、最大吸气和呼气压力、嗅探鼻吸气压力；年龄≥5 岁）、双能 X 射线吸收法（DEXA）扫描（年龄≥2 岁）、左手 X 射线（年龄≤17 岁）、下肢 MRI（年龄≥10 岁）、8 天加速度计（年龄≥2 岁）和问卷调查（患者报告和/或家长代理；年龄≥2 岁）。所有检查均根据患者的年龄和功能能力进行调整。将评估所有后续就诊之间的疾病进展情况以及结局指标之间的关系。
本研究将为 SELENON-RM 和 LAMA2-MD 患者的 5 年自然病史提供有价值的见解，并有助于进一步选择相关和敏感的临床和功能结局指标。此外，该数据将有助于优化临床护理中的自然病史数据收集，并有助于制定临床护理指南。
本研究方案（包括患者信息和同意书）已获得医学伦理审查委员会（'METC Oost-Nederland'；https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland，注册号：2023-16401）的批准。该研究已在 ClinicalTrials.gov 注册（NCT06132750；研究注册日期：2023-10-05；研究首次通过日期：2023-11-15）。
