Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disorder. It occurs in almost 1 in 11,000 live births and is caused by mutations in the survival motor neuron (SMN) 1 gene. SMN protein is crucial for the proper functioning of motor neurons and its reduced levels cause progressive muscle weakness.
The severity of SMA varies in patients due to the copy number of a homologous SMN2 gene. Previously, children with SMA type 1 suffered from progressive weakness of muscles with palliative treatment being the only management and a median survival age as young as 13.5 months. However, disease-modifying treatments (DMTs) such as nusinersen, completely changed the children’s history and made the prognosis for type 1 SMA clinically treatable.
This retrospective national observational study assessed the effect of nusinersen on the management and outcomes of patients with type 1 SMA in the UK. This study included SMA patients with confirmed SMN1 gene mutations and a clinical diagnosis of type 1 SMA which was registered as the service evaluation under Great Ormond Street Hospital.
SMA-REACH UK is a network of 17 pediatric neuromuscular centers in the UK to standardize clinical and physiotherapy assessments in SMA patients. This analysis was done for patients by looking into subtypes of SMA, SMN2 copy number, age at first dose of nusinersen, motor functions, seating type, sitting ability, and respiratory support.
Spinal posture and asymmetry were given specific attention with scoliosis, kyphosis, and neck range of motion being part of routine physiotherapy reviews, and X-rays were indicated for spinal asymmetry. Each center took information on spinal care including the use of spinal jackets and thoraco-lumbar-sacral orthoses (TLSO).
A UK-wide study across 13 neuromuscular centers collected the data on 80 out of 101 (79%) Type 1 SMA patients from Northern Ireland, Scotland, Wales, and England. Out of 80 children, 33 had both spinal asymmetry and kyphosis, 26 had spinal asymmetry alone, 6 had kyphosis alone, and 14 showed no spinal abnormalities.
Among the 20 children with no spinal asymmetry (kyphosis-only cases included), the age range was from 4 months to 8.6 years with a median age of 3.8 years. The distribution of the participants in the study was 60% type 1b and 40% type 1c where no type 1a was reported.
Of the participants, 33 children (41%) had limited neck mobility. One child also had plagiocephaly and 5 presented with torticollis. There was only one case of plagiocephaly with no limitation in neck mobility. Of the children with limited motion of the neck, 26 of 33 (79%) had spinal asymmetry.
Additionally, 35 children (44%) had a full range of neck motion, whereas the documentation is unavailable for 12 children (15%). The study draws attention to a major shift in the natural history of type 1 SMA after the introduction of nusinersen, which works by changing the splicing of SMN2 pre-mRNA, which increases the quantity of functional SMN protein.
Improved survival rates have allowed children currently undergoing treatment to achieve developmental milestones. This necessitates proactive and multidisciplinary care to manage evolving complications. Among the common concerns for treated children are spinal asymmetries such as scoliosis and kyphosis, which require early and ongoing evaluation.
This study highlights new management approaches including spinal surgery, which is not previously considered for these type 1 SMA patients, and it is essential to develop standardized long-term care plans. Early intervention, regular monitoring, and interdisciplinary collaboration will be crucial in addressing the needs of this growing population and enhancing their quality of life.
References: Abbott L, Main M, Wolfe A, et al. Spinal presentations in children with type 1 spinal muscular atrophy on nusinersen treatment across the SMA-REACH UK network: a retrospective national observational study. BMJ Open. 2025;15(1):e082240. doi:10.1136/bmjopen-2023-082240
